Increased anxiety-like phenotype in female guinea pigs following reduced neurosteroid exposure in utero

Cumberland, A, Palliser, H, Crombie, G, Walker, D and Hirst, J 2017, 'Increased anxiety-like phenotype in female guinea pigs following reduced neurosteroid exposure in utero', International Journal of Developmental Neuroscience, vol. 58, pp. 50-58.

Document type: Journal Article
Collection: Journal Articles

Title Increased anxiety-like phenotype in female guinea pigs following reduced neurosteroid exposure in utero
Author(s) Cumberland, A
Palliser, H
Crombie, G
Walker, D
Hirst, J
Year 2017
Journal name International Journal of Developmental Neuroscience
Volume number 58
Start page 50
End page 58
Total pages 9
Publisher Pergamon Press
Abstract Neurosteroids are essential for aiding proper fetal neurodevelopment. Pregnancy compromises such as preterm birth, prenatal stress and intrauterine growth restriction are associated with an increased risk of developing behavioural and mood disorders, particularly during adolescence. These pathologies involve the premature loss or alteration of trophic steroid hormones reaching the fetus leading to impaired neurodevelopment. While the specific programming mechanisms are yet to be fully elucidated, in adult life, dysfunctions of allopregnanolone action are prevalent in individuals with depression, post-traumatic stress disorder and anxiety disorders. The objective of this study was to assess if changes in concentrations of the neurosteroid, allopregnanolone, may be a fetal programming factor in priming the brain towards a negative behavioural phenotype during the childhood to adolescent period using a guinea pig model. Pregnant guinea pigs received either vehicle (45% (2-hydroxypropyl)-β-cyclodextrin) or the 5α-reductase inhibitor, finasteride (25 mg/kg maternal weight) from gestational age 60 until spontaneous delivery (∼71 days gestation). Male and female offspring from vehicle and finasteride treated dams were tested at postnatal day 20 (juvenile-equivalence) in an open field arena, and hippocampus and amygdala subsequently assessed for neurological changes in markers of development and GABA production pathways 24 h later. Females with reduced allopregnanolone exposure in utero displayed increased neophobic-like responses to a change in their environment compared to female controls. There were no differences in the neurodevelopmental markers assessed; MAP2, NeuN, MBP, GFAP or GAD67 between intrauterine finasteride or vehicle exposure, in either the hippocampus or amygdala whereas GAT1 staining was decreased. This study indicates that an intrauterine reduction in the supply of allopregnanolone programs vulnerability of female offspring to anxiet
Subject Foetal Development and Medicine
Neurosciences not elsewhere classified
Keyword(s) Allopregnanolone
Fetal programming
DOI - identifier 10.1016/j.ijdevneu.2017.02.001
Copyright notice © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.
ISSN 0736-5748
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
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