Transthyretin Is Commonly Upregulated in the Hippocampus of Two Stress-Induced Depression Mouse Models.
Hidehito Saito-TakatsujiYasuo YoshitomiRyo YamamotoTakafumi FuruyamaYasuhito IshigakiNobuo KatoHideto YonekuraTakayuki IkedaPublished in: International journal of molecular sciences (2023)
Chronic stress can affect gene expression in the hippocampus, which alters neural and cerebrovascular functions, thereby contributing to the development of mental disorders such as depression. Although several differentially expressed genes in the depressed brain have been reported, gene expression changes in the stressed brain remain underexplored. Therefore, this study examines hippocampal gene expression in two mouse models of depression induced by forced swim stress (FSS) and repeated social defeat stress (R-SDS). Transthyretin (Ttr) was commonly upregulated in the hippocampus of both mouse models, as determined by microarray, RT-qPCR, and Western blot analyses. Evaluation of the effects of overexpressed Ttr in the hippocampus using adeno-associated virus-mediated gene transfer revealed that TTR overexpression induced depression-like behavior and upregulation of Lcn2 and several proinflammatory genes (Icam1 and Vcam1) in the hippocampus. Upregulation of these inflammation-related genes was confirmed in the hippocampus obtained from mice vulnerable to R-SDS. These results suggest that chronic stress upregulates Ttr expression in the hippocampus and that Ttr upregulation may be involved in the induction of depression-like behavior.
Keyphrases
- gene expression
- cerebral ischemia
- stress induced
- depressive symptoms
- mouse model
- poor prognosis
- prefrontal cortex
- cognitive impairment
- dna methylation
- sleep quality
- subarachnoid hemorrhage
- cell proliferation
- genome wide
- brain injury
- blood brain barrier
- oxidative stress
- signaling pathway
- resting state
- mental health
- endothelial cells
- genome wide identification
- copy number
- single cell
- high glucose
- functional connectivity
- transcription factor