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Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary-adrenal axis: early illness and later responsivity to stress.
J Neurosci. 1995 Jan; 15(1 Pt 1):376-84.JN

Abstract

The long-term consequences of neonatal endotoxin exposure on hypothalamic-pituitary-adrenal axis (HPA) function were assessed in adult female and male Long-Evans rats. At 3 and 5 d of age, pups were administered endotoxin (Salmonella enteritidis, 0.05 mg/kg, i.p.) at a dose that provokes a rapid and sustained physiological response, but with no mortality. As adults, neonatally endotoxin-treated animals exhibited significantly greater adrenocorticotrophic hormone (ACTH) and corticosterone responses to restraint stress than controls. In addition, dexamethasone pretreatment was less effective in suppressing ACTH responses to restraint stress in endotoxin-treated animals than in controls, suggesting decreased negative-feedback sensitivity to glucocorticoids. Neonatal endotoxin treatment elevated resting-state median eminence levels of corticotropin-releasing hormone (CRH) and arginine vasopressin in adult male animals, and arginine vasopressin in both adult males and females. Neonatal exposure to endotoxin also increased CRH mRNA expression in the paraventricular nucleus of the hypothalamus of adult males, with no difference in females. Finally, glucocorticoid receptor density was reduced across a wide range of brain regions in the neonatal endotoxin-treated, adult animals. These data illustrate the interactive nature of immune and endocrine systems during development. It appears that endotoxin exposure during critical stages of development decreases glucocorticoid negative-feedback inhibition of ACTH secretagogue synthesis, thus increasing HPA responsiveness to stress. The implication of these findings is that exposure to gram-negative LPS in early life can alter the development of neural systems which govern endocrine responses to stress and may thereby predispose individuals to stress-related pathology.

Authors+Show Affiliations

Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7823142

Citation

Shanks, N, et al. "Neonatal Endotoxin Exposure Alters the Development of the Hypothalamic-pituitary-adrenal Axis: Early Illness and Later Responsivity to Stress." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 15, no. 1 Pt 1, 1995, pp. 376-84.
Shanks N, Larocque S, Meaney MJ. Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary-adrenal axis: early illness and later responsivity to stress. J Neurosci. 1995;15(1 Pt 1):376-84.
Shanks, N., Larocque, S., & Meaney, M. J. (1995). Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary-adrenal axis: early illness and later responsivity to stress. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 15(1 Pt 1), 376-84.
Shanks N, Larocque S, Meaney MJ. Neonatal Endotoxin Exposure Alters the Development of the Hypothalamic-pituitary-adrenal Axis: Early Illness and Later Responsivity to Stress. J Neurosci. 1995;15(1 Pt 1):376-84. PubMed PMID: 7823142.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary-adrenal axis: early illness and later responsivity to stress. AU - Shanks,N, AU - Larocque,S, AU - Meaney,M J, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 376 EP - 84 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 15 IS - 1 Pt 1 N2 - The long-term consequences of neonatal endotoxin exposure on hypothalamic-pituitary-adrenal axis (HPA) function were assessed in adult female and male Long-Evans rats. At 3 and 5 d of age, pups were administered endotoxin (Salmonella enteritidis, 0.05 mg/kg, i.p.) at a dose that provokes a rapid and sustained physiological response, but with no mortality. As adults, neonatally endotoxin-treated animals exhibited significantly greater adrenocorticotrophic hormone (ACTH) and corticosterone responses to restraint stress than controls. In addition, dexamethasone pretreatment was less effective in suppressing ACTH responses to restraint stress in endotoxin-treated animals than in controls, suggesting decreased negative-feedback sensitivity to glucocorticoids. Neonatal endotoxin treatment elevated resting-state median eminence levels of corticotropin-releasing hormone (CRH) and arginine vasopressin in adult male animals, and arginine vasopressin in both adult males and females. Neonatal exposure to endotoxin also increased CRH mRNA expression in the paraventricular nucleus of the hypothalamus of adult males, with no difference in females. Finally, glucocorticoid receptor density was reduced across a wide range of brain regions in the neonatal endotoxin-treated, adult animals. These data illustrate the interactive nature of immune and endocrine systems during development. It appears that endotoxin exposure during critical stages of development decreases glucocorticoid negative-feedback inhibition of ACTH secretagogue synthesis, thus increasing HPA responsiveness to stress. The implication of these findings is that exposure to gram-negative LPS in early life can alter the development of neural systems which govern endocrine responses to stress and may thereby predispose individuals to stress-related pathology. SN - 0270-6474 UR - https://www.unboundmedicine.com/medline/citation/7823142/Neonatal_endotoxin_exposure_alters_the_development_of_the_hypothalamic_pituitary_adrenal_axis:_early_illness_and_later_responsivity_to_stress_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=7823142 DB - PRIME DP - Unbound Medicine ER -