The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of ma...The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administra-tion of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 in-jection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001-0.1 nmol/L had no influence on stage 4 latency (S4L) and sei-zure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all sei-zure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled sei-zures, it had potent anti-convulsant profile and little adverse effects at the dosage of 0.001-0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.展开更多
BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and ...BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and memory.AIM To evaluate the diagnostic value of amygdala on structural magnetic resonance imaging(sMRI)for AD.METHODS In this study,22 patients with AD and 26 controls were enrolled.Their amygdala volumes were measured by sMRI and analyzed using an automatic analysis software.RESULTS The bilateral amygdala volumes of AD patients were significantly lower than those of the controls and were positively correlated with the hippocampal volumes.Receiver operating characteristic curve analyses showed that the sensitivity of the left and right amygdala volumes in diagnosing AD was 80.8%and 88.5%,respectively.Subgroup analyses showed that amygdala atrophy was more serious in AD patients with neuropsychiatric symptoms,which mainly included irritability(22.73%),sleep difficulties(22.73%),apathy(18.18%),and hallucination(13.64%).CONCLUSION Amygdala volumes measured by sMRI can be used to diagnose AD,and amygdala atrophy is more serious in patients with neuropsychiatric symptoms.展开更多
AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotr...AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid(GABA)(1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level(0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA(0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg(1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg(2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg(1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg(noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg(noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg(noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest increased release of inhibitory amino acids by the hippocampus and an increased utilization rate of monoamines by the amygdala after different doses of ayahuasca ingestion.展开更多
AIM: To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects.METHODS: Magnetic resonance imaging was performed on ten patients with vaginismus and ten control sub...AIM: To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects.METHODS: Magnetic resonance imaging was performed on ten patients with vaginismus and ten control subjects matched for age and gender. Volumes of the hippocampus and amygdala were blindly measured. RESULTS: We found that the mean right amygdala volume of patients with vaginismus were smaller than that of the healthy controls. With regard to hippocampus volumes, the mean left and right hippocampus volumes were smaller than those of the healthy controls. CONCLUSION: Our present findings suggest that there have been hippocampus and amygdala structural abnormalities in patients with vaginismus. These changes provide the notion that vaginismus may be a fear-related condition.展开更多
Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorde...Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders.Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in humans.Here we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA populations.Sequencing of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and Adora2a.Direct pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.展开更多
This study was aimed to determine the effect of amygdaline inactivation on the sexual motivation of male rats during a T-maze task with a sexual reward. Subjects were chronically implanted with two stainless-steel can...This study was aimed to determine the effect of amygdaline inactivation on the sexual motivation of male rats during a T-maze task with a sexual reward. Subjects were chronically implanted with two stainless-steel cannulae that enabled the infusion of tetrodotoxin, a sodium channel blocker, into the left and right basolateral amygdala (BLA). Animals were divided into 3 groups: saline (SS);TTX1 (tetrodotoxin at 2.5 ng);and TTX2 (tetrodotoxin at 5.0 ng). To induce a sexually-motivated state, all male rats were allowed to have an intromission with a receptive female before performing the T-maze task, after which their sexual motivation was evaluated during seven trials in which a receptive female was placed in one goal-box of the T-maze, and a non-receptive one in the other. Subjects were allowed an intromission as a sexual reward whenever they reached the goal-box containing the receptive female, but were returned to the start-box if they did not. At the end of the experiment, copulation until ejaculation was permitted. Both doses of TTX increased the time rats required to cross the maze stem during the final trials. In terms of sexual interaction, the high dose of TTX increased more markedly mount, intromission and ejaculation latencies and the number of mounts and intromissions. Overall, these results indicate that the BLA may play an important role in modulating sexual behavior, particularly in maintaining sexual motivation in successive trials in a T-maze task and during sexual interaction per se.展开更多
This study evaluated whether the administration of a NSAID, sodium diclofenac, can promote alterations in the expression of Fos protein in central amygdala (CEA) and the lateral hypothalamus (LH) after 6 h of experime...This study evaluated whether the administration of a NSAID, sodium diclofenac, can promote alterations in the expression of Fos protein in central amygdala (CEA) and the lateral hypothalamus (LH) after 6 h of experimental tooth movement with a controlled force of 70 g, applied to the superior central incisors of rats. Adult male rats were anesthetized and divided into four groups: Control, no orthodontic appliance (OA);OA activated with 70 g;OA activated with 70 g and pretreated with diclofenac sodium (5 mg/kg, intramuscular);and diclofenac sodium alone. Six hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing the CEA and LH were processed for Fos protein immunohistochemistry. The results show that in the control group, intramuscular injection of a ketamine/xylazine mixture did not induce IR-Fos cells in the CEA or LH. However, in the 70 g group, IR-Fos was the strongest observed展开更多
The rat posterodorsal medial amygdala (MePD) is responsive to the orexigenic neuropeptide Y (NPY) and is a putative candidate to participate in neural circuits that modulate feeding behavior. Here, we studied the effe...The rat posterodorsal medial amygdala (MePD) is responsive to the orexigenic neuropeptide Y (NPY) and is a putative candidate to participate in neural circuits that modulate feeding behavior. Here, we studied the effects of intracerebroventricular (icv) microinjection of NPY on the appetitive and food intake behaviors of rats under the paradigm of the self-selection macronutrient isolated diets [high-carbohydrate (high-CHO), high-protein and high-lipid food pellets]. At the same time, Fos expression was also evaluated in the MePD as a marker of local cellular activation. Adult male rats received icv microinjections of NPY (1mg and10mg/5mL, n = 10 and 8, respectively) whereas the control groups either received icv microinjection of artificial cerebrospinal fluid (5mL, n = 8) or underwent sham procedure (n = 8). The data were obtained after a fasting protocol. Feeding behavior was evaluated during a 2 h test period of free access to the selective diets. Rats in all groups preferred the high-CHO diet. Compared to controls, both doses of NPY increased the appetitive behaviors (searching for food and the frequency of attempts to eat any diet) and the percentage of animals eating high-CHO diet. However, only NPY at a dose of 1 μg led to a significant increase in food intake and showed a strong positive correlation with Fos expression in the MePD (p 0.05 in all cases). These new data reveal a biphasic effect of NPY on the appetite and food intake behaviors and suggest that the MePD participates in the NPY-induced feeding behavior in rats.展开更多
The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-an...The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-anxiety (HA) and low-anxiety (LA) rats subjected to the elevated plus-maze (EPM) test was investigated. Anxiolytic-like effects (increase of open-arm entries and open-arm time) was revealed only after administration of muscimol into the left (but not right) amygdala of HA animals. No effect was observed upon administration of muscimol to LA rats. These findings suggest an important role in anxiety regulation of the amygdalar GABA levels, and the assumed GABA hemispheric lateralization.展开更多
Objective To explore the role of phosphodiesterase-2 activity in the amygdala produces anxiolytic-like effects in mice.Methods:Male ICR mice were implanted with guide cannula targeting the central nucleus of the amygd...Objective To explore the role of phosphodiesterase-2 activity in the amygdala produces anxiolytic-like effects in mice.Methods:Male ICR mice were implanted with guide cannula targeting the central nucleus of the amygdala bilaterally.Following recovery from surgery,mice were administered either Bay 60-7550 or lentiviral vector/microRNA targeted to PDE2.The effects of pharmacological inhibition were assessed 30 min post-treatment while those of PDE2 knockdown were assessed beginning one week after treatment with the lentiviral vector/microRNA.Behavioral effects were assessed in the elevated plus-maze and the tail-suspension tests;ODQ was used to assess cyclic GMP involvement.Cannula placement and viral vector localization were determined histologically via its GFP tag.Results:Administration of Bay 60-7550 into the central nucleus of the amygdala resulted in anxiolytic-and antidepressant-like effects on behavior of mice in the elevated plus-maze and tail-suspension test,respectively;these effects were blocked by pretreatment with ODQ.Viral vector/microRNA-induced knockdown of PDE2 resulted in similar effects on behavior in these tests,which also were blocked by ODQ.The treatment reduced PDE2 expression by approximately 80%.Conclusion:The present study does provide an additional line of support that reduced PDE2 activity,achieved in this case via lentiviral vector/microRNA-induced knockdown,is associated with such behavioral effects,resulting from treatment with NO donors,which also increase cyclic GMP signaling.展开更多
Corticotropin-releasing factor (CRF) is a peptide that is released from the hypothalamus into widespread areas of the brain. Evidence has suggested that CRF is involved as a neuromodulator outside of the hypothalamic-...Corticotropin-releasing factor (CRF) is a peptide that is released from the hypothalamus into widespread areas of the brain. Evidence has suggested that CRF is involved as a neuromodulator outside of the hypothalamic-pituitary-adrenal axis, playing an important role in fear, anxiety, depression and pain modulation. Our previous report demonstrated that CRF receptor activation in basolateral (BLA) or central nuclei of the amygdala (CeA) produces innate fear in guinea pigs. Inhibition of these receptors via administration of α-helical CRF9-41 (a nonspecific antagonist) into the CeA or BLA decreased innate fear behavior [1]. Additionally, there is strong evidence that emotional behavior and nociception can be modulated simultaneously. The present study was conducted to investigate the involvement of the CRF receptors of the BLA or CeA in nociception in guinea pigs. Guinea pigs were treated with CRF and α-helical CRF>9-41> in three different doses or injected with α-helical CRF9-41 preceded by CRF into the BLA or CeA, and they were evaluated using the hot plate test. Our findings indicated that activation of CRF receptors in the BLA and in the CeA promoted antinociception, and this effect was reversed by preadministration of α-helical CRF9-41 in the same area. The treatment with α-helical CRF>9-41> per se into the BLA and CeA did not alter nociception. Thus, nociception modulation occurs in a phasic manner, whereas defensive behavior can occur tonically because the α-helical CRF9-41 did not cause any modification on the index of analgesia in the hot plate test but did reduce innate fear behavior [1].展开更多
Fos immunohistochemistry and NADPH-d histochemistry and double labeling of the 2 methods were used to study therelationship between c-Fos expressed neurons and NADPH-d positive neurons of the amygdala in soman-induced...Fos immunohistochemistry and NADPH-d histochemistry and double labeling of the 2 methods were used to study therelationship between c-Fos expressed neurons and NADPH-d positive neurons of the amygdala in soman-induced seizures in the rat.It was found that protooncogene c-fos was overexpressed in the amygdala from 1.5 h to 2 d after soman-induced seizures occurred.c-fos overexpression was in the persisting and delayed pattem. The distribution of Fos immunoreactively positive neurons was sub-nuclear specific. About 10% of the Fos-positive neurons were NADPH-d positive and almost all the NADPH-d positive neuronswere also stained with Fos immunohistochemistry. Our findings together with those reported in our previous paper in which c-fosexpression and NOS activation were found to share the common upstream of the intracellular signal transducing cascade mediatedthrough NMDA receptor depended Ca2+ influx suggest that c-fos expression and nitric oxide neurotoxicity mighy exist in the amygdala lesions after soman induced seizures occurred.展开更多
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied.However,the mechanism whereby local ischemia in deep brain region affect brain functions is stil...Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied.However,the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown.Here,we first established a mini-stroke model by infusion of endothelin-1(ET-1) into the dorsal hippocampus or the lateral amygdala,and then investigated how these mini-infarcts affected brain functions associated with these regions.We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory,but not in learning process and recall of tone fear memory.In novel object task,ET-1 in the hippocampus also eliminated object identity memory.ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear,but did not impair retention of contextual fear.These findings suggest that ET-1-induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.展开更多
Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the ...Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the amygdala in adult SD rats was detected by immunohistochemistry methods,and the duodenal interdigestive MMC was recorded via the electrodes implanted in the duodenum and analyzed us- ing a multichannel recorder.Results:Motilin receptor was observed in the amygdala of rats.The great amount of motilin receptor was found in the medial amygdaloid nucleus,which was also abundant in the basolateral nucleus but less abundant in the basomedial amygdaloid nucleus,the central amygdaloid nucle- us and the lateral amygdaloid nucleus.The shortening of the duodenal MMC cycle duration and the in- crease of the amplitude and the frequency of phase $ were recorded after motilin receptors being bound with exogenous motilin in the amygdala.The effects could be completely blocked by the subdiaphragmatic vagotomy but not by the intravenous injections of atropine,phentolamine or propranolol.Anti-motilin serum could partially block these effects,and the destruction of the basolateral nucleus of the amygdala had no significant effects on the duodenal MMC.Conclusion:Motilin receptor is present in all the subnu- clei of the amygdala,with the greatest amount of motilin receptor present in the medial amygdaloid nucle- us.Microinjections of motilin in the amygdala can shorten the duodenal MMC cycle duration and increase the amplitude and the frequency of phaseⅢ.These effects might be accomplished via the amygdala-hy- pothalamus-brainstem-vagus pathway,indicating the important role of the amygdala motilin receptor in the duodenal MMC regulation.展开更多
In order to explore the MRI volume of the amygdala and hippocampus in patients with major depression, quantitative MRI of the amygdala and hippocampus were studied in 22 patients with major depression and compared wit...In order to explore the MRI volume of the amygdala and hippocampus in patients with major depression, quantitative MRI of the amygdala and hippocampus were studied in 22 patients with major depression and compared with 13 age-matched controls. The results showed that both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The volume of the bilateral hippocampus was significantly smaller in the major depression group than that in control group. The patients had significant asymmetry of the amygdalar volumes (right smaller than left). No correlation was found between hippocampal volume abnormalities and ill duration. It was concluded that the hippocampus and amygdala within limbic-cortical networks may play a crucial role in the pathogenesis of major depression.展开更多
Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures. We hypothesized that the expression of the brain water channel aq-uaporin-4 (AQP-4) may be upregulat...Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures. We hypothesized that the expression of the brain water channel aq-uaporin-4 (AQP-4) may be upregulated in the epileptic brain. In the present study, we estab-lished the amygdala kindling model of epilepsy, and quantified AQP-4 protein and mRNA levels, using reverse transcription-PCR, immunohistochemistry and western blotting, in epileptic and control rats. We found that AQP-4 was overexpressed in the cerebral cortex of rats with epi-lepsy compared with controls. These findings show that AQP-4 is highly expressed in the brain of amygdala-kindled rats, suggesting that repeated seizures affect water homeostasis in the brain.展开更多
Background:Childhood maltreatment(CM)is a potential risk factor for some neuropsychiatric disorders in adulthood(e.g.depression and anxiety)and alters trajectories of brain development.Accumulating evidence suggests t...Background:Childhood maltreatment(CM)is a potential risk factor for some neuropsychiatric disorders in adulthood(e.g.depression and anxiety)and alters trajectories of brain development.Accumulating evidence suggests that functional connectivity of the limbic system,especially the amygdala,is highly associated with childhood maltreatment,although not all studies have found this.These inconsistent results may be due to differential alterations of amygdala resting-state functional connectivity(rsFC)following childhood maltreatment.Objective:Our aim was to investigate the relationship between the rsFC of amygdala subregions and CM severity,as well as to develop a stable rsFC-based model for inferring the severity of CM.Methods:In this study,we employed the Childhood Trauma Questionnaire(CTQ)to assess CM severity in each individual.We explored the relationship between the rsFC of amygdala subregions(i.e.centromedial-CMA,basolateral-BLA,superficial-SFA amygdala)and CM experience in a discovery dataset of n=110 healthy Chinese participants by linear multiple regression analysis.Subsequent dimensional and categorical approach were performed to elucidate the relationship between rsFCs and CM severity and CM subtypes,respectively.A support vector regression model was then conducted to validate the associations between rsFCs and total CTQ scores.Moreover,we also verified the model into another independent replication dataset(n=38).Results:Our findings suggested that childhood maltreatment was negatively associated with rsFC between the right superficial amyg-dala and perigenual anterior cingulate cortex(pgACC)/postcentral gyrus(PCG)but not the other two amygdala subregions.Moreover,SFA-pgACC coupling was more associated with physical neglect whereas the SFA-PCG was more related to emotional neglect.In addi-tion,supervised machine learning confirmed that using these two rsFCs as predictors could stably estimate continuous maltreatment severity in both discovery and replication datasets.Conclusion:The current study supports that the rsFCs of superficial amygdala are related to childhood maltreatment and which may be a potential biomarker for the effects of childhood maltreatment-related psychiatric disorders(i.e.depression and anxiety).展开更多
Background:Amygdala plays an important role in the neurobiological basis of panic disorder(PD),and the amygdala contains different subregions,which may play different roles in PD.The aim of the present study was to ex...Background:Amygdala plays an important role in the neurobiological basis of panic disorder(PD),and the amygdala contains different subregions,which may play different roles in PD.The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest(ROIs)and the clinical symptoms of PD patients.Methods:Fifty-three drug-naïve,non-comorbid PD patients and 70 healthy controls(HCs)were recruited.Seed-based resting-state functional connectivity(rsFC)analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed.Two samples t test was performed for the seed-based Fisher's z-transformed correlation maps.The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis.Results:PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group(left amygdala[lAMY]:t=4.84,P<0.001;right amygdala[rAMY]:t=4.55,P<0.001;left centromedial amygdala[lCMA]:t=3.87,P<0.001;right centromedial amygdala[rCMA]:t=3.82,P=0.002;left laterobasal amygdala[lBLA]:t=4.33,P<0.001;right laterobasal amygdala[rBLA]:t=4.97,P<0.001;left superficial amygdala[lSFA]:t=3.26,P=0.006).The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group(t=3.70,P=0.003).And most of the altered rsFCs were located in the default mode network(DMN).A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients(r=0.285,P=0.039).Conclusions:Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD.Future studies may further explore whether the rsFC of amygdala subregions,especially with the regions in DMN,can be used as a biological marker of PD.展开更多
The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regul...The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.展开更多
OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxi...OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.展开更多
基金supported by a grant from the National Natural Science Foundation of China(No.30770752)
文摘The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administra-tion of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 in-jection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001-0.1 nmol/L had no influence on stage 4 latency (S4L) and sei-zure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all sei-zure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001-0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled sei-zures, it had potent anti-convulsant profile and little adverse effects at the dosage of 0.001-0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.
基金Supported by The Young Talents Fund of the Second Hospital of Shandong University,No.2018YT16Rongxiang Regenerative Medicine Foundation of Shandong University,No.2019SDRX-09.
文摘BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and memory.AIM To evaluate the diagnostic value of amygdala on structural magnetic resonance imaging(sMRI)for AD.METHODS In this study,22 patients with AD and 26 controls were enrolled.Their amygdala volumes were measured by sMRI and analyzed using an automatic analysis software.RESULTS The bilateral amygdala volumes of AD patients were significantly lower than those of the controls and were positively correlated with the hippocampal volumes.Receiver operating characteristic curve analyses showed that the sensitivity of the left and right amygdala volumes in diagnosing AD was 80.8%and 88.5%,respectively.Subgroup analyses showed that amygdala atrophy was more serious in AD patients with neuropsychiatric symptoms,which mainly included irritability(22.73%),sleep difficulties(22.73%),apathy(18.18%),and hallucination(13.64%).CONCLUSION Amygdala volumes measured by sMRI can be used to diagnose AD,and amygdala atrophy is more serious in patients with neuropsychiatric symptoms.
基金Supported by Funda o de Amparo a Pesquisa do Estado de S o PauloCoordena o de Aperfei oamento de Pessoal de Nível Superior+1 种基金Conselho Nacional de Desenvolvimento Científico e TecnológicoInstituto Nacional de Neurociência Translacional
文摘AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid(GABA)(1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level(0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA(0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg(1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg(2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg(1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg(noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg(noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg(noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest increased release of inhibitory amino acids by the hippocampus and an increased utilization rate of monoamines by the amygdala after different doses of ayahuasca ingestion.
文摘AIM: To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects.METHODS: Magnetic resonance imaging was performed on ten patients with vaginismus and ten control subjects matched for age and gender. Volumes of the hippocampus and amygdala were blindly measured. RESULTS: We found that the mean right amygdala volume of patients with vaginismus were smaller than that of the healthy controls. With regard to hippocampus volumes, the mean left and right hippocampus volumes were smaller than those of the healthy controls. CONCLUSION: Our present findings suggest that there have been hippocampus and amygdala structural abnormalities in patients with vaginismus. These changes provide the notion that vaginismus may be a fear-related condition.
文摘Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders.Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in humans.Here we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA populations.Sequencing of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and Adora2a.Direct pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.
文摘This study was aimed to determine the effect of amygdaline inactivation on the sexual motivation of male rats during a T-maze task with a sexual reward. Subjects were chronically implanted with two stainless-steel cannulae that enabled the infusion of tetrodotoxin, a sodium channel blocker, into the left and right basolateral amygdala (BLA). Animals were divided into 3 groups: saline (SS);TTX1 (tetrodotoxin at 2.5 ng);and TTX2 (tetrodotoxin at 5.0 ng). To induce a sexually-motivated state, all male rats were allowed to have an intromission with a receptive female before performing the T-maze task, after which their sexual motivation was evaluated during seven trials in which a receptive female was placed in one goal-box of the T-maze, and a non-receptive one in the other. Subjects were allowed an intromission as a sexual reward whenever they reached the goal-box containing the receptive female, but were returned to the start-box if they did not. At the end of the experiment, copulation until ejaculation was permitted. Both doses of TTX increased the time rats required to cross the maze stem during the final trials. In terms of sexual interaction, the high dose of TTX increased more markedly mount, intromission and ejaculation latencies and the number of mounts and intromissions. Overall, these results indicate that the BLA may play an important role in modulating sexual behavior, particularly in maintaining sexual motivation in successive trials in a T-maze task and during sexual interaction per se.
文摘This study evaluated whether the administration of a NSAID, sodium diclofenac, can promote alterations in the expression of Fos protein in central amygdala (CEA) and the lateral hypothalamus (LH) after 6 h of experimental tooth movement with a controlled force of 70 g, applied to the superior central incisors of rats. Adult male rats were anesthetized and divided into four groups: Control, no orthodontic appliance (OA);OA activated with 70 g;OA activated with 70 g and pretreated with diclofenac sodium (5 mg/kg, intramuscular);and diclofenac sodium alone. Six hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing the CEA and LH were processed for Fos protein immunohistochemistry. The results show that in the control group, intramuscular injection of a ketamine/xylazine mixture did not induce IR-Fos cells in the CEA or LH. However, in the 70 g group, IR-Fos was the strongest observed
文摘The rat posterodorsal medial amygdala (MePD) is responsive to the orexigenic neuropeptide Y (NPY) and is a putative candidate to participate in neural circuits that modulate feeding behavior. Here, we studied the effects of intracerebroventricular (icv) microinjection of NPY on the appetitive and food intake behaviors of rats under the paradigm of the self-selection macronutrient isolated diets [high-carbohydrate (high-CHO), high-protein and high-lipid food pellets]. At the same time, Fos expression was also evaluated in the MePD as a marker of local cellular activation. Adult male rats received icv microinjections of NPY (1mg and10mg/5mL, n = 10 and 8, respectively) whereas the control groups either received icv microinjection of artificial cerebrospinal fluid (5mL, n = 8) or underwent sham procedure (n = 8). The data were obtained after a fasting protocol. Feeding behavior was evaluated during a 2 h test period of free access to the selective diets. Rats in all groups preferred the high-CHO diet. Compared to controls, both doses of NPY increased the appetitive behaviors (searching for food and the frequency of attempts to eat any diet) and the percentage of animals eating high-CHO diet. However, only NPY at a dose of 1 μg led to a significant increase in food intake and showed a strong positive correlation with Fos expression in the MePD (p 0.05 in all cases). These new data reveal a biphasic effect of NPY on the appetite and food intake behaviors and suggest that the MePD participates in the NPY-induced feeding behavior in rats.
文摘The influence of γ-aminobutyric type-A (GABA<sub>A</sub>) receptors agonist (muscimol hydrobromide, 0.1 μg/0.5 μl) injections into the right or left basolateral amygdala (BLA) on the behavior of high-anxiety (HA) and low-anxiety (LA) rats subjected to the elevated plus-maze (EPM) test was investigated. Anxiolytic-like effects (increase of open-arm entries and open-arm time) was revealed only after administration of muscimol into the left (but not right) amygdala of HA animals. No effect was observed upon administration of muscimol to LA rats. These findings suggest an important role in anxiety regulation of the amygdalar GABA levels, and the assumed GABA hemispheric lateralization.
文摘Objective To explore the role of phosphodiesterase-2 activity in the amygdala produces anxiolytic-like effects in mice.Methods:Male ICR mice were implanted with guide cannula targeting the central nucleus of the amygdala bilaterally.Following recovery from surgery,mice were administered either Bay 60-7550 or lentiviral vector/microRNA targeted to PDE2.The effects of pharmacological inhibition were assessed 30 min post-treatment while those of PDE2 knockdown were assessed beginning one week after treatment with the lentiviral vector/microRNA.Behavioral effects were assessed in the elevated plus-maze and the tail-suspension tests;ODQ was used to assess cyclic GMP involvement.Cannula placement and viral vector localization were determined histologically via its GFP tag.Results:Administration of Bay 60-7550 into the central nucleus of the amygdala resulted in anxiolytic-and antidepressant-like effects on behavior of mice in the elevated plus-maze and tail-suspension test,respectively;these effects were blocked by pretreatment with ODQ.Viral vector/microRNA-induced knockdown of PDE2 resulted in similar effects on behavior in these tests,which also were blocked by ODQ.The treatment reduced PDE2 expression by approximately 80%.Conclusion:The present study does provide an additional line of support that reduced PDE2 activity,achieved in this case via lentiviral vector/microRNA-induced knockdown,is associated with such behavioral effects,resulting from treatment with NO donors,which also increase cyclic GMP signaling.
基金supported by CAPES/PROEX,FAPESP(2010/10936-5)A.F.Donatti has a doctorate scholarship from CAPESC.R.A.Leite-Panissi also received grants from the CNPq(Grant No.307383/2012-1).
文摘Corticotropin-releasing factor (CRF) is a peptide that is released from the hypothalamus into widespread areas of the brain. Evidence has suggested that CRF is involved as a neuromodulator outside of the hypothalamic-pituitary-adrenal axis, playing an important role in fear, anxiety, depression and pain modulation. Our previous report demonstrated that CRF receptor activation in basolateral (BLA) or central nuclei of the amygdala (CeA) produces innate fear in guinea pigs. Inhibition of these receptors via administration of α-helical CRF9-41 (a nonspecific antagonist) into the CeA or BLA decreased innate fear behavior [1]. Additionally, there is strong evidence that emotional behavior and nociception can be modulated simultaneously. The present study was conducted to investigate the involvement of the CRF receptors of the BLA or CeA in nociception in guinea pigs. Guinea pigs were treated with CRF and α-helical CRF>9-41> in three different doses or injected with α-helical CRF9-41 preceded by CRF into the BLA or CeA, and they were evaluated using the hot plate test. Our findings indicated that activation of CRF receptors in the BLA and in the CeA promoted antinociception, and this effect was reversed by preadministration of α-helical CRF9-41 in the same area. The treatment with α-helical CRF>9-41> per se into the BLA and CeA did not alter nociception. Thus, nociception modulation occurs in a phasic manner, whereas defensive behavior can occur tonically because the α-helical CRF9-41 did not cause any modification on the index of analgesia in the hot plate test but did reduce innate fear behavior [1].
文摘Fos immunohistochemistry and NADPH-d histochemistry and double labeling of the 2 methods were used to study therelationship between c-Fos expressed neurons and NADPH-d positive neurons of the amygdala in soman-induced seizures in the rat.It was found that protooncogene c-fos was overexpressed in the amygdala from 1.5 h to 2 d after soman-induced seizures occurred.c-fos overexpression was in the persisting and delayed pattem. The distribution of Fos immunoreactively positive neurons was sub-nuclear specific. About 10% of the Fos-positive neurons were NADPH-d positive and almost all the NADPH-d positive neuronswere also stained with Fos immunohistochemistry. Our findings together with those reported in our previous paper in which c-fosexpression and NOS activation were found to share the common upstream of the intracellular signal transducing cascade mediatedthrough NMDA receptor depended Ca2+ influx suggest that c-fos expression and nitric oxide neurotoxicity mighy exist in the amygdala lesions after soman induced seizures occurred.
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied.However,the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown.Here,we first established a mini-stroke model by infusion of endothelin-1(ET-1) into the dorsal hippocampus or the lateral amygdala,and then investigated how these mini-infarcts affected brain functions associated with these regions.We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory,but not in learning process and recall of tone fear memory.In novel object task,ET-1 in the hippocampus also eliminated object identity memory.ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear,but did not impair retention of contextual fear.These findings suggest that ET-1-induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.
基金The Clinical Speciality Emphasis Topic Foundation of Department of Health(No.2004-56)
文摘Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the amygdala in adult SD rats was detected by immunohistochemistry methods,and the duodenal interdigestive MMC was recorded via the electrodes implanted in the duodenum and analyzed us- ing a multichannel recorder.Results:Motilin receptor was observed in the amygdala of rats.The great amount of motilin receptor was found in the medial amygdaloid nucleus,which was also abundant in the basolateral nucleus but less abundant in the basomedial amygdaloid nucleus,the central amygdaloid nucle- us and the lateral amygdaloid nucleus.The shortening of the duodenal MMC cycle duration and the in- crease of the amplitude and the frequency of phase $ were recorded after motilin receptors being bound with exogenous motilin in the amygdala.The effects could be completely blocked by the subdiaphragmatic vagotomy but not by the intravenous injections of atropine,phentolamine or propranolol.Anti-motilin serum could partially block these effects,and the destruction of the basolateral nucleus of the amygdala had no significant effects on the duodenal MMC.Conclusion:Motilin receptor is present in all the subnu- clei of the amygdala,with the greatest amount of motilin receptor present in the medial amygdaloid nucle- us.Microinjections of motilin in the amygdala can shorten the duodenal MMC cycle duration and increase the amplitude and the frequency of phaseⅢ.These effects might be accomplished via the amygdala-hy- pothalamus-brainstem-vagus pathway,indicating the important role of the amygdala motilin receptor in the duodenal MMC regulation.
文摘In order to explore the MRI volume of the amygdala and hippocampus in patients with major depression, quantitative MRI of the amygdala and hippocampus were studied in 22 patients with major depression and compared with 13 age-matched controls. The results showed that both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The volume of the bilateral hippocampus was significantly smaller in the major depression group than that in control group. The patients had significant asymmetry of the amygdalar volumes (right smaller than left). No correlation was found between hippocampal volume abnormalities and ill duration. It was concluded that the hippocampus and amygdala within limbic-cortical networks may play a crucial role in the pathogenesis of major depression.
基金the Natural Science Foundation of Shanghai, No. 09ZR1405500the Research Projects of Shanghai Municipal Health Bureau, No. 2008-08
文摘Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures. We hypothesized that the expression of the brain water channel aq-uaporin-4 (AQP-4) may be upregulated in the epileptic brain. In the present study, we estab-lished the amygdala kindling model of epilepsy, and quantified AQP-4 protein and mRNA levels, using reverse transcription-PCR, immunohistochemistry and western blotting, in epileptic and control rats. We found that AQP-4 was overexpressed in the cerebral cortex of rats with epi-lepsy compared with controls. These findings show that AQP-4 is highly expressed in the brain of amygdala-kindled rats, suggesting that repeated seizures affect water homeostasis in the brain.
基金supported by the Fundamental Research Funds for the Central Universities,UESTC[grant number ZYGX2020J027-WHZ]Natural Science Foundation of sichuan Province[grant number 2022NSFSC1375-WHZ]+1 种基金Guangdong Basic and Applied Basic Research Foundation[grant number 2021A1515110511-WHZ]Sichuan Science and Technology Program[grant number 2020YFS0484 WXY].
文摘Background:Childhood maltreatment(CM)is a potential risk factor for some neuropsychiatric disorders in adulthood(e.g.depression and anxiety)and alters trajectories of brain development.Accumulating evidence suggests that functional connectivity of the limbic system,especially the amygdala,is highly associated with childhood maltreatment,although not all studies have found this.These inconsistent results may be due to differential alterations of amygdala resting-state functional connectivity(rsFC)following childhood maltreatment.Objective:Our aim was to investigate the relationship between the rsFC of amygdala subregions and CM severity,as well as to develop a stable rsFC-based model for inferring the severity of CM.Methods:In this study,we employed the Childhood Trauma Questionnaire(CTQ)to assess CM severity in each individual.We explored the relationship between the rsFC of amygdala subregions(i.e.centromedial-CMA,basolateral-BLA,superficial-SFA amygdala)and CM experience in a discovery dataset of n=110 healthy Chinese participants by linear multiple regression analysis.Subsequent dimensional and categorical approach were performed to elucidate the relationship between rsFCs and CM severity and CM subtypes,respectively.A support vector regression model was then conducted to validate the associations between rsFCs and total CTQ scores.Moreover,we also verified the model into another independent replication dataset(n=38).Results:Our findings suggested that childhood maltreatment was negatively associated with rsFC between the right superficial amyg-dala and perigenual anterior cingulate cortex(pgACC)/postcentral gyrus(PCG)but not the other two amygdala subregions.Moreover,SFA-pgACC coupling was more associated with physical neglect whereas the SFA-PCG was more related to emotional neglect.In addi-tion,supervised machine learning confirmed that using these two rsFCs as predictors could stably estimate continuous maltreatment severity in both discovery and replication datasets.Conclusion:The current study supports that the rsFCs of superficial amygdala are related to childhood maltreatment and which may be a potential biomarker for the effects of childhood maltreatment-related psychiatric disorders(i.e.depression and anxiety).
基金Capital’s Funds for Health Improvement and Research(No.2020-1-2121)Beijing Municipal Science and Technology Commission(No.Z181100001718077)Special Funding of the Beijing Municipal Administration of Hospitals Clinical Medicine Development(No.ZYLX201815)
文摘Background:Amygdala plays an important role in the neurobiological basis of panic disorder(PD),and the amygdala contains different subregions,which may play different roles in PD.The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest(ROIs)and the clinical symptoms of PD patients.Methods:Fifty-three drug-naïve,non-comorbid PD patients and 70 healthy controls(HCs)were recruited.Seed-based resting-state functional connectivity(rsFC)analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed.Two samples t test was performed for the seed-based Fisher's z-transformed correlation maps.The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis.Results:PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group(left amygdala[lAMY]:t=4.84,P<0.001;right amygdala[rAMY]:t=4.55,P<0.001;left centromedial amygdala[lCMA]:t=3.87,P<0.001;right centromedial amygdala[rCMA]:t=3.82,P=0.002;left laterobasal amygdala[lBLA]:t=4.33,P<0.001;right laterobasal amygdala[rBLA]:t=4.97,P<0.001;left superficial amygdala[lSFA]:t=3.26,P=0.006).The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group(t=3.70,P=0.003).And most of the altered rsFCs were located in the default mode network(DMN).A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients(r=0.285,P=0.039).Conclusions:Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD.Future studies may further explore whether the rsFC of amygdala subregions,especially with the regions in DMN,can be used as a biological marker of PD.
基金supported by the Zhejiang Province Natural Science Foundation of China(LD22H090003)Key-Area Research and Development Program of Guangdong Province(2019B030335001 and 2018B030334001)+3 种基金the National Natural Science Foundation of China(31871070,82090031,32071097,31871056,and 32170991)the Key R&D Program of Zhejiang Province(2020C03009)Fundamental Research Funds for the Central Universities(2021FZZX001-37)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057).
文摘The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.
基金Supported by the National Natural Science Foundation of China:Study on the Mechanism of Suspension Moxibustion with Moxa Stick in Treating Hydrocortisone Rats with Kidney-Yang Deficiency based on Hippocampus(amygdala)-HPA Axis(No.81660817)。
文摘OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.
