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high-frequency stimulation of anterior nucleus thalamus improves impaired cognitive function induced by intra-hippocampal injection of Aβ1-40 in rats

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Chinese Medical Journal 2014年第1期127卷 125-129页

作者： Chen Ning Dong Shuai Yan Tingshuang Yan Na Ma Yu Yu Chunjiang Department of Neurosurgery Beijing Sanbo Brain Hospital CapitalMedical University Beijing 100093 China Department of Neurology Sixth People's Hospital of Jinan Jinan Shandong 250200 China Critical Care Medicine Sixth People's Hospital of Jinan Jinan Shandong 250200 China School of Public Health and Family Medicine. Capital Medical University Beijing 100069 China Yuquan Hospital Tsinghua University Beijing 100049 China

Background The advent of brain stimulation techniques to treat movement disorders and psychiatric diseases has shown potential to decode the neural mechanism that underlies the cognitive process by modulating the interrupted circuit.Here,the present investigation aimed at evaluating the influence of deep brain stimulation of the anterior nucleus thalamus （ANT-DBS） on memory.Methods Thirty-two rats were randomized into phosphate buffer saline （PBS） group （n=8,rats received PBS injections without implantation of electrodes into the ANT）,Alzheimer＇s dementia （AD） group （n=8,rats received Aβ1-40 injections without implantation of electrodes into the ANT）,ANT sham stimulation group （n=8,rats received Aβ1-40 injections with implantation of electrodes into the ANT but without stimulation） and ANT stimulation group （n=8,rats received Aβ1-40 injections with implantation of electrodes into the ANT and stimulation）.A Morris maze test was used for determining the effect of electrical stimulation on cognitive function in rats.The data were assessed statistically with one-way analysis of variance （ANOVA） followed by Tukey＇s tests for multiple post hoc comparisons.Results The data showed that in the training test,PBS group and AD group managed to learn the hidden-platform faster and faster while AD group needed a significantly longer time to reach the platform than PBS group （P ＜0.05）.Meanwhile,ANT stimulation group demonstrated a significantly shorter time to reach the platform （P ＜0.05） compared to the AD group,while there was no significant difference between the ANT sham stimulation group and the AD group （P ＞0.05）.On the probe test,the AD group spent less time （（10.15±2.34） seconds） in the target quadrant than the PBS group （（28.20±2.75） seconds）（P ＜0.05）.And the times of platform-traversing of the AD group （3.35±1.12） significantly decreased compared with the PBS group （8.69±2.87）（P ＜0.05）.However,the times of platform-traversing and the time spent in the target quadrant of the ANT stimulation group significantly increa

关键词： high-frequency stimulation anterior nucleus thalamus Alzheimer ＇s dementia Aβ1-40

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Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer's disease

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动物学研究(英文) 2023年第5期44卷 867-881页

作者： Ting Wang Yun-Qiang Zhou Yong Wang Liang Zhang Xiang Zhu Xiu-Yan Wang Jing-Hui Wang Lin-Kun Han Jian Meng Xian Zhang Hong Luo Qi-Lin Ma Zhan-Xiang Wang Yun-Wu Zhang Xiamen Key Laboratory of Brain Center The First Affiliated Hospital of Xiamen Universityand Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging ResearchInstitute of NeuroscienceSchool of MedicineXiamen UniversityXiamenFujian 361102China Fujian Provincial Clinical Research Center for Brain Diseases The First Affiliated Hospital of Xiamen UniversityXiamenFujian 361003China

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.

关键词： Alzheimer's disease high-frequency stimulation Long-term potentiation PYGM Synaptic plasticity Transcriptome

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Topical lidocaine reverses neuropathic pain induced by high-frequency stimulation of sciatic nerve and enhances GSK-3β activities to inhibit cytokine production in spinal dorsal horn

Topical lidocaine reverses neuropathic pain induced by high-...

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中国神经科学学会第十届全国学术会议

作者： Xiao WEI Li-Jun ZHOU Wen-Shan GUI Wen-Hui ZHENG Yong-Yong LI Xian-Guo LIU Pain Research Center and Department of Physiology Zhongshan Medicine School of Sun Yat-Sen University

Objective Local anesthetics Udocaine is recommended as first-line treatment for localized peripheral neuropathic pain.However,the mechamsm of this effect has been little explored.high-frequency stimulation（HFS） of the sciatic nerve,which triggers long-term potentiation（LTP） of C-fiber-evoked field potentials（a synaptic model of central sensitization）,produces behavioral signs of neuropathic pain in animals and in human.In this study,we aimed to determine if Udocaine prior to HFS reUeve hyperalgesia,and discussed its possible mechanism.Methods In the sham group,the exposed left sciatic nerve was placed on the stimulation electrode without electrical stimulation.While group HFS received 0.98%saline before HFS（100 Hz,40 V,0.5 ms,100 pulses given in 4 trains of 1-s duration at 10-s intervals） of sciatic nerve,group Lido + HFS received 2%Udocaine（20 min before,3 h and 24 h after HFS,0.1mL each time） proximal to the site of HFS.Results Results of pain behaviors test showed that the multiple treatment of Udocaine before and after HFS completely reversed the decrease of ipsilateral paw withdrawal threshold（PWT） and paw withdrawal latency（PWL） following HFS.Importantly,we found HFS of sciatic nerve,without inducing DRG neurons injury（without ATF-3 up-regulation in DRG）,significantly activated astrocytes as well as microglia from day3 after HFS,and the effect was abolished by treatment with Udocaine.Furthermore,HFS could activate NF-κB,followed by an increased expression of TNF-α and IL-1β production in the ipsilateral dorsal horn.Glycogen synthase kinase-3β（GSK-3β） activated in infectious diseases is known to regulate inflammatory response.However,inactivation of GSK-3β occurred after HFS,and Udocaine rescued the activation of GSK-3β and reduced the activation of NF-κB and TNF-α and IL-1β production.The GSK-3β inhibitor SB216763 not only produced hyperalgesia,but also induced NF-κB activation and subsequent TNF-α and IL-1β production,which indicates that GSK-3β acts upstream of NF-κB in HFS-induced neuropathic pain.Likewi

关键词： lidocaine high-frequency stimulation neuropathic pain GSK-3β NF-κB cytokine

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Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction

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Neural Regeneration Research 2016年第10期11卷 1584-1590页

作者： Jiang Li Xiang-min Meng Ru-yi Li Ru Zhang Zheng Zhang Yi-feng Du Shandong Provincial Hospital of Shandong University Jinan Shandong Province China Affiliated Hospital of Qingdao University Qingdao Shandong Province China

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.

关键词： nerve regeneration brain injury repetitive transcranial magnetic stimulation cerebral infarction low-frequency stimulation high-frequency stimulation upper-limb motor function cerebral cortex stroke rehabilitation motor-evoked potential central motor conductiontime primary motor cortex neuroplasticity neural reorganization neural regeneration

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