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Anxiety-like behavior and structural changes of the bed nucleus of the stria terminalis (BNST) in gestational protein-restricted male offspring

Published online by Cambridge University Press:  14 June 2018

D. B. Torres ,
A. Lopes ,
A. J. Rodrigues ,
J. J Cerqueira ,
N. Sousa ,
J. A. R. Gontijo  and
P. A. Boer
D. B. Torres
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
A. Lopes
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
A. J. Rodrigues
Affiliation:
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal
J. J Cerqueira
Affiliation:
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal
N. Sousa
Affiliation:
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal
J. A. R. Gontijo
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
P. A. Boer*
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
*
Address for correspondence: P. A. Boer, Department of Internal Medicine, School of Medicine, State University of Campinas, 126 Tessália Vieira de Camargo Street, 13083-887 Campinas, SP, Brazil. E-mail: alineboer@yahoo.com.br
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Abstract

Animal evidence has suggested that maternal emotional and nutritional stress during pregnancy is associated with behavioral outcomes in offspring. The nature of the stresses applied may differ, but it is often assumed that the mother’s hippocampus–hypothalamic–pituitary–adrenal (HHPA) axis response releases higher levels of glucocorticoid hormones. The bed nucleus of the stria terminalis (BNST) is in a pivotal position to regulate the HHPA axis and the stress response, and it has been implicated in anxiety behavior. In the current study, to search whether BNST structural changes and neurochemical alterations are associated with anxiety-related behavior in adult gestational protein-restricted offspring relative to an age-matched normal protein diet (NP) rats, we conduct behavioral tests and, BNST dendritic tree analysis by Sholl analysis, associated to immunoblotting–protein quantification [11β-HSD2, GR, MR, AT1R, 5HT1A and 5HT2A, corticotrophin-releasing factor (CRH) and CRH1]. Dams were maintained either on isocaloric standard rodent chow [with NP content, 17% casein or low protein content (LP), 6% casein] chow throughout their entire pregnancy. Here, in rats subjected to gestational protein restriction, we found: (a) a significant reduction in dendritic length and impoverished dendritic arborization in BNST neurons; (b) an elevated plasmatic corticosterone levels; and (c) associated with enhanced anxiety-like behavior when compared with age-matched NP offspring. Moreover, altered protein (11β-HSD2, GR, MR and type 1 CRH receptors) expressions may underlie the increase in anxiety-like behavior in LP offspring. This work represents the first demonstration that BNST developmental plasticity by maternal protein restriction, resulting in fine structural changes and neurochemical alterations that are associated with modified behavioral states.

Keywords

anxiety-like behaviorBNSTdendritic remodelingfetal programminggestational protein restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 5 , October 2018 , pp. 536 - 543
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

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