Reelin haploinsufficiency and late-adolescent corticosterone treatment induce long-lasting and female-specific molecular changes in the dorsal hippocampus

Schroeder, Anna, Van den Buuse, Maarten, and Hill, Rachel A. (2018) Reelin haploinsufficiency and late-adolescent corticosterone treatment induce long-lasting and female-specific molecular changes in the dorsal hippocampus. Brain Sciences, 8 (7).

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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 (GAD(67)) 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.

Item ID: 55029
Item Type: Article (Research - C1)
ISSN: 2076-3425
Keywords: reelin, corticosterone, glucocorticoid receptors, NMDA receptors, parvalbumin, GAD(67)
Copyright Information: 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).
Date Deposited: 15 Aug 2018 07:39
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320999 Neurosciences not elsewhere classified @ 100%
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