Identification of stress resilience module by weighted gene co-expression network analysis in Fkbp5-deficient mice

Autor:	Yeong Jae Kim, Sihwan Seol, Hyo Jung Kang, Koeul Choi, Joonhong Kwon
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Prefrontal Cortex Gland morphogenesis Biology lcsh:RC346-429 Tacrolimus Binding Proteins Micro Report Transcriptome 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Glucocorticoid receptor Gene expression Animals Gene Regulatory Networks Chronic stress Molecular Biology Gene lcsh:Neurology. Diseases of the nervous system Mice Knockout Resilience WGCNA Brain Resilience Psychological RNAseq Cell biology 030104 developmental biology FKBP5 Gene Expression Regulation Gene co-expression network Stress Psychological 030217 neurology & neurosurgery
Zdroj:	Molecular Brain, Vol 12, Iss 1, Pp 1-4 (2019) Molecular Brain
ISSN:	1756-6606
Popis:	FKBP5encodes the FK506 binding protein 5, a glucocorticoid receptor (GR) binding protein known to play an important role in the physiological stress response. However, results from previous studies examining the association between common variants ofFKBP5and stress have been inconsistent. To investigate whether the loss ofFKBP5affects the stress response, we examined the behavior of mice following the induction of chronic restraint stress between homozygous wild-type andFkbp5knock-out mice. After 21 days of exposure to restraint stress, WT mice showed anhedonia, a core symptom of depression, which could be measured by a sucrose preference test. However,Fkbp5-deficient mice did not exhibit significant depressive-like behavior compared to the WT after exposure to chronic restraint stress. To investigate the molecular mechanism underlying stress resilience, we performed RNA sequencing analysis. The differentially expressed gene (DEG) analysis showed that chronic stress induced changes in various biological processes involved in cell-cell adhesion and inflammatory response. Weighted gene co-expression network analysis identified 60 characteristic modules that correlated with stress or theFKBP5genotype. Among them, M55 showed a gene expression pattern consistent with behavioral changes after stress exposure, and the gene ontology analysis revealed that this was involved in nervous system development, gland morphogenesis, and inflammatory response. These results suggest thatFKBP5may be a crucial factor for the stress response, and that transcriptomic data can provide insight into stress-related pathophysiology.
Databáze:	OpenAIRE
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