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Mycoplasma fermentans activates the hypothalamo-pituitary adrenal axis in the rat
J Weidenfeld1, A Wohlman, R Gallily
1Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Abstract:
Intracerebroventricular administration in rats of heat inactivated Mycoplasma fermentans caused a dose- and time-dependent increase in serum adrenocorticotrophin (ACTH) and corticosterone (CS). In rats with complete deafferentation of the mediobasal hypothalamus, which markedly depleted the median eminence CRF-41, the ACTH and CS responses to M. fermentans were completely inhibited. Pretreatment with dexamethasone abolished the adrenocortical response to M. fermentans. In lipopolysaccharide (LPS) unresponsive C3H/HeJ mice LPS failed to induce the adrenocortical response while administration of M. fermentans elicited a normal CS response. These results suggest that: M. fermentans can activate the hypothalamo-pituitary-adrenal axis via a central mechanism which involves hypothalamic ACTH secretagogue(s), and this effect is sensitive to the negative feedback of glucocorticoids. It is possible that the elevated glucocorticoid levels resulting from mycoplasma infection may be involved in the pathogenesis of mycoplasma-associated diseases.
Insights
Heat-inactivated Mycoplasma fermentans activates the hypothalamo-pituitary-adrenal axis in rats, increasing adrenocorticotrophin (ACTH) and corticosterone (CS). This response involves central mechanisms and is sensitive to glucocorticoid feedback.
Area of Science:
- Neuroendocrinology
- Immunology
- Microbiology
Background:
- Mycoplasma fermentans infections are associated with various diseases.
- The activation of the hypothalamo-pituitary-adrenal (HPA) axis by microbial components is a known phenomenon.
- Understanding the specific pathways involved in Mycoplasma-induced immune responses is crucial.
Purpose of the Study:
- To investigate the effect of Mycoplasma fermentans on the HPA axis in rats.
- To elucidate the central mechanisms underlying the HPA axis activation by M. fermentans.
- To determine the role of glucocorticoid feedback in this response.
Main Methods:
- Intracerebroventricular administration of heat-inactivated Mycoplasma fermentans in rats.
- Assessment of serum adrenocorticotrophin (ACTH) and corticosterone (CS) levels.
- Studies in rats with hypothalamic deafferentation.
- Administration of dexamethasone to assess glucocorticoid feedback.
- Experiments in lipopolysaccharide (LPS) unresponsive mice.
Main Results:
- M. fermentans administration caused a dose- and time-dependent increase in ACTH and CS.
- Hypothalamic deafferentation completely inhibited the ACTH and CS responses to M. fermentans.
- Dexamethasone pretreatment abolished the adrenocortical response.
- M. fermentans elicited a normal corticosterone response in LPS-unresponsive mice.
Conclusions:
- Mycoplasma fermentans activates the HPA axis through a central mechanism involving hypothalamic ACTH secretagogues.
- The activation pathway is sensitive to negative glucocorticoid feedback.
- Elevated glucocorticoid levels during mycoplasma infection may contribute to disease pathogenesis.