Cerebellar changes in guinea pig offspring following suppression of neurosteroid synthesis during late gestation

Cumberland, A, Palliser, H, Walker, D and Hirst, J 2017, 'Cerebellar changes in guinea pig offspring following suppression of neurosteroid synthesis during late gestation', Cerebellum, vol. 16, no. 2, pp. 306-313.


Document type: Journal Article
Collection: Journal Articles

Title Cerebellar changes in guinea pig offspring following suppression of neurosteroid synthesis during late gestation
Author(s) Cumberland, A
Palliser, H
Walker, D
Hirst, J
Year 2017
Journal name Cerebellum
Volume number 16
Issue number 2
Start page 306
End page 313
Total pages 8
Publisher Springer New York
Abstract Elevated gestational concentrations of allopregnanolone are essential for the development and neuroprotection of the foetal brain. Preterm birth deprives the foetus of these high levels of allopregnanolone, which may contribute to the associated adverse effects on cerebellar development. Preterm birth alters expression of GABA A receptor subunit composition, which may further limit neurosteroid action. The objective of this study was to determine the effects of suppression of allopregnanolone levels on the markers of development and functional outcome. Pregnant guinea pigs were treated with finasteride at a dose (25 mg/kg maternal weight) shown to suppress allopregnanolone between 60 days of gestation until delivery (term ∼71 days). The cerebella from neonates, whose mothers were treated with finasteride or vehicle during pregnancy, were collected at postnatal age 8. Pups that received finasteride displayed significantly greater glial fibrillary acid protein area coverage and reduced GABA A receptor α 6 -subunit messenger RNA within the cerebellum than pups that were exposed to vehicle. These findings indicate that loss of neurosteroid action on the foetal brain in late gestation produces prolonged astrocyte activation and reductions in GABA A receptor α 6 -subunit expression. These changes may contribute to the long-term changes in function associated with preterm birth.
Subject Foetal Development and Medicine
Keyword(s) Allopregnanolone
Astrocyte
Cerebellum
Finasteride
GABA receptor A
DOI - identifier 10.1007/s12311-016-0802-0
Copyright notice © Springer Science+Business Media New York 2016
ISSN 1473-4222
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