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Pubertal probiotics mitigate lipopolysaccharide-induced programming of the hypothalamic-pituitary-adrenal axis in
Kevin B Smith1, Emma Murray1, James Gardner Gregory1
1NISE Laboratory, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, Ontario K1N 6N5, Canada.
Insights
Puberty stress can alter the stress response system. Probiotics given during puberty may protect male mice from these stress-induced changes by maintaining glucocorticoid receptor expression.
Area of Science:
- Neuroscience
- Microbiology
- Endocrinology
Background:
- Puberty involves significant brain development and is a critical window for stress programming.
- Stress during puberty can lead to lasting changes in the hypothalamic-pituitary-adrenal (HPA) axis and mental health issues.
- The gut microbiome's role in mediating stress programming of the HPA axis is suggested but not fully understood.
Purpose of the Study:
- To investigate how probiotic exposure affects lipopolysaccharide (LPS)-induced programming of the HPA axis.
- To examine the impact of probiotics on glucocorticoid receptor (GR) expression in key brain regions during puberty.
- To explore potential sex differences in the gut microbiome's influence on HPA axis programming.
Main Methods:
- Male and female mice received either probiotics or control skim milk during puberty.
- Mice were treated with either saline or LPS to induce a stress response.
- Glucocorticoid receptor (GR) expression was measured in the paraventricular nucleus (PVN), basolateral amygdala (BLA), piriform cortex (PIR), and medial prefrontal cortex (mPFC) in adulthood after acute restraint stress.
Main Results:
- Pubertal LPS treatment reduced GR expression in the PVN of control-fed males.
- Probiotic treatment during puberty prevented the LPS-induced decrease in PVN GR expression in males.
- The protective effect of probiotics was specific to males and did not extend to other brain regions or females.
Conclusions:
- The gut microbiome influences the neurophysiology and programming of the HPA axis in pubertal males.
- Probiotics may prevent stress-induced reductions in GR expression in specific brain areas (PVN, PIR) in males.
- Further research is needed to elucidate sex differences in gut-brain communication and HPA axis programming during puberty.
Abstract:
Puberty is a period of rapid cortical and neuronal development. Stress exposure during puberty programs the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to future stressors. However, programming can result in an enduring maladaptation of the HPA axis activity and can be associated with long-term anxiety- and depression-like behaviours. Probiotic treatment mitigates the effect of stress on mental health, suggesting that the gut microbiome may mediate the programming of the HPA axis. However, the mechanism underlying this effect remains elusive. Thus, we investigated the effect of probiotic exposure on lipopolysaccharide (LPS)-induced programming of the HPA axis and glucocorticoid receptor (GR) expression in the paraventricular (PVN), basolateral amygdala (BLA), piriform cortex (PIR), and medial prefrontal cortex (mPFC). Male and female mice were exposed to either probiotics or control skim milk and were treated with either saline or LPS during puberty. Prior to euthanasia in adulthood, mice were restrained for 30 min. The results showed that pubertal LPS treatment permanently decreased GR expression in the PVN in milk fed control males. However, pubertal probiotic treatment blocked the LPS-induced decrease in GR expression in males. Given that this effect is limited to males, further research is required to better understand sex differences in the interactions between the gut microbiome and the programming of the HPA axis during puberty. Nevertheless, our findings suggest that the gut microbiome influences the neurophysiology of the HPA axis and mediates its programming in pubertal males. The prevention of GR reduction in the male PVN and PIR using probiotics illustrates the complexity of the gut-brain communication and compels continued investigation.
