Evidence map›Paper›PMID 40237297›Full record

ArticleCNS neuroscience & therapeutics2025

Depletion of HSP60 in Microglia Leads to Synaptic Dysfunction and Depression-Like Behaviors Through Enhanced Synaptic Pruning in Male Mice.

Wenhui Zhu, Jinlong Chang, Liusuyan Tian, Xiuyan Yang, Weifen Li

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Wenhui ZhuDepartment of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single-Cell and Extracellular Vesicles, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jinlong ChangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Dali University, Dali, China.
Liusuyan TianThe Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Xiuyan YangThe Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Weifen LiSchool of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, China.ORCID 0000-0001-9396-8528

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2022A1515110205Basic and Applied Basic Research Foundation of Guangdong Province 2023A1515011957China Postdoctoral Science Foundation 2023M730077National Natural Science Foundation of China 82301717President's Fund of Nanfang Hospital, Southern Medical University 2024B046Shenzhen Nanshan District Major Scientific Research Program of the People's Republic of China NSZD2023016Shenzhen Nanshan District Scientific Research Program of the People's Republic of China NS2023027
6 · The paper itself

Abstract

aimsMicroglia, as resident macrophages in the brain, play an important role in depression. Heat shock protein 60 (HSP60), as a chaperone protein, plays a role in cell stress. However, the role of microglial HSP60 in depression remains unclear.

methodsCX3CR1-CreER was used to generate microglial-specific HSP60 knockout (HSP60 cKO) mice. Behavioral tests, western blotting, Golgi staining, biochemical assays, and proteomics were employed to assess depression-like symptoms, microglial activation, and synaptic changes.

resultsHSP60 cKO male mice exhibited depressive-like behaviors, without anxiety-like behavior, including increased immobility in the forced swimming and tail suspension tests, reduced sucrose preference, and elevated corticosterone (CORT) levels, indicating HPA axis activation. Microglial activation was confirmed by the increased expression levels of CD68 and CD86, the elevated transcription of the cybb gene, and reduced branch complexity. Enhanced phagocytosis of excitatory synapses, reduced dendritic spine density, and decreased glutamate levels were observed, with downregulation of synaptic proteins (AMPAR2, Synapsin-1, PSD95), indicating dysregulated synaptic pruning. Moreover, GO analysis showed 20 significant differentially expressed proteins (DEPs) from proteomics are associated with the presynaptic endosome, which plays a crucial role in maintaining synaptic function. Treatment with PLX3397, a CSF1R inhibitor, alleviated depressive-like behaviors and restored synaptic density in HSP60 cKO male mice.

conclusionsHSP60 deletion in microglia leads to overactivation of microglia, impaired synaptic function, and depression-like behaviors, highlighting the importance of microglial homeostasis in mood regulation and the potential therapeutic role of microglial modulation.

Indexed as

Chaperonin 60DepressionMicrogliaNeuronal PlasticitySynapsesAnimalsMaleMiceMice, Inbred C57BLMice, KnockoutMitochondrial ProteinsChaperonin 60Hspd1 protein, mouseMitochondrial ProteinsdepressionHSP60microgliaphagocytosissynapse

Identifiers

PMID40237297
PMCPMC12001071

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.