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International Journal of Endocrinology
Volume 2018, Article ID 7231915, 12 pages
Research Article

Investigating the Interactive Effects of Sex Steroid Hormones and Brain-Derived Neurotrophic Factor during Adolescence on Hippocampal NMDA Receptor Expression

1Department of Psychiatry, School of Clinical Sciences, Monash Medical Centre, Monash University, Clayton, VIC, Australia
2The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
3Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence should be addressed to Rachel A. Hill; ude.hsanom@llih.lehcar

Received 5 June 2017; Revised 5 October 2017; Accepted 19 October 2017; Published 31 January 2018

Academic Editor: Małgorzata Kotula-Balak

Copyright © 2018 Cushla R. McCarthny et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Sex steroid hormones have neuroprotective properties which may be mediated by brain-derived neurotrophic factor (BDNF). This study sought to determine the interactive effects of preadolescent hormone manipulation and BDNF heterozygosity (+/−) on hippocampal NMDA-R expression. Wild-type and BDNF+/− mice were gonadectomised, and females received either 17β-estradiol or progesterone treatment, while males received either testosterone or dihydrotestosterone (DHT) treatment. Dorsal (DHP) and ventral hippocampus (VHP) were dissected, and protein expression of GluN1, GluN2A, GluN2B, and PSD-95 was assessed by Western blot analysis. Significant genotype × OVX interactions were found for GluN1 and GluN2 expression within the DHP of female mice, suggesting modulation of select NMDA-R levels by female sex hormones is mediated by BDNF. Furthermore, within the DHP BDNF+/− mice show a hypersensitive response to hormone treatment on GluN2 expression which may result from upstream alterations in TrkB phosphorylation. In contrast to the DHP, the VHP showed no effects of hormone manipulation but significant effects of genotype on NMDA-R expression. Castration had no effect on NMDA-R expression; however, androgen treatment had selective effects on GluN2B. These data show case distinct, interactive roles for sex steroid hormones and BDNF in the regulation of NMDA-R expression that are dependent on dorsal versus ventral hippocampal region.