Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep

Hough, D., Bellingham, M. , Haraldsen, I.R.H., McLaughlin, M. , Rennie, M., Robinson, J.E. , Solbakk, A.K. and Evans, N.P. (2017) Spatial memory is impaired by peripubertal GnRH agonist treatment and testosterone replacement in sheep. Psychoneuroendocrinology, 75, pp. 173-182. (doi:10.1016/j.psyneuen.2016.10.016) (PMID:27837697) (PMCID:PMC5140006)

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Abstract

Chronic gonadotropin-releasing hormone agonist (GnRHa) is used therapeutically to block activity within the reproductive axis through down-regulation of GnRH receptors within the pituitary gland. GnRH receptors are also expressed in non-reproductive tissues, including areas of the brain such as the hippocampus and amygdala. The impact of long-term GnRHa-treatment on hippocampus-dependent cognitive functions, such as spatial orientation, learning and memory, is not well studied, particularly when treatment encompasses a critical window of development such as puberty. The current study used an ovine model to assess spatial maze performance and memory of rams that were untreated (Controls), had both GnRH and testosterone signaling blocked (GnRHa-treated), or specifically had GnRH signaling blocked (GnRHa-treated with testosterone replacement) during the peripubertal period (8, 27 and 41 weeks of age). The results demonstrate that emotional reactivity during spatial tasks was compromised by the blockade of gonadal steroid signaling, as seen by the restorative effects of testosterone replacement, while traverse times remained unchanged during assessment of spatial orientation and learning. The blockade of GnRH signaling alone was associated with impaired retention of long-term spatial memory and this effect was not restored with the replacement of testosterone signaling. These results indicate that GnRH signaling is involved in the retention and recollection of spatial information, potentially via alterations to spatial reference memory, and that therapeutic medical treatments using chronic GnRHa may have effects on this aspect of cognitive function.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robinson, Dr Jane and Bellingham, Dr Michelle and Rennie, Mr Michael and Evans, Professor Neil and McLaughlin, Dr Mark and Hough, Dr Denise
Authors: Hough, D., Bellingham, M., Haraldsen, I.R.H., McLaughlin, M., Rennie, M., Robinson, J.E., Solbakk, A.K., and Evans, N.P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Psychoneuroendocrinology
Publisher:Elsevier
ISSN:0306-4530
Published Online:21 October 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Psychoneuroendocrinology 75: 173-182
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
536311Effects of GnRH blockade on neurocognitive and physiological endpoints.Neil EvansBiotechnology and Biological Sciences Research Council (BBSRC)BB/K002821/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED