GRK5 Deficiency in the Hippocampus Leads to Cognitive Impairment via Abnormal Microglial Alterations

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	GRK5 Deficiency in the Hippocampus Leads to Cognitive Impairment via Abnormal Microglial Alterations
	Shen, HT; Zhang, TZ; Ji, Y; Zhang, Y; Wang, YX; Jiang, YL; Chen, XJ; Liang, QH; Wu, KF; Li, YF; Lu, XY; Cui, LL; Zhao, B; Wang, Y
	2023
发表期刊	MOLECULAR NEUROBIOLOGY
ISSN	0893-7648
卷号	60 期号:3 页码:1547-1562
摘要	GRK5 is a member of the G protein-coupled receptor (GPCR) kinase family and is closely associated with heart and nervous system disease. It has been reported that GRK5 is closely related to cerebral nerve function and neurodegenerative diseases. However, the biological function of GRK5 in the brain and the influence of GRK5 deficiency on cognitive dysfunction associated with neurodegenerative diseases are unknown. Here, we reported that mice with reduced GRK5 in the hippocampus exhibit cognitive impairment and some Alzheimer's disease (AD)-related molecular pathologies, such as significant neuronal damage and loss, enhanced tau protein phosphorylation, and increased levels of A beta peptides in the hippocampus. Mechanistically, we observed that GRK5 is located in microglia and plays an essential role in maintaining the morphology and function of microglia. GRK5 deficiency elicits microglial morphology changes and proinflammatory-associated gene increases. In addition, transcriptional analysis of hippocampal tissues revealed striking changes in neuroactive ligand-receptor interactions and TNF signaling in GRK5-deficient mice. In conclusion, our results further confirm the vital role of GRK5 in maintaining normal cognitive function in mice. This finding suggests a possible mechanism by which GRK5 maintains microglial homeostasis, and its loss may induce microglial function deficits and cause some AD-related molecular pathogenesis.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14097
专题	其他
推荐引用方式 GB/T 7714	Shen, HT,Zhang, TZ,Ji, Y,et al. GRK5 Deficiency in the Hippocampus Leads to Cognitive Impairment via Abnormal Microglial Alterations[J]. MOLECULAR NEUROBIOLOGY,2023,60(3):1547-1562.
APA	Shen, HT.,Zhang, TZ.,Ji, Y.,Zhang, Y.,Wang, YX.,...&Wang, Y.(2023).GRK5 Deficiency in the Hippocampus Leads to Cognitive Impairment via Abnormal Microglial Alterations.MOLECULAR NEUROBIOLOGY,60(3),1547-1562.
MLA	Shen, HT,et al."GRK5 Deficiency in the Hippocampus Leads to Cognitive Impairment via Abnormal Microglial Alterations".MOLECULAR NEUROBIOLOGY 60.3(2023):1547-1562.

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2024061315.pdf（12563KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文