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Parvalbumin neuroplasticity compensates for somatostatin impairment, maintaining cognitive function in Alzheimer’s disease

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Translational Neurodegeneration 2022年第1期11卷 566-587页

作者： Christopher Daniel Morrone aaron yenhsin lai Jossana Bishay Mary Elizabeth Hill JoAnne McLaurin Biological Sciences Sunnybrook Research InstituteTorontoON M4N 3M5Canada Department of Laboratory Medicine and Pathobiology Temerty Faculty of MedicineUniversity of TorontoTorontoON M5S 1A8Canada

Background: Patient-to-patient variability in the degree to which β-amyloid, tau and neurodegeneration impact cognitive decline in Alzheimer’s disease (AD) complicates disease modeling and treatment. However, the underlying mechanisms leading to cognitive resilience are not resolved. We hypothesize that the variability in cognitive function and loss relates to neuronal resilience of the hippocampal GABAergic network. Methods: We compared TgF344-AD and non-transgenic littermate rats at 9, 12, and 15 months of age. Neurons, β-amyloid plaques and tau inclusions were quantified in hippocampus and entorhinal cortex. Somatostatin (SST) and parvalbumin (PVB) interneurons were traced to examine hippocampal neuroplasticity and cognition was tested in the Barnes maze. Results: The 9-month-old TgF344-AD rats exhibited loss of neurons in the entorhinal cortex and hippocampus. Hippocampal neuronal compensation was observed in 12-month TgF344-AD rats, with upregulation of GABAergic interneuronal marker. By 15 months, the TgF344-AD rats had robust loss of excitatory and inhibitory neurons. β-Amyloid and tau pathology accumulated continuously across age. SST interneurons exhibited tau inclusions and atrophy from 9 months, whereas PVB interneurons were resilient until 15 months. The hippocampal PVB circuit underwent neuroplastic reorganization with increased dendritic length and complexity in 9- and 12-month-old TgF344- AD rats, before atrophy at 15 months. Strikingly, 12-month-old TgF344-AD rats were resilient in executive function and cognitive flexibility. Cognitive resilience in TgF344-AD rats occurred as maintenance of function between 9 and 12 months of age despite progressive spatial memory deficits, and was sustained by PVB neuroplasticity. Conclusions: Our results demonstrate the inherent neuronal processes leading to cognitive maintenance, and describe a novel finding of endogenous cognitive resilience in an AD model.

关键词： Alzheimer’s disease TgF344-AD rat GABAergic interneuron Parvalbumin Somatostatin Barnes maze Hippocampus Neuronal compensation Cognitive resilience

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解决“白马论”：庄子之“白马非马”验证

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杭州师范大学学报（社会科学版） 2016年第2期38卷 1-9页

作者： [英]托马斯·明亚伦·赖顾瑶(译) 刘妮(校) 牛津大学凯洛格学院英国牛津复旦大学人文社会科学论丛上海200433 上海交通大学人文学院上海200240

以庄子对"辩"的否定为问题来源,进而通过公孙龙的"白马论"以及墨子的提示来探讨辩论的真实性、可行性与有效性。在此过程中,可对"辩"、"真"、"可"、"悖"等古代概念与方法进行哲学探讨。在此基础上,从庄子对于择代逻辑(alternative logi... 详细信息

以庄子对"辩"的否定为问题来源,进而通过公孙龙的"白马论"以及墨子的提示来探讨辩论的真实性、可行性与有效性。在此过程中,可对"辩"、"真"、"可"、"悖"等古代概念与方法进行哲学探讨。在此基础上,从庄子对于择代逻辑(alternative logics)的构想进行引申,我们可以从现代哲学的角度重新回应庄子为何既否定"辩"又参与"辩"的问题。

关键词：庄子公孙龙白马论

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Who can benefit more from its twelve-week treatment:A prospective cohort study of blonanserin for patients with schizophrenia

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World Journal of Psychiatry 2024年第11期14卷 1735-1745页

作者： Bao-Yan Xu Kun Jin Hai-Shan Wu Xue-Jun Liu Xi-Jin Wang Hong Sang Ke-Qing Li Mei-Juan Sun Hua-Qing Meng Huai-Li Deng Zhi-Yuan Xun Xiao-Dong Yang Lin Zhang Guan-Jun Li Rui-Ling Zhang Duan-Fang Cai Jia-Hong Liu Gui-Jun Zhao Long-Fa Liu Gang Wang Chang-Lie Zhao Bin Guo Sheng-Chun Jin Ling-Yun Huang Fu-De Yang Jian-Min Zheng Gui-lai Zhan Mao-Sheng Fang Xiang-Jun Meng Guang-Ya Zhang Hai-Min Li Xiang-lai Liu Ju-Hong Li Bin Wu Hai-Yun Li Jin-Dong Chen Department of Psychiatry National Clinical Research Center for Mental DisordersNational Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangsha 410011Hunan ProvinceChina Department of Psychiatry Hebei Provincial Mental Health CenterHebei Key Laboratory of Major Mental and Behavioral DisordersThe Sixth Clinical Medical College of Hebei UniversityBaoding 071000Hebei ProvinceChina Department of Psychiatry Brain Hospital of Hunan ProvinceChangsha 410000Hunan ProvinceChina Department of Psychiatry The First Psychiatric Hospital of HarbinHarbin 150000Heilongjiang ProvinceChina Mental Health Center Changchun Sixth HospitalChangchun 130000Jilin ProvinceChina Department of Pharmacy Daqing Third HospitalDaqing 163000Heilongjiang ProvinceChina Department of Physical and Psychological Rehabilitation Guangda Rehabilitation HospitalChongqing 400000China Department of Psychology Shanxi Provincial Mental Health CenterTaiyuan 030000Shanxi ProvinceChina Department of Psychiatry Tianjin Anding HospitalTianjin 300000China Department of Psychiatry Shandong Mental Health CenterJinan 250000Shandong ProvinceChina Department of Psychiatry Fuzhou Shenkang HospitalFuzhou 350000Fujian ProvinceChina Department of Psychiatry Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200000China Department of Psychiatry The Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453000Henan ProvinceChina Department of Psychiatry The Fifth People’s Hospital of ZigongZigong 643000Sichuan ProvinceChina Department of Psychiatry The Affiliated Kangning Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Psychiatry Guangyuan Mental Health CenterGuangyuan 628000Sichuan ProvinceChina Department of Psychiatry Jilin Sixth People’s HospitalJilin 132000Jilin ProvinceChina The National Clinical Research Center for Mental Disorders&Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital

BACKGROUND Blonanserin(BNS)is a well-tolerated and effective drug for treating *** To investigate which types of patients would obtain the most benefit from BNS *** A total of 3306 participants were evaluated in a 12-week,prospective,multicenter,open-label post-marketing surveillance study of *** psychiatric rating scale(BPRS)scores were calculated to evaluate the effectiveness of BNS,and its safety was assessed with the incidence of adverse drug *** regression was used to screen the influencing factors for the reduction of BPRS total score,and logistic regression was used to identify patients with a better response to *** The baseline BPRS total score(48.8±15.03)decreased to 27.7±10.08 at 12 weeks(P<0.001).Extrapyramidal symptoms(14.6%)were found to be the most frequent adverse drug *** acute phase,baseline BPRS total score,current episode duration,number of previous episodes,dose of concomitant antipsychotics,and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment ***,patients in the acute phase with baseline BPRS total score≥45,current episode duration<3 months,and≤3 previous episodes derived greater benefit from 12-week treatment with *** Patients in the acute phase with more severe symptoms,shorter current episode duration,fewer previous episodes,and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.

关键词： Schizophrenia Blonanserin Effectiveness Psychosocial functioning Prospective cohort study

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