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Modifying the progression of Parkinson's disease through movement interventions:multimodal quantification of underlying mechanisms

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Neural Regeneration Research 2024年第8期19卷 1651-1652页

作者： Manuel Bange Damian Marc Herz Dumitru Ciolac Gabriel Gonzalez-Escamilla Sergiu Groppa Section of movement disorders and Neurostimulation Department of NeurologyFocus Program Translational Neuroscience(FTN)University Medical Center of the Johannes Gutenberg-University MainzMainzGermany

Introduction:Parkinson’s disease(PD)is the most common neurodegenerative movement disorder.The pathological hallmark is the progressive loss of dopaminergic neurons of the substantia nigra pars compacta,which is accompanied by widespread alterations in the structu re and function of distributed brain networks.Togethe r,these processes cause a variety of motor symptoms such as bradykinesia,rigidity,tremor,gait disorders,or difficulties in fine motor control(Bange et al.,2022).

关键词： alterations movement

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia

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World Journal of Psychiatry 2024年第5期14卷 695-703页

作者： Wen-Peng Hou Xiang-Qin Qin Wei-Wei Hou Yun-Yi Han Qi-Jing Bo Fang Dong Fu-Chun Zhou Xian-Bin Li Chuan-Yue Wang Beijing Key Laboratory of Mental disorders National Clinical Research Center for Mental Disorders&National Center for Mental DisordersBeijing Anding HospitalCapital Medical UniversityBeijing 100088China Advanced Innovation center for Human Brain Protection Capital Medical UniversityBeijing 100069China

BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

关键词： Catechol-O-methyltransferase Val/Met polymorphism Cognitive reserve Crystallized intelligence Negative symptoms Schizophrenia

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

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Neural Regeneration Research 2024年第2期19卷 440-446页

作者： Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen Cell Therapy center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关键词： biomaterial fibrinogen functional recovery induced neural stem cell transplantation microenvironment microglia spinal cord injury thrombin

The roles of RACK1 in the pathogenesis of Alzheimer's disease

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Journal of Biomedical Research 2024年第2期38卷 137-148页

作者： Wenting He Xiuyu Shi Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Child Neurodevelopment and Cognitive DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.

关键词： RACK1 Alzheimer's disease PKC amyloid-β synaptic plasticity neuroinflammation

Postoperativeinte rictalepil eptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site

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World Journal of Pediatric Surgery 2024年第1期7卷 33-41页

作者： Yuxin Wu ZaiYu Zhang Ping Liang Lusheng Li Bin Zou Difei Wang Xinyu Dong Haotian Tang Hanli Qiu Xuan Zhai Department of Neurosurgery Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqingChina

Objective The study aimed to explore the association between the site of interictal epileptic discharges(IEDs)on postoperative electroencephalogram(EEG)and seizure recurrence after antiepileptic drug(AED)withdrawal.The study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus,while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical stimulation.The former has a higher risk of seizure recurrence.Methods We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection surgery.To identify the risk factors for seizure recurrence,we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate analyses.AED tapering was standardized,involving a 25% reduction in the dose of a single type of AED every 2 weeks,independent of the presurgical AED load.Results We attempted AED withdrawal in 116(63.7%)children.Twenty-eight(24.1%)children experienced seizure recurrence during or after AED withdrawal.A greater number of AEDs used at the time of surgery(p=0.005),incomplete resection(p=0.001),and presence of IED on postoperative EEG(p=0.011)are predictors of seizurerecurrence.Thecompletenessof resectionand seizure recurrence after AED withdrawal were related to the presence of IED on the EEG,but not to the concordance of IED with surgical sites.Conclusion For children with abnormal EEG,the decision to discontinue AED should be made more cautiously,regardless of the relative location of the discharge site and the surgical site.

关键词： surgical seizure epileptic

Network analysis of suicide ideation and depression-anxiety symptoms among Chinese adolescents

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General Psychiatry 2024年第2期37卷 216-223页

作者： Shuyin Xu Yumeng Ju Xiyu Wei Wenwen Ou Mohan Ma Guanyi Lv Xiaotian Zhao Yaqi Qin Yunjing Li Liang Li Mei Huang Siqi Yang Yimei Lu Yafei Chen Junwu Liu Jin Liu Bangshan Liu Yan Zhang Department of Psychiatry National Clinical Research Center for Mental Disordersand National Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina Mental Health Institute of Central South University China National Technology Institute on Mental DisordersHunan Technology Institute of PsychiatryHunan Key Laboratory of Psychiatry and Mental HealthHunan Medical Center for Mental HealthChangshaHunanChina

Background The co-occurrence of depression and anxiety among adolescents is typically associated with suicide ideation.Aims The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and anxiety.Methods 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire(PHQ-9)and the Generalized Anxiety Disorder Scale,and 716 adolescents who scored≥5 on both scales were selected as participants.Network analysis was used to identify the network structure of depressive symptoms and anxiety symptoms.Participants were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9.A comparison was made between the depression-anxiety symptom networks of the two groups.Results‘Restlessness’,‘sad mood’and‘trouble relaxing’were the most prominent central symptoms in the depression-anxiety symptom network,and‘restlessness’,‘nervousness’and‘reduced movement’were the bridge symptoms in this network.‘Sad mood’was found to be directly related to‘suicide ideation’with the highest variance.The network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group,with‘restlessness’and‘sad mood’exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation group.Conclusion Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

关键词： symptoms adolescent assessed

Clinical features and treatment outcomes of major depressive disorder with genital symptoms

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Chinese Medical Journal 2024年第5期137卷 622-624页

作者： Xiaohui Wu Yuncheng Zhu Ping Sun Shuo Wang Zhiguo Wu Jia Huang Lan Cao Yun Wang Yousong Su Zhijian Yao Zuowei Wang Fan Wang Yong Wang Daihui Peng Jun Chen Yiru Fang Department of Clinical Research center&Division of Mood disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Mood disorders Shanghai Hongkou Mental Health CenterShanghai 200083China Department of Psychiatry Nanjing Medical University Affiliated Brain HospitalNanjingJiangsu 210029China Department of Psychiatry&Affective disorders center Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China CAS center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China Shanghai Key Laboratory of Psychotic disorders Shanghai 200118China

To the Editor:Major depressive disorder(MDD)is a mood disorder characterized by complex patterns of emotional,cognitive,and behavioral symptomology and deficits in daily functioning.Genital symptoms,including a reduction in libido and menstrual disturbances,have been considered to be a classic symptom of MDD for many decades.Previous evidence has reached a broad consensus that the incidence of genital symptoms is higher in patients with MDD than in the general population.A systematic review and meta-analysis found a bidirectional association between MDD and genital symptoms,with patients with MDD showing a 50–70%increased risk of developing genital symptoms,while individuals with genital symptoms had a 130–210%increased risk of developing MDD.^([1])As previously reported,50–70%of people with MDD experience sexual dysfunction.^([2])To date,few studies have focused on the comparison of clinical features between patients with MDD with and without genital symptoms,and the longitudinal prognosis.

关键词： symptoms Clinical features

Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical Research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids

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Genes & Diseases 2024年第2期11卷 1066-1081页

作者： Junyan Yan Lu Xiao Di Feng Baolin Chen Ting Yang Bei Tong Ruifang Luo Yuting Wang Jie Chen Children Nutrition Research center Children's Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Child Nutrition and HealthMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing 401122China Department of Gastroenterology Children's Hospital of Chongqing Medical UniversityChongqing 401122China

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function.Short-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is deficient.Thus,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing.In the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated.Intriguingly,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period.Further study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression.Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.

关键词： CEACAM1 Colonic epithelial barrier HDAC3 Short-chain fatty acids Vitamin A deficiency