Prefrontal parvalbumin interneurons deficits mediate early emotional dysfunction in Alzheimer's disease

被引：18
|
作者：
Shu, Shu [1 ,2 ,3 ,4 ,5 ,6 ]
Xu, Si-Yi [1 ,2 ,7 ]
Ye, Lei [1 ,2 ]
LiU, Yi [1 ,2 ,3 ,4 ,5 ,6 ]
Cao, Xiang [1 ,2 ,3 ,4 ,5 ,6 ]
Jia, Jun-Qiu [1 ,2 ]
Bian, Hui-Jie [1 ,2 ,8 ]
Liu, Ying [1 ,2 ]
Zhu, Xiao-Lei [1 ,2 ,3 ,4 ,5 ,6 ]
Xu, Yun [1 ,2 ,3 ,4 ,5 ,6 ]
机构：
[1] Nanjing Univ, Med Sch, Dept Neurol, Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China
[2] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210008, Jiangsu, Peoples R China
[3] Nanjing Univ, Inst Brain Sci, Nanjing 210093, Jiangsu, Peoples R China
[4] Med Sch Nanjing Univ, Jiangsu Key Lab Mol Med, Nanjing 210008, Jiangsu, Peoples R China
[5] Jiangsu Prov Stroke Ctr Diag & Therapy, Nanjing 210008, Jiangsu, Peoples R China
[6] Nanjing Neuropsychiat Clin Med Ctr, Nanjing 210008, Jiangsu, Peoples R China
[7] Jiangsu Univ, Nanjing Drum Tower Hosp Clin Coll, Zhenjiang 212013, Jiangsu, Peoples R China
[8] Nanjing Univ Chinese Med, Nanjing Drum Tower Hosp Clin Coll, Nanjing 210023, Jiangsu, Peoples R China
来源：
NEUROPSYCHOPHARMACOLOGY | 2023年 / 48卷 / 02期
基金：
中国国家自然科学基金; 中国博士后科学基金;
关键词：
CIRCUIT DYSFUNCTION; INHIBITION; SYNAPSES; CORTEX; MOUSE; MEMORY;
D O I：
10.1038/s41386-022-01435-w
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Alzheimer's disease (AD) is the most common neurodegenerative disease and has an insidious onset. Exploring the characteristics and mechanism of the early symptoms of AD plays a critical role in the early diagnosis and intervention of AD. Here we found that depressive-like behavior and short-term spatial memory dysfunction appeared in APPswe/PS1dE9 mice (AD mice) as early as 9-11 weeks of age. Electrophysiological analysis revealed excitatory/inhibitory (E/I) imbalance in the prefrontal cortex (PFC). This E/I imbalance was induced by significant reduction in the number and activity of parvalbumin interneurons (PV+ INs) in this region. Furthermore, optogenetic and chemogenetic activation of residual PV+ INs effectively ameliorated depressive-like behavior and rescued short-term spatial memory in AD mice. These results suggest the PFC is selectively vulnerable in the early stage of AD and prefrontal PV+ INs deficits play a key role in the occurrence and development of early symptoms of AD.
引用
收藏
页码：391 / 401
页数：11
相关论文
共 50 条
  • [31] Early Deficits in Cortical Control of Swallowing in Alzheimer's Disease
    Humbert, Ianessa A.
    McLaren, Donald G.
    Kosmatka, Kris
    Fitzgerald, Michele
    Johnson, Sterling
    Porcaro, Eva
    Kays, Stephanie
    Umoh, Eno-Obong
    Robbins, JoAnne
    JOURNAL OF ALZHEIMERS DISEASE, 2010, 19 (04) : 1185 - 1197
  • [32] Pharmacogenetic activation of parvalbumin interneurons in the prefrontal cortex rescues cognitive deficits induced by adolescent MK801 administration
    Linda A. Chamberlin
    Sha-Sha Yang
    Erin P. McEachern
    Joshua T. M. Lucas
    Owen W. McLeod II
    Claire A. Rolland
    Nancy R. Mack
    Brielle R. Ferguson
    Wen-Jun Gao
    Neuropsychopharmacology, 2023, 48 : 1267 - 1276
  • [33] GAD67 Deficiency in Parvalbumin Interneurons Produces Deficits in Inhibitory Transmission and Network Disinhibition in Mouse Prefrontal Cortex
    Lazarus, Matthew S.
    Krishnan, Keerthi
    Huang, Z. Josh
    CEREBRAL CORTEX, 2015, 25 (05) : 1290 - 1296
  • [34] Pharmacogenetic activation of parvalbumin interneurons in the prefrontal cortex rescues cognitive deficits induced by adolescent MK801 administration
    Chamberlin, Linda A.
    Yang, Sha-Sha
    McEachern, Erin P.
    Lucas, Joshua T. M.
    McLeod Ii, Owen W.
    Rolland, Claire A.
    Mack, Nancy R.
    Ferguson, Brielle R.
    Gao, Wen-Jun
    NEUROPSYCHOPHARMACOLOGY, 2023, 48 (09) : 1267 - 1276
  • [35] Ribosome dysfunction is an early event in Alzheimer's disease
    Ding, QX
    Markesbery, WR
    Chen, QH
    Li, F
    Keller, JN
    JOURNAL OF NEUROSCIENCE, 2005, 25 (40): : 9171 - 9175
  • [36] Optogenetic Inhibition of Parvalbumin-Positive Interneurons in Mice as a Model for Neural Network Dysfunction in the Medial Prefrontal Cortex
    Toader, Oana
    Schuelert, Niklas
    Nissen, Wiebke
    von Heimendahl, Moritz
    Rosenbrock, Holger
    BIOLOGICAL PSYCHIATRY, 2018, 83 (09) : S313 - S313
  • [37] Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer's pathology
    Kumar, Prateek
    Goettemoeller, Annie M.
    Espinosa-Garcia, Claudia
    Tobin, Brendan R.
    Tfaily, Ali
    Nelson, Ruth S.
    Natu, Aditya
    Dammer, Eric B.
    Santiago, Juliet V.
    Malepati, Sneha
    Cheng, Lihong
    Xiao, Hailian
    Duong, Duc D.
    Seyfried, Nicholas T.
    Wood, Levi B.
    Rowan, Matthew J. M.
    Rangaraju, Srikant
    NATURE COMMUNICATIONS, 2024, 15 (01)
  • [38] Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology
    Prateek Kumar
    Annie M. Goettemoeller
    Claudia Espinosa-Garcia
    Brendan R. Tobin
    Ali Tfaily
    Ruth S. Nelson
    Aditya Natu
    Eric B. Dammer
    Juliet V. Santiago
    Sneha Malepati
    Lihong Cheng
    Hailian Xiao
    Duc D. Duong
    Nicholas T. Seyfried
    Levi B. Wood
    Matthew J. M. Rowan
    Srikant Rangaraju
    Nature Communications, 15
  • [39] Impaired Awareness of Deficits in Alzheimer's Disease: The Role of Everyday Executive Dysfunction
    Amanzio, Martina
    Vase, Lene
    Leotta, Daniela
    Miceli, Renato
    Palermo, Sara
    Geminiani, Giuliano
    JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY, 2013, 19 (01) : 63 - 72
  • [40] Corticothalamic network dysfunction and behavioral deficits in a mouse model of Alzheimer's disease
    Hazra, Anupam
    Corbett, Brian F.
    You, Jason C.
    Aschmies, Suzan
    Zhao, Lijuan
    Li, Ke
    Lepore, Angelo C.
    Marsh, Eric D.
    Chin, Jeannie
    NEUROBIOLOGY OF AGING, 2016, 44 : 96 - 107
12345