Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
The catecholamine,dopamine,plays an important role in the central nervous system of mammals,including executive functions,motor control,motivation,arousal,reinforcement,and reward.Dysfunctions of the dopaminergic syst...The catecholamine,dopamine,plays an important role in the central nervous system of mammals,including executive functions,motor control,motivation,arousal,reinforcement,and reward.Dysfunctions of the dopaminergic system lead to diseases of the brains,such as Parkinson’s disease,Tourette’s syndrome,and schizophrenia.In addition to its fundamental role as a neurotransmitter,there is evidence for a role as a growth differentiation factor during development.Recent studies suggest that dopamine regulates the development ofγ-aminobutyric acidergic interneurons of the cerebral cortex.Moreover,in adult brains,dopamine increases the production of new neurons in the hippocampus,suggesting the promoting effect of dopamine on proliferation and differentiation of neural stem cells and progenitor cells in the adult brains.In this mini-review,I center my attention on dopaminergic functions in the cortical interneurons during development and further discuss cell therapy against neurodegenerative diseases.展开更多
Objective:To investigate the neuromodulatory effect of pinellia total alkaloids(PTA)on the gamma-aminobutyric acidergic(GABAergic)system in epileptic rats,and preliminarily evaluate the anti-epileptic effect of PTA.Me...Objective:To investigate the neuromodulatory effect of pinellia total alkaloids(PTA)on the gamma-aminobutyric acidergic(GABAergic)system in epileptic rats,and preliminarily evaluate the anti-epileptic effect of PTA.Methods:Ninety-one male Sprague-Dawley rats were randomized to a control group(n=17)or an epileptic group(n=74)using computer-generated random numbers.Status epilepticus(SE)was induced with pilocarpine in the epileptic group.Epileptic rats that survived SE were randomly divided into 4 groups,namely an epilepsy group(n=13),a topiramate(TPM,60 mg/kg)group(n=12),a high-dose PTA(800 mg/kg)group(n=12),and a low-dose PTA(400 mg/kg)group(n=10).Treatments were given intragastrically once daily for 14 days.The control group and epilepsy group received normal saline.Spontaneous recurrent seizures(SRSs)were monitored 8-h daily for 7 days after treatment.Then,the hippocampal formation tissues were collected.GABA level was measured using enzyme-linked immunosorbent assay.Protein and mRNA expression levels of glutamate decarboxylase 65(GAD65),GABA transporter-1(GAT-1),GABA transaminase(GABA-T),and GABAA receptor(GABAAR)α4,α5,γ2 andδsubunits were measured using Western-blotting analysis and quantitative polymerase chain reaction.Results:PTA lowered the incidence and frequency of SRS(both doses vs.the TPM group,P>0.05).Compared with the epilepsy group,PTA increased the levels of GABA(both doses P<0.01)and GAD65(mRNA,800 mg/kg,P<0.01),and suppressed the levels of GAT-1(mRNA,800 mg/kg,P<0.01;400 mg/kg,P<0.05),GABA-T(mRNA,both doses P<0.01),and GABAARδsubunit(protein,800 mg/kg,P<0.05)andγ2 subunit(protein,both doses P<0.01).PTA upregulated the low-expressed mRNA levels of GABAARα5 subunit(400 mg/kg,P<0.01),δsubunit(800 mg/kg,P<0.05),andγ2 subunit(400 mg/kg,P<0.05).Conclusions:PTA regulated the GABAergic system through modulating GABA levels and the expression levels of GAD65,GAT-1,GABA-T,and GABAARα4,α5,γ2 andδsubunits.PTA may exert antiepileptic effects on the pilocarpine-induced epilepsy model.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金supported by Japan Society for the Promotion of Science,Grants-in-Aid for Scientific Research [grant number JP17K07084]Takeda Science Foundation
文摘The catecholamine,dopamine,plays an important role in the central nervous system of mammals,including executive functions,motor control,motivation,arousal,reinforcement,and reward.Dysfunctions of the dopaminergic system lead to diseases of the brains,such as Parkinson’s disease,Tourette’s syndrome,and schizophrenia.In addition to its fundamental role as a neurotransmitter,there is evidence for a role as a growth differentiation factor during development.Recent studies suggest that dopamine regulates the development ofγ-aminobutyric acidergic interneurons of the cerebral cortex.Moreover,in adult brains,dopamine increases the production of new neurons in the hippocampus,suggesting the promoting effect of dopamine on proliferation and differentiation of neural stem cells and progenitor cells in the adult brains.In this mini-review,I center my attention on dopaminergic functions in the cortical interneurons during development and further discuss cell therapy against neurodegenerative diseases.
文摘Objective:To investigate the neuromodulatory effect of pinellia total alkaloids(PTA)on the gamma-aminobutyric acidergic(GABAergic)system in epileptic rats,and preliminarily evaluate the anti-epileptic effect of PTA.Methods:Ninety-one male Sprague-Dawley rats were randomized to a control group(n=17)or an epileptic group(n=74)using computer-generated random numbers.Status epilepticus(SE)was induced with pilocarpine in the epileptic group.Epileptic rats that survived SE were randomly divided into 4 groups,namely an epilepsy group(n=13),a topiramate(TPM,60 mg/kg)group(n=12),a high-dose PTA(800 mg/kg)group(n=12),and a low-dose PTA(400 mg/kg)group(n=10).Treatments were given intragastrically once daily for 14 days.The control group and epilepsy group received normal saline.Spontaneous recurrent seizures(SRSs)were monitored 8-h daily for 7 days after treatment.Then,the hippocampal formation tissues were collected.GABA level was measured using enzyme-linked immunosorbent assay.Protein and mRNA expression levels of glutamate decarboxylase 65(GAD65),GABA transporter-1(GAT-1),GABA transaminase(GABA-T),and GABAA receptor(GABAAR)α4,α5,γ2 andδsubunits were measured using Western-blotting analysis and quantitative polymerase chain reaction.Results:PTA lowered the incidence and frequency of SRS(both doses vs.the TPM group,P>0.05).Compared with the epilepsy group,PTA increased the levels of GABA(both doses P<0.01)and GAD65(mRNA,800 mg/kg,P<0.01),and suppressed the levels of GAT-1(mRNA,800 mg/kg,P<0.01;400 mg/kg,P<0.05),GABA-T(mRNA,both doses P<0.01),and GABAARδsubunit(protein,800 mg/kg,P<0.05)andγ2 subunit(protein,both doses P<0.01).PTA upregulated the low-expressed mRNA levels of GABAARα5 subunit(400 mg/kg,P<0.01),δsubunit(800 mg/kg,P<0.05),andγ2 subunit(400 mg/kg,P<0.05).Conclusions:PTA regulated the GABAergic system through modulating GABA levels and the expression levels of GAD65,GAT-1,GABA-T,and GABAARα4,α5,γ2 andδsubunits.PTA may exert antiepileptic effects on the pilocarpine-induced epilepsy model.
