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Brain Sci. 2018, 8(7), 118; https://doi.org/10.3390/brainsci8070118

Reelin Haploinsufficiency and Late-Adolescent Corticosterone Treatment Induce Long-Lasting and Female-Specific Molecular Changes in the Dorsal Hippocampus

1
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3052, Australia
2
Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton 3168, Australia
3
School of Psychology and Public Health, La Trobe University, Bundoora 3086 Australia
4
Department of Pharmacology, University of Melbourne, Parkville 3052, Australia
5
The College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville 4810, Australia
*
Author to whom correspondence should be addressed.
Received: 21 May 2018 / Revised: 20 June 2018 / Accepted: 22 June 2018 / Published: 25 June 2018
(This article belongs to the Special Issue Sex Differences in the Healthy and Diseased Brain)
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Abstract

Reelin depletion and stress seem to affect similar pathways including GABAergic and glutamatergic signaling and both are implicated in psychiatric disorders in late adolescence/early adulthood. The interaction between reelin depletion and stress, however, remains unclear. To investigate this, male and female heterozygous reelin mice (HRM) and wildtype (WT) controls were treated with the stress hormone, corticosterone (CORT), during late adolescence to simulate chronic stress. Glucocorticoid receptors (GR), N-methyl-d-aspartate receptor (NMDAr) subunits, glutamic acid decarboxylase (GAD67) and parvalbumin (PV) were measured in the hippocampus and the prefrontal cortex (PFC) in adulthood. While no changes were seen in male mice, female HRM showed a significant reduction in GR expression in the dorsal hippocampus. In addition, CORT reduced GR levels as well as GluN2B and GluN2C subunits of NMDAr in the dorsal hippocampus in female mice only. CORT furthermore reduced GluN1 levels in the PFC of female mice. The combined effect of HRM and CORT treatment appeared to be additive in terms of GR expression in the dorsal hippocampus. Female-specific CORT-induced changes were associated with overall higher circulating CORT levels in female compared to male mice. This study shows differential effects of reelin depletion and CORT treatment on GR and NMDAr protein expression in male and female mice, suggesting that females are more susceptible to reelin haploinsufficiency as well as late-adolescent stress. These findings shed more light on female-specific vulnerability to stress and have implications for stress-associated mental illnesses with a female bias including anxiety and major depression. View Full-Text
Keywords: reelin; corticosterone; glucocorticoid receptors; NMDA receptors; parvalbumin; GAD67 reelin; corticosterone; glucocorticoid receptors; NMDA receptors; parvalbumin; GAD67
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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 (CC BY 4.0).
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Schroeder, A.; van den Buuse, M.; Hill, R.A. Reelin Haploinsufficiency and Late-Adolescent Corticosterone Treatment Induce Long-Lasting and Female-Specific Molecular Changes in the Dorsal Hippocampus. Brain Sci. 2018, 8, 118.

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