Assessment of Adrenotoxicity Induced on Prenatal Exposure to Bacterial Endotoxin Lipopolysaccharide: an Age-Related Study in Mice

Abstract

Preclinical and clinical studies have reported that psychiatric illness stems from exposure to infection during early life. Infection-induced increase in proinflammatory cytokines and further activation of the hypothalamic–pituitary–adrenal (HPA) axis are considered the main factors behind mental illness. The present study elucidated the impairment of HPA axis of female mice prenatally challenged with bacterial endotoxin lipopolysaccharide (LPS). The impairment was evaluated through detailed investigation of adrenal histopathology, the end target endocrine gland of HPA axis, plasma levels of pituitary adrenocorticotropic hormone (ACTH) and corticosterone (CORT). In view of the role of pituitary hormone prolactin (PRL) in modulation of HPA axis under infection, plasma level of PRL was also assessed. The evaluation was done at three different life stages of adulthood, i.e., postnatal day (PND) 85, PND 120 and PND 200. Distinct histopathological alterations in adrenal were revealed: distorted arrangement of zona fasciculata cells, localized cytoplasmic vacuolization and accumulation of lipid droplets were some of the disruptions of the adrenal cortex. Medulla showed distinct vascular congestion and disruptions of chromaffin cells with pyknotic nuclei. Plasma levels of ACTH and CORT were significantly elevated, but PRL was lowered. Bacterial endotoxin LPS might have interfered at different levels of hypothalamus, pituitary and directly on adrenal as well acting through its receptors to induce adrenotoxicity. An age-dependent HPA axis impairment was noted; the persistence of the adrenal toxicity was to a greater degree at PND 200 than PND 120 and PND 85 suggesting the reason for the susceptibility of old age to mental illness.