Spatial transcriptome changes in striatum brain region of model mice subjected to chronic social defeat stress
10.3867/j.issn.1000-3002.2024.08.002
- VernacularTitle:慢性社交挫败应激模型小鼠纹状体脑区空间转录组的变化
- Author:
Wenxin YUN
1
,
2
;
Zhen HE
;
Fanxing XU
;
Fei LI
;
Ning WU
Author Information
1. 沈阳药科大学无涯创新学院,辽宁 沈阳 110016
2. 军事医学研究院国家安全特需药品全国重点实验室,神经精神药理学北京市重点实验室,北京 100850
- Keywords:
chronic social defeat stress;
depression;
spatial transcriptomics;
striatum
- From:
Chinese Journal of Pharmacology and Toxicology
2024;38(8):575-586
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the transcriptomal charactersistics of the striatum in the chronic social defeat stress(CSDS)model mice by using spatial transcriptome analysis and to address the underlying mechanism of the striatum in regulating depressive states.METHODS The CSDS para-digm was employed to establish a depression-like mouse model.The depressive indicators of behavioral despair,anhedonia,and social disorders were assessed through a battery of tests,including the tail suspension test,forced swim test,sucrose preference test,and social interaction experiments.The control mice and the mice exhibiting CSDS-sensitive depression-like behaviors were selected for spatial tran-scriptome sequencing of the striatal region.This sequencing aimed to identify highly expressed genes,followed by KEGG and GO enrichment analyses using the DAVID database.RESULTS The CSDS mouse model effectively induced behavioral despair,anhedonia and social avoidance(P<0.05,P<0.01).Spatial transcriptome analysis revealed 193 differentially expressed genes in the striatum of normal mice.KEGG and GO analyses indicated that these genes were primarily associated with striatal devel-opment,locomotor behaviors,and drug addiction.They were strongly implicated in signaling pathways such as cyclic adenosine monophosphate,cyclic guanosine monophosphate-protein kinase G,calcium signaling,Ras-related protein 1,and mitogen-activated protein kinase,and synaptic linked to GABAergic and dopaminergic neurons.In contrast,CSDS modeling mice led to the identification of 298 differentially expressed genes in the striatum compared with the normal control mice.These genes were significantly enriched in pathways related to neurodegenerative diseases,including Huntington disease,Alzheimer disease,and Parkinson disease.CONCLUSION Depressive states induced by CSDS are associated with the pathological processes underlying neurodegenerative diseases in the striatum.
