Sex influences genetic susceptibility to depression-like behaviours in chronic unpredictable mild stress-exposed Wistar rats

dc.contributor.authorJimoh‑Abdulghaffaar Hidaayah Oluwamayowa
dc.contributor.authorJoel Ireoluwa Yinka
dc.contributor.authorJimoh Olanrewaju Saheed
dc.contributor.authorGaniyu Kaosara Oyinola
dc.contributor.authorAlatiba Temidayo Micheal
dc.contributor.authorOgunyomi Victory Oluwaseyi
dc.contributor.authorAdebayo Muhammed Salaudeen
dc.contributor.authorAwoliyi Victoria Tolulope
dc.contributor.authorAgaka Adamah Olamide
dc.contributor.authorOyedeji Aminat Bolatito
dc.contributor.authorKolade Ifeoluwa A.
dc.contributor.authorOjulari Lekan Sheriff
dc.date.accessioned2025-05-07T10:50:31Z
dc.date.available2025-05-07T10:50:31Z
dc.date.issued2024-07-16
dc.description.abstractAbstract 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.
dc.identifier.citationChronic unpredictable mild stress; Gene variants; Single nucleotide polymorphisms; Susceptibility; Whole genome sequencing
dc.identifier.urihttps://doi.org/10.1007/s12035-024-04348-5
dc.identifier.urihttps://uilspace.unilorin.edu.ng/handle/123456789/16300
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.ispartofseries62; 1591-1604
dc.subjectChronic unpredictable mild stress · Gene variants · Single nucleotide polymorphisms · Susceptibility · Whole genome sequencing
dc.titleSex influences genetic susceptibility to depression-like behaviours in chronic unpredictable mild stress-exposed Wistar rats
dc.typeArticle

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