Neurobehavioral and molecular changes in a rodent model of ACTH-induced HPA axis dysfunction.

Autor: Sallie FN; Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa., Pienaar L; Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa., Lubbe A; Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa., Xhakaza S; Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa., Manne SR; Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa., de la Torre BG; Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa., Albericio F; Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa., Mu Daniels W; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa., Me Millen A; Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa. Electronic address: aletta.millen@wits.ac.za., Baijnath S; Wits Integrated Molecular Physiology Research Initiative, Wits Health Consortium (PTY) Ltd, School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; School of Physiology, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa. Electronic address: sooraj.baijnath@wits.ac.za.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2024 Jul 01; Vol. 1834, pp. 148913. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1016/j.brainres.2024.148913
Abstrakt: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is linked to the pathophysiology of depression. Although exogenous adrenocorticotropic hormone (ACTH) is associated with a depressive-like phenotype in rodents, comprehensive neurobehavioral and mechanistic evidence to support these findings are limited. Sprague-Dawley rats (male, n = 30; female, n = 10) were randomly assigned to the control (male, n = 10) or ACTH (male, n = 20; female n = 10) groups that received saline (0.1 ml, sc.) or ACTH (100 μg/day, sc.), respectively, for two weeks. Thereafter, rats in the ACTH group were subdivided to receive ACTH plus saline (ACTH_S; male, n = 10; female, n = 5; 0.2 ml, ip.) or ACTH plus imipramine (ACTH_I; male, n = 10; female, n = 5;10 mg/kg, ip.) for a further four weeks. Neurobehavioral changes were assessed using the forced swim test (FST), the sucrose preference test (SPT), and the open field test (OFT). Following termination, the brain regional mRNA expression of BDNF and CREB was determined using RT-PCR. After two-weeks, ACTH administration significantly increased immobility in the FST (p = 0.03), decreased interaction with the center of the OFT (p < 0.01), and increased sucrose consumption (p = 0.03) in male, but not female rats. ACTH administration significantly increased the expression of BDNF in the hippocampus and CREB in all brain regions in males (p < 0.05), but not in female rats. Imipramine treatment did not ameliorate these ACTH-induced neurobehavioral or molecular changes. In conclusion, ACTH administration resulted in a sex-specific onset of depressive-like symptoms and changes in brain regional expression of neurotrophic factors. These results suggest sex-specific mechanisms underlying the development of depressive-like behavior in a model of ACTH-induced HPA axis dysregulation.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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