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Altered functional connectivity networks of hippocampal subregions in remitted late-onset depression:a longitudinal resting-state study

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Neuroscience Bulletin 2015年第1期31卷 13-21页

作者： Zan Wang Yonggui Yuan Feng Bai Hao Shu Jiayong You Lingjiang Li Zhijun Zhang neurology department Affiliated ZhongDa HospitalNeuropsychiatric Institute and Medical School of Southeast University department of Psychosomatics and Psychiatry Affiliated ZhongDa HospitalMedical School of Southeast University department of Psychiatry Nanjing Brain Hospital Affiliated to Nanjing Medical University Mental Health Institute Second Xiangya Hospital of Central South University

The regional specifi city of hippocampal abnormalities in late-life depression（LLD） has been demonstrated in previous studies. In this study,we sought to examine the functional connectivity（FC） patterns of hippocampal subregions in remitted late-onset depression（r LOD）,a special subtype of LLD. Fourteen r LOD patients and 18 healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging scans at baseline and at ~21 months of follow-up. Each hippocampus was divided into three parts,the cornu ammonis（CA）,the dentate gyrus,and the subicular complex,and then six seed-based hippocampal subregional networks were *** changes of the six networks over time were directly compared between the rL OD and control groups. From baseline to follow-up,the r LOD group showed a greater decline in connectivity of the left CA to the bilateral posterior cingulate cortex/precuneus（PCC/PCUN）,but showed increased connectivity of the right hippocampal subregional networks with the frontal cortex（bilateral medial prefrontal cortex/anterior cingulate cortex and supplementary motor area）. Further correlative analyses revealed thatthe longitudinal changes in FC between the left CA and PCC/PCUN were positively correlated with longitudinal changes in the Symbol Digit Modalities Test（r = 0.624,P = 0.017） and the Digit Span Test（r = 0.545,P = 0.044） scores in the r LOD group. These results may provide insights into the neurobiological mechanism underlying the cognitive dysfunction in r LOD patients.

关键词： remitted late-onset depression hippocampal subregional network functional connectivity functional magnetic resonance imaging cognitive dysfunction

Serotonin:A Bridge for Infant-mother Bonding

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Neuroscience Bulletin 2023年第11期39卷 1741-1744页

作者： Jingkai Fan Han Xu department of neurobiology and department of neurology of the second affiliated hospital Zhejiang University School of MedicineHangzhou310058China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-machine IntelligenceZhejiang UniversityHangzhou311121China NHC and CAMS Key Laboratory of Medical neurobiology Zhejiang UniversityHangzhou310058China Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou310015China

Maternal affiliation behavior by infants is one of the most important social behaviors of *** to its mother is optimal to ensure nutrition and protection,and therefore essential for an infant's *** importantly,maternal affiliation benefits animals'mental and physical health in adulthood[1].Despite the importance of maternal affiliation,its underlying molecular and circuit mechanisms are only partially *** vocalizations(USVs)emitted by mice and rats have been extensively studied in infant-mother behaviors since USVs reflected pups'emotional states and the eagerness to communicate with their mothers[2].

关键词： mother spite emotional

Perivascular spaces relate to the course and cognition of Huntington’s disease

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Translational Neurodegeneration 2023年第1期12卷 546-549页

作者： Xiao-Yan Li Juan-Juan Xie Jin-Hong Wang Yu-Feng Bao Yi Dong Bin Gao Ting Shen Pei-Yu Huang Hao-Chao Ying Han Xu Anna Wang Roe Hsin-Yi Lai Zhi-Ying Wu department of Medical Genetics and Center for Rare Diseases Department of Neurology in Second Affiliated HospitalKey Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouChina Interdisciplinary Institute of Neuroscience and Technology College of Biomedical Engineering and Instrument ScienceKey Laboratory for Biomedical Engineering of Ministry of EducationZhejiang UniversityHangzhouChina College of Computer science and Technology Zhejiang UniversityHangzhouChina department of Radiology Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina school of Public Health Zhejiang UniversityHangzhouChina MOE Frontier science Center for brain Research and brain-Machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouChina CAS Center for Excellence in brain science and Intelligence Technology ShanghaiChina

Huntington’s disease(HD)is an autosomal dominant neurodegenerative disease that is caused by a cytosine-adenine-guanine(CAG)expansion in the first exon of the huntingtin(HTT)gene,which codes for the hun-tingtin *** typically manifests with a triad of symptoms,including motor disorders,cognitive impair-ment and psychiatric disturbances[1].HD primar-ily affects the basal ganglia(BG),especially the caudate and putamen,after which it extends to more widespread gray and white matter[2].Perivascular spaces(PVSs)are fluid-filled extensions of the subarachnoid spaces that enclose cerebral blood vessels and extend from the cer-ebral cortex through the brain *** physi-ological role of PVSs is the drainage of brain interstitial fluid into perivascular pathways for the elimination of waste products through the glymphatic drainage *** increasing number of studies have demonstrated that enlarged PVSs indicate glymphatic dysfunction and are associated with many neurological diseases,such as Alzheimer’s disease,Parkinson’s disease and small vessel disease[3].With the advantage of strong field strengths,7.0 T images show superior resolution and signal-to-noise ratios than 3.0 T,which facilitate the visualization of *** automated segmentation methods could accurately identify PVS in a short time with no inter-rater *** the current study,we used U-shaped networks(U-net),a class of deep learning methods,to explore the PVS distribution in HD and *** date,PVS distribution in HD is still *** two studies have investigated PVSs in HD,and both dem-onstrated increased visible PVS burden in manifest HD compared to controls[4,5].However,whether PVS bur-den increases in premanifest HD(pre-HD)individuals remains unknown,and the relationship of PVS with cog-nitive decline has never been studied.

关键词： Huntington filled elimination

Pathological Networks Involving Dysmorphic Neurons in Type ⅡFocal Cortical Dysplasia

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Neuroscience Bulletin 2022年第9期38卷 1007-1024页

作者： Yijie Shao Qianqian Ge Jiachao Yang Mi Wang Yu Zhou Jin-Xin Guo Mengyue Zhu Jiachen Shi Yiqi Hu Li Shen Zhong Chen Xiao-Ming Li Jun-Ming Zhu Jianmin Zhang Shumin Duan Jiadong Chen Center for Neuroscience and department of Neurosurgery of the second affiliated hospital NHC and CAMS Key Laboratory of Medical NeurobiologyMOE Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang University School of MedicineHangzhou310058China department of Neurosurgery of the second affiliated hospital Zhejiang University School of MedicineHangzhou310009China The MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology Life Sciences InstituteZhejiang UniversityHangzhou310058China department of Orthopedic Surgery School of Medicinethe Second Affiliated HospitalZhejiang UniversityHangzhou310009China Hangzhou Innovation Center Zhejiang UniversityHangzhou310058China Institute of Pharmacology&Toxicology NHC and CAMS Key Laboratory of Medical NeurobiologyCollege of Pharmaceutical SciencesSchool of Basic Medical SciencesZhejiang UniversityHangzhou310058China Key Laboratory of Neuropharmacology and Translational medicine of Zhejiang Province College of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou310058China Center for Neuroscience and department of neurology of the second affiliated hospital Zhejiang University School of MedicineHangzhou310058China NHC and CAMS Key Laboratory of Medical neurobiology Center for Brain Science and Brain-Inspired IntelligenceJoint Institute for Genetics and Genome Medicine betweenGuangdong Hong Kong Macao Greater Bay AreaZhejiang University and the University of TorontoZhejiang University School of MedicineHangzhou310058China

Focal cortical dysplasia(FCD)is one of the most common causes of drug-resistant *** neurons are the major histopathological feature of typeⅡFCD,but their role in seizure genesis in FCD is *** we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy *** analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in typeⅡFCD,including an enlarged soma,aberrant dendritic arbors,increased current injection for rheobase action potential firing,and reduced action potential firing ***,the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na^(+)-K^(+)-Cl^(−)*** addition,we found a depolarizing shift of the GABA reversal potential in the CamKⅡ-cre::PTENflox/flox mouse model of drug-resistant epilepsy,suggesting that enhanced GABAergic inputs might depolarize dysmorphic ***,imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in typeⅡFCD.

关键词： Focal cortical dysplasia Dysmorphic neuron Whole-cell patch-clamp recording Morphological reconstruction Excitation-inhibition balance

Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson's disease

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Neuroscience Bulletin 2015年第2期31卷 245-256页

作者： Na Zhao Jianqiu Xiao Zhiyong Zheng Guoqiang Fei Feng Zhang Lirong Jin Chunjiu Zhong department of neurology Zhongshan Hospital and Shanghai Medical College State Key Laboratory of Medical neurobiology Institute of brain science Fudan University school of Life sciences Fudan University Xinxiang College of medicine

Our previous studies have demonstrated that ceruloplasmin （CP） dysmetabolism is correlated with Parkinson＇s disease （PD）. However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene （both promoter and coding regions） were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms （SNPs）. High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/ iron metabolism. The frequencies of eight SNPs （one intronic SNP and seven promoter SNPs of the CP gene） and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

关键词： Parkinson's disease ceruloplasmin single-nucleotide polymorphism haplotype copy-number variation

Exosomes in Parkinson's Disease

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Neuroscience Bulletin 2017年第3期33卷 331-338页

作者： Xiaoqing Wu Tingting Zheng Baorong Zhang department of neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of neurology Xinchang People's HospitalXinchang 312500China

Exosomes, nano-sized extracellular vesicles secreted by most cell types, are found in all kinds of biological fluids and tissues, including the central nervous system（CNS）. The proposed functions of these vesicles include roles in cell–cell signaling, removal of cellular debris, and transfer of pathogens between cells. Many studies have revealed that exosomes derived from the CNS occur in the cerebrospinal fluid and peripheral body fluids,and their contents are altered during disease, making them an appealing target for biomarker development in Parkinson＇s disease（PD）. Exosomes have been shown to spread toxic a-synuclein（asyn） between cells and induce apoptosis, which suggests a key mechanism underlying the spread of asyn aggregates in the brain and the acceleration of pathology in PD. However, potential neuroprotective roles of exosomes in PD have also been reported. On the treatment side, as drug delivery vehicles, exosomes have been used to deliver small interfering RNAs and catalase to the brain, and have shown clear therapeutic effects in a mouse model of PD. These features of exosomes in PD make them extremely interesting from the point of view of developing novel diagnostic and therapeutic approaches.

关键词： Exosomes Parkinson’s disease Biomarker Pathology Therapy

Induction of Anxiety-Like Phenotypes by Knockdown of Cannabinoid Type-1 Receptors in the Amygdala of Marmosets

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Neuroscience Bulletin 2023年第11期39卷 1669-1682页

作者： Lin Zhu Di Zheng Rui Li Chen-Jie Shen Ruolan Cai Chenfei Lyu Binliang Tang Hao Sun Xiaohui Wang Yu Ding Bin Xu Guoqiang Jia Xinjian Li Lixia Gao Xiao-Ming Li department of neurobiology and department of neurology of second affiliated hospital Zhejiang University School of MedicineHangzhou310058China NHC and CAMS Key Laboratory of Medical neurobiology MOE Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brian MedicineZhejiang UniversityHangzhou310058China Interdisciplinary Institute of Neuroscience and Technology Zhejiang University School of MedicineHangzhou310029China Center for brain science and brain-Inspired Intelligence Research Units for Emotion and Emotion DisordersChinese Academy of Medical SciencesChina/Guangdong-Hong Kong-Macao Greater Bay AreaJoint Institute for Genetics and Genome Medicine Between Zhejiang University and University of TorontoHangzhou310058China Rehabilitation medicine Center Rehabilitation&Sports Medicine Research Institute of Zhejiang ProvinceDepartment of Rehabilitation MedicineZhejiang Provincial People’s HospitalAffiliated People’s HospitalHangzhou Medical CollegeHangzhou311399China

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and ***,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 ***,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 *** found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social ***,marmosets with CB1R-knockdown had up-regulated plasma cortisol *** 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.

关键词： Cannabinoid type-1 receptor Amygdala Marmoset Anxiety CRISPR/Cas9

brain-wide Mapping of Mono-synaptic Afferents to Different Cell Types in the Laterodorsal Tegmentum

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Neuroscience Bulletin 2019年第5期35卷 781-790页

作者： Xiaomeng Wang Hongbin Yang Libiao Pan Sijia Hao Xiaotong Wu Li Zhan Yijun Liu Fan Meng Huifang Lou Ying Shen Shumin Duan Hao Wang department of neurobiology and department of Neurosurgery of The second affiliated hospital Key Laboratory of Medical Neurobiology of the Ministry of Health of ChinaNHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine

The laterodorsal tegmentum(LDT) is a brain structure involved in distinct behaviors including arousal,reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains *** a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex(VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive(PV?) GABAergic cells received preferential projections from local LDT *** regard to the different subtypes of GABAergic cells, aconsiderable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatinpositive cells than to PV?cells. Diverse inputs to the LDT on a system-wide level were revealed.

关键词： Laterodorsal tegmentum Rabies virus retrograde tracing Limbic lobe Mice

Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions

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Frontiers of medicine 2021年第6期15卷 877-886页

作者： Yulan Chen Dianfu Chen Shaoyun Zhao Gonglu Liu Hongfu Li Zhi-Ying Wu department of neurology and Research Center of neurology in second affiliated hospital and Key Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhou310009China department of neurology Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai200040China

Proline-rich transmembrane protein 2(PRRT2)is the leading cause of paroxysmal kinesigenic dyskinesia(PKD),benign familial infantile epilepsy(BFIE),and infantile convulsions with choreoathetosis(ICCA).Reduced penetrance of PRRT2 has been observed in previous studies,whereas the exact penetrance has not been evaluated *** objective of this study was to estimate the penetrance of PRRT2 and determine its influencing *** screened 222 PKD index patients and their available relatives,identified 39 families with pathogenic or likely pathogenic(P/LP)PRRT2 variants via Sanger sequencing,and obtained 184 PKD/BFIE/ICCA families with P/LP PRRT2 variants from the *** was estimated as the proportion of affected variant ***2 penetrance estimate was 77.6%(95%confidence interval(CI)74.5%–80.7%)in relatives and 74.5%(95%CI 70.2%–78.8%)in obligate *** addition,we first observed that penetrance was higher in truncated than in non-truncated variants(75.8%versus 50.0%,P=0.01),higher in Asian than in Caucasian carriers(81.5%versus 68.5%,P=0.004),and exhibited no difference in gender or parental *** results are meaningful for genetic counseling,implying that approximately three-quarters of PRRT2 variant carriers will develop PRRT2-related disorders,with patients from Asia or carrying truncated variants at a higher risk.

关键词： penetrance PRRT2 paroxysmal kinesigenic dyskinesia infantile convulsions