Protective Role of Acetate Against Depressive-Like Behaviour Associated with Letrozole-Induced PCOS Rat Model: Involvement of HDAC2 and DNA Methylation

Wolugbom, John A.; Areloegbe, Stephanie E.; Olaniyi, Kehinde S.

doi:10.1007/s12035-022-03074-0

Cited by 7 publications

(2 citation statements)

References 52 publications

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“…Following exposure to SPS, sex-specific alterations in these microbial metabolites were apparent: while resilient males displayed elevated cecal acetate levels, susceptible females exhibited heightened branched-chain SCFAs. Notably, acetate, the predominant SCFA, assumes a vital role in histone modification through lysine acetylation, thereby conferring protection against stress-induced physiological and behavioral disruptions [ 119 , 120 ]. While our assessment was directed solely on post-SPS acetate levels, the analysis of GBMs revealed that acetate synthesis I pathway of resilient males was higher even before SPS exposure.…”

Section: Discussionmentioning

confidence: 99%

Microbial composition, functionality, and stress resilience or susceptibility: unraveling sex-specific patterns

Tanelian,

Nankova,

Miari

et al. 2024

Biol Sex Differ

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Background Following exposure to traumatic stress, women are twice as likely as men to develop mood disorders. Yet, individual responses to such stress vary, with some people developing stress-induced psychopathologies while others exhibit resilience. The factors influencing sex-related disparities in affective disorders as well as variations in resilience remain unclear; however, emerging evidence suggests differences in the gut microbiota play a role. In this study, using the single prolonged stress (SPS) model of post-traumatic stress disorder, we investigated pre- and post-existing differences in microbial composition, functionality, and metabolites that affect stress susceptibility or resilience in each sex. Methods Male and female Sprague–Dawley rats were randomly assigned to control or SPS groups. Two weeks following SPS, the animals were exposed to a battery of behavioral tests and decapitated a day later. Based on their anxiety index, they were further categorized as SPS-resilient (SPS-R) or SPS-susceptible (SPS-S). On the day of dissection, cecum, and selected brain tissues were isolated. Stool samples were collected before and after SPS, whereas urine samples were taken before and 30 min into the SPS. Results Before SPS exposure, the sympathoadrenal axis exhibited alterations within male subgroups only. Expression of tight junction protein claudin-5 was lower in brain of SPS-S males, but higher in SPS-R females following SPS. Across the study, alpha diversity remained consistently lower in males compared to females. Beta diversity revealed distinct separations between male and female susceptible groups before SPS, with this separation becoming evident in the resilient groups following SPS. At the genus level, Lactobacillus, Lachnospiraceae_Incertae_Sedis, and Barnesiella exhibited sex-specific alterations, displaying opposing abundances in each sex. Additionally, sex-specific changes were observed in microbial predictive functionality and targeted functional modules both before and after SPS. Alterations in the microbial short-chain fatty acids (SCFAs), were also observed, with major and minor SCFAs being lower in SPS-susceptible males whereas branched-chain SCFAs being higher in SPS-susceptible females. Conclusion This study highlights distinct pre- and post-trauma differences in microbial composition, functionality, and metabolites, associated with stress resilience in male and female rats. The findings underscore the importance of developing sex-specific therapeutic strategies to effectively address stress-related disorders. Highlights SPS model induces divergent anxiety and social behavioral responses to traumatic stress in both male and female rodents. SPS-resilient females displayed less anxiety-like behavior and initiated more interactions towards a juvenile rat than SPS-resilient males. Sex-specific pre-existing and SPS-induced differences in the gut microbial composition and predictive functionality were observed in susceptible and resilient rats. SPS-resilient males displayed elevated cecal acetate levels, whereas SPS-susceptible females exhibited heightened branched-chain SCFAs.

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Section: Discussionmentioning

confidence: 99%

Microbial composition, functionality, and stress resilience or susceptibility: unraveling sex-specific patterns

Tanelian,

Nankova,

Miari

et al. 2024

Biol Sex Differ

View full text Add to dashboard Cite

show abstract

“…Although the mRNA levels of HDAC2 were not increased in SPS + NaCl group, we found a positive correlation between HDAC2 mRNA levels and anxiety index; suggesting that the enzymatic activity might be increased, and thus play a role in the development of anxiety symptoms. To date, only few studies have explored the involvement of acetate in histone acetylation ( Huang et al, 2021 ; Soliman and Rosenberger, 2011 ; Soliman et al, 2012 ; Wolugbom et al, 2023 ). Notably, all these studies employed oral gavage as the delivery method for acetate.…”

Section: Discussionmentioning

confidence: 99%

Effect of acetate supplementation on traumatic stress-induced behavioral impairments in male rats

Tanelian,

Nankova,

et al. 2023

Neurobiology of Stress

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Troxerutin dampened hypothalamic neuroinflammation via microglial IL-22/IL-22R1/IRF3 activation in dihydrotestosterone-induced polycystic ovary syndrome rats

Gao,

Tan,

Song

et al. 2024

Phytomedicine

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Protective Role of Acetate Against Depressive-Like Behaviour Associated with Letrozole-Induced PCOS Rat Model: Involvement of HDAC2 and DNA Methylation

Cited by 7 publications

References 52 publications

Microbial composition, functionality, and stress resilience or susceptibility: unraveling sex-specific patterns

Microbial composition, functionality, and stress resilience or susceptibility: unraveling sex-specific patterns

Effect of acetate supplementation on traumatic stress-induced behavioral impairments in male rats

Troxerutin dampened hypothalamic neuroinflammation via microglial IL-22/IL-22R1/IRF3 activation in dihydrotestosterone-induced polycystic ovary syndrome rats

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