Gut microbiota depletion affects nutritional and behavioral responses to activity-based anorexia model in a sex-dependent manner.
In the last decade, the role of the microbiota-gut-brain axis in eating behavior and anxiety-depressive disorders has gained increasing attention. Although a gut microbiota dysbiosis has been reported in anorectic patients, its pathophysiological role remains poorly understood. Thus, we aimed to characterize the potential role of gut microbiota by evaluating the effects of its depletion in the Activity-Based Anorexia (ABA) mouse model both in male and female mice.
Male and female C57Bl/6 mice were submitted (ABA group) or not (CT group) to the ABA protocol, which combines access to a running wheel with a progressive limited food access. Gut microbiota was previously depleted or not by a cocktail of antibiotics (ATB) delivered by oral gavages. We monitored body composition, anxiety-like behavior, leptin and adiponectin plasma levels, hypothalamic and hippocampal neuropeptides mRNA levels, as well as dopamine (DRD) and serotonin (5HT1 and 4) receptors mRNA expression.
In response to the ABA model, the body weight loss was less pronounced in ATB-treated ABA compared to untreated ABA, while food intake remained unaffected by ATB treatment. ATB-treated ABA exhibited increased fat mass and decreased lean mass compared to untreated ABA both in male and female mice, whereas but plasma adipokine concentrations were affected in a sex-dependent manner. Only male ABA mice showed a reduced anticipatory physical activity in response to ATB treatment. Similarly, anxiety-like behavior was mainly affected in ATB-treated ABA male mice compared to ATB-treated ABA female mice, which was associated with male-specific alterations of hypothalamic CRH mRNA and hippocampal DRD and 5-HT1A mRNA levels.
Our study provides evidence that ATB-induced gut microbiota depletion triggers alterations of nutritional and behavioral responses to the activity-based anorexia model in a sex-dependent manner.
Tirelle P
，Breton J
，Kauffmann A
，Bahlouli W
，L'Huillier C
，Salameh E
，Amamou A
，Jarbeau M
，Guérin C
，Goichon A
，do Rego JC
，Déchelotte P
，Ribet D
，Coëffier M
... -
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The effect of dexamethasone on clock gene mRNA levels in bovine neutrophils and lymphocytes.
Circadian rhythms are driven by oscillating expression of a family of transcription factors called clock genes. In rodents, clock genes drive circadian rhythms in white blood cell function, and glucocorticoids are believed to regulate these rhythms. Little is known about circadian rhythms of cattle white blood cells. The objectives of this study were: (1) to quantify mRNA levels of clock genes in neutrophils and lymphocytes over 24h in healthy steers; and (2) to quantify effects of dexamethasone on clock gene mRNA levels in bovine neutrophils and lymphocytes. We hypothesized that bovine neutrophils and lymphocytes would display 24h variations in clock gene mRNA levels and that those patterns would be disrupted by glucocorticoid treatment. Six Holstein steers were injected with 0 or 0.10mg/kg body weight dexamethasone according to a crossover design. Neutrophils and lymphocytes were collected from jugular blood at 0, 4, 8, 12, 16, 20, and 24h relative to treatment administration. Neutrophil and lymphocyte mRNA levels of the clock genes Clock, Bmal1, Per1, Per2, Cry1, Cry2, Rev-erbα, and CK1ɛ were quantified. For neutrophils, an interaction between treatment and time was found for Clock, Cry1, and CK1ɛ. Time affected Clock, Per1, Cry1, Rev-erbα, and CK1ɛ. For all of those genes except Per1, neutrophils from control steers displayed 24h changes of mRNA levels characteristic of circadian regulated cells. The dexamethasone treatment increased neutrophil mRNA levels of Per1, decreased Clock, Cry1, Cry2, and Rev-erbα, and tended to decrease Bmal1. These results suggest that circadian rhythms have the potential to impact bovine neutrophil function, and that glucocorticoid-induced disruption of neutrophil circadian rhythms may contribute to periparturient immunosuppression. For lymphocytes, an interaction between treatment and time was observed for Per1 and tended to occur for Per2 and Cry2. Although time affected Per1 and Rev-erbα, distinct 24h patterns of lymphocyte clock gene mRNA levels were not evident as they were in neutrophils. Treatment increased Per1 and decreased Cry2, but the magnitude of the treatment effect was small. In summary, 24h patterns in clock gene mRNA levels were observed in bovine neutrophils and to some degree in lymphocytes, and these patterns were disrupted by dexamethasone administration. Although further research is needed, individual variation in white blood cell circadian rhythms and glucocorticoid responsiveness may help to explain individual differences in periparturient disease susceptibility.
Nebzydoski SJ
，Pozzo S
，Nemec L
，Rankin MK
，Gressley TF
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