PXD043883

PXD043883 is an original dataset announced via ProteomeXchange.

Title	Targeting vulnerable microcircuit in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss
Description	Background:Episodic memory loss is a prominent clinical manifestation of Alzheimer's disease(AD), which is closely related to tau pathology and hippocampal impairment. Given the heterogeneity of brain neurons, the precise role of different brain neurons in terms of their sensitivity to tau accumulation and contribution to AD-like social memory loss remains unclear and requires further investigation. Methods: We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic experiments, social behavioral test, hippocampal electrophysiology, immunofluorescent staining and in vivo optical fiber recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine their effects on social memory in mice. Results: By proteomic and phosphoproteomic analyses, we identified the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, not dorsal CA1 (dCA1), but vCA1, especially its excitatory and PV neurons, were fully filled with mislocated and phosphorylated tau. Overexpression of human Tau (hTau) in excitatory and PV neurons respectively mimicked AD-like tau accumulation, significantly inhibited the neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythm and time-window efficiently ameliorated tau-impaired social memory. Significantly, one-month administration of UA efficiently decreased tau accumulation via autophagy in a TFEB (transcription factor EB)-dependent manner and recovered vCA1 microcircuit to ameliorate tau-impaired social memory.Conclusion: This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1, and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for AD treatment in the future.
HostingRepository	iProX
AnnounceDate	2023-07-19
AnnouncementXML	Submission_2024-03-18_20:13:31.808.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ying Yang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-18 21:35:58	ID requested
1	2023-09-21 00:41:34	announced
2	2023-09-21 23:18:43	announced	2023-09-22: Update information
⏵ 3	2024-03-18 20:13:32	announced	2023-09-22: Update information 2024-03-19: Update information.

Lei HY, Pi GL, He T, Xiong R, Lv JR, Liu JL, Wu DQ, Li MZ, Shi K, Li SH, Yu NN, Gao Y, Yu HL, Wei LY, Wang X, Zhou QZ, Zou PL, Zhou JY, Liu YZ, Shen NT, Yang J, Ke D, Wang Q, Liu GP, Yang XF, Wang JZ, Yang Y, Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss. Mil Med Res, 11(1):16(2024) [pubmed]

submitter keyword: Alzheimer's disease, Tau protein, Ventral hippocampus, Social memory, Ursolic acid, TFEB

Ying Yang
contact affiliation	Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology
contact email	yingyang@hust.edu.cn
lab head
Ying Yang
contact affiliation	Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology
contact email	yingyang@hust.edu.cn
dataset submitter

iProX dataset URI