Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to t...Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.展开更多
High-frequency spinal cord stimulation(HF-SCS) has been established as an effective therapy for neuropathic pain. However, the analgesic mechanisms involved in HF-SCS remain to be clarified. In our study, adult rat ne...High-frequency spinal cord stimulation(HF-SCS) has been established as an effective therapy for neuropathic pain. However, the analgesic mechanisms involved in HF-SCS remain to be clarified. In our study, adult rat neuropathic pain was induced by spinal nerve ligation. Two days after modeling, the rats were subjected to 4 hours of HF-SCS(motor threshold 50%, frequency 10,000 Hz, and pulse width 0.024 ms) in the dorsal horn of the spinal cord. The results revealed that the tactile allodynia of spinal nerve-injured rats was markedly alleviated by HFSCS, and the effects were sustained for 3 hours after the stimulation had ceased. HF-SCS restored lysosomal function, increased the levels of lysosome-associated membrane protein 2(LAMP2) and the mature form of cathepsin D(matu-CTSD), and alleviated the abnormally elevated levels of microtubule-associated protein 1 A/B-light chain 3(LC3)-II and sequestosome 1(P62) in spinal nerve-injured rats. HF-SCS also mostly restored the immunoreactivity of LAMP2, which was localized in neurons in the superficial layers of the spinal dorsal horn in spinal nerve-injured rats. In addition, intraperitoneal administration of 15 mg/kg chloroquine for 60 minutes reversed the expression of the aforementioned proteins and shortened the timing of the analgesic effects of HF-SCS. These findings suggest that HF-SCS may exhibit longlasting analgesic effects on neuropathic pain in rats through improving lysosomal dysfunction and alleviating autophagic flux. This study was approved by the Laboratory Animal Ethics Committee of China Medical University, Shenyang, China(approval No. 2017 PS196 K) on March 1, 2017.展开更多
BACKGROUND Cognitive impairments are core characteristics of schizophrenia,but are largely resistant to current treatments.Several recent studies have shown that highfrequency repetitive transcranial magnetic stimulat...BACKGROUND Cognitive impairments are core characteristics of schizophrenia,but are largely resistant to current treatments.Several recent studies have shown that highfrequency repetitive transcranial magnetic stimulation(rTMS)of the left dorsolateral prefrontal cortex(DLPFC)can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients.However,results are inconsistent across studies.AIM To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia.METHODS Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC(n=25)or sham stimulation(n=22)on weekdays for four consecutive weeks.Patients performed the pattern recognition memory(PRM)task from the Cambridge Neuropsychological Test Automated Battery at baseline,at the end of rTMS treatment(week 4),and 4 wk after rTMS treatment(week 8).Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms(SANS)and the Positive and Negative Syndrome Scale(PANSS).RESULTS There were no significant differences in PRM performance metrics,SANS total score,SANS subscores,PANSS total score,and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period,but PRM performance metrics(percent correct and number correct)and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group(all P<0.05).Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment.Moreover,the improvement in visual memory was correlated with the reduction in negative symptoms at week 8.In contrast,there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8(all P>0.05).CONCLUSION High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia,but these effects are delayed,potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.展开更多
Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the ex...Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex(M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.展开更多
Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,...Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.展开更多
基金the scope of the CICS-UBI projects UIDP/Multi/00709/2019,UIDB/Multi/00709/2019,UIDP/00709/2020,UIDB/00709/2020,financed by national funds through the Portuguese Foundation for Science and Technology/MCTESby funds to the PPBI-Portuguese Platform of Bio Imaging through the Project POCI-01-0145-FEDER-022122(to GB,MVP,NP)supported by a grant from the Portuguese Foundation for Science and Technology/MCTES(2021.07854.BD)(to IS)。
文摘Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.
基金supported by the National Nature Science Foundation of China,No.81870838Liaoning Province Distinguished Professor Support Program of China,No.XLYC1802096+1 种基金Shenyang Clinical Medicine Research Center of Anesthesiology of China,Nos.19-110-4-24,20-204-4-44the Outstanding Scientific Foundation of Shengjing Hospital of China,No.201708(all to PZ)。
文摘High-frequency spinal cord stimulation(HF-SCS) has been established as an effective therapy for neuropathic pain. However, the analgesic mechanisms involved in HF-SCS remain to be clarified. In our study, adult rat neuropathic pain was induced by spinal nerve ligation. Two days after modeling, the rats were subjected to 4 hours of HF-SCS(motor threshold 50%, frequency 10,000 Hz, and pulse width 0.024 ms) in the dorsal horn of the spinal cord. The results revealed that the tactile allodynia of spinal nerve-injured rats was markedly alleviated by HFSCS, and the effects were sustained for 3 hours after the stimulation had ceased. HF-SCS restored lysosomal function, increased the levels of lysosome-associated membrane protein 2(LAMP2) and the mature form of cathepsin D(matu-CTSD), and alleviated the abnormally elevated levels of microtubule-associated protein 1 A/B-light chain 3(LC3)-II and sequestosome 1(P62) in spinal nerve-injured rats. HF-SCS also mostly restored the immunoreactivity of LAMP2, which was localized in neurons in the superficial layers of the spinal dorsal horn in spinal nerve-injured rats. In addition, intraperitoneal administration of 15 mg/kg chloroquine for 60 minutes reversed the expression of the aforementioned proteins and shortened the timing of the analgesic effects of HF-SCS. These findings suggest that HF-SCS may exhibit longlasting analgesic effects on neuropathic pain in rats through improving lysosomal dysfunction and alleviating autophagic flux. This study was approved by the Laboratory Animal Ethics Committee of China Medical University, Shenyang, China(approval No. 2017 PS196 K) on March 1, 2017.
基金Supported by Key Diagnosis and Treatment Program of Suzhou,No.LCZX201919 and No.LCZX202016The Scientific and Technological Program of Suzhou,No.SS201752 and No.SS202069Introduction Project of Suzhou Clinical Expert Team,No.SZYJTD201715。
文摘BACKGROUND Cognitive impairments are core characteristics of schizophrenia,but are largely resistant to current treatments.Several recent studies have shown that highfrequency repetitive transcranial magnetic stimulation(rTMS)of the left dorsolateral prefrontal cortex(DLPFC)can reduce negative symptoms and improve certain cognitive deficits in schizophrenia patients.However,results are inconsistent across studies.AIM To examine if high-frequency rTMS of the DLPFC can improve visual memory deficits in patients with schizophrenia.METHODS Forty-seven chronic schizophrenia patients with severe negative symptoms on stable treatment regimens were randomly assigned to receive active rTMS to the DLPFC(n=25)or sham stimulation(n=22)on weekdays for four consecutive weeks.Patients performed the pattern recognition memory(PRM)task from the Cambridge Neuropsychological Test Automated Battery at baseline,at the end of rTMS treatment(week 4),and 4 wk after rTMS treatment(week 8).Clinical symptoms were also measured at these same time points using the Scale for the Assessment of Negative Symptoms(SANS)and the Positive and Negative Syndrome Scale(PANSS).RESULTS There were no significant differences in PRM performance metrics,SANS total score,SANS subscores,PANSS total score,and PANSS subscores between active and sham rTMS groups at the end of the 4-wk treatment period,but PRM performance metrics(percent correct and number correct)and changes in these metrics from baseline were significantly greater in the active rTMS group at week 8 compared to the sham group(all P<0.05).Active rTMS treatment also significantly reduced SANS score at week 8 compared to sham treatment.Moreover,the improvement in visual memory was correlated with the reduction in negative symptoms at week 8.In contrast,there were no between-group differences in PANSS total score and subscale scores at either week 4 or week 8(all P>0.05).CONCLUSION High-frequency transcranial magnetic stimulation improves visual memory and reduces negative symptoms in schizophrenia,but these effects are delayed,potentially due to the requirement for extensive neuroplastic changes within DLPFC networks.
基金several colleague therapists of the Rehabilitation Medicine Department of the Affiliated Hospital of Qingdao University of China for their support and selfless help
文摘Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex(M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.
基金supported by the National Natural Science Foundation of China (U21A20361 and 82130039 to Y.W.Z.)Fundamental Research Funds for the Central Universities (20720220133 to Y.W.Z.)+2 种基金Natural Science Foundation of Fujian Province (2021J02057 to Q.L.M.)Science and Technology Plan Projects of Fujian Province (2020Y2015 to Z.X.W.)2020 Joint Support of Key Projects on Health Care (3502Z20209005 to Z.X.W.)。
文摘Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.
