Sex influences genetic susceptibility to depression-like behaviours in chronic unpredictable mild stress-exposed Wistar rats
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Date
2024-07-16
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Publisher
Springer Nature
Abstract
Abstract
Depression is one of the most common mood disorders among psychiatric diseases. It affects about 10% of the adult population.
However, its etiopathogenesis remains poorly understood. Exploring the dynamics of stress-susceptibility and resilience
will help in understanding the molecular and biological mechanisms underlying the etiopathogenesis of depression. This study
aimed to determine the differences and/or similarities in factors responsible for susceptibility to depression-like behaviors
in male and female Wistar rats subjected to chronic unpredictable mild stress (CUMS). Sixty Wistar rats (30 male and 30
female) weighing between 120 and 150 g were used for this study. The rats were divided into two sub-groups: control (10) and
test (20) groups. Rats in the test groups were subjected to CUMS. Depression-like behaviors were assessed using light–dark
box, sucrose preference, and tail suspension tests. Rats that showed depression-like behaviors following the behavioral tests
(CUMS-susceptible group) were sacrificed, and their hippocampi were excised. Genomic deoxyribonucleic acid (gDNA) was
purified from the hippocampal samples. Purified gDNA was subjected to whole genome sequencing (WGS). Base-calling
of sequence reads from raw sequencing signal (FAST5) files was carried out, and variants were called from alignment BAM
files. The corresponding VCF files generated from the variant calling experiment were filtered. Genes were identified, their
impacts estimated, and variants annotated. Functional enrichment analysis was then carried out. Approximately 41% of
the male and 49% of the female rats subjected to CUMS showed significant (p < 0.05) depression-like behaviors following
assessment on behavioral tests. WGS of the hippocampal DNA revealed 289,839 single nucleotide polymorphisms variant
types, 7002 insertions, and 34,459 deletions in males, and 1,570,186 single nucleotide polymorphisms variant types, 109,860
insertions, and 597,241 deletions in female Wistar rats. Three genes with high-impact variants were identified in male and 22
in female Wistar rats, respectively. In conclusion, female Wistar rats are more susceptible to depression-like behaviors after
exposure to CUMS than males. They also have more gene variants (especially high-impact variants) than male Wistar rats.
Description
Keywords
Chronic unpredictable mild stress · Gene variants · Single nucleotide polymorphisms · Susceptibility · Whole genome sequencing
Citation
Chronic unpredictable mild stress; Gene variants; Single nucleotide polymorphisms; Susceptibility; Whole genome sequencing