TITLE:
Unilateral Fimbria/Fornix Transection Prevents the Synaptoplastic Effect of Dehydroepiandrosterone in the Hippocampus of Female, but Not Male, Rats
AUTHORS:
Ari L. Mendell, Neil J. MacLusky, Csaba Leranth
KEYWORDS:
Dehydroepiandrosterone; Subcortical Mediation; Synaptic Plasticity; Hippocampus; Sex Differences
JOURNAL NAME:
Neuroscience and Medicine,
Vol.4 No.3,
September
10,
2013
ABSTRACT: Dehydroepiandrosterone (DHEA), the
most abundant adrenal androgen in primates, is also synthesized from cholesterol
in the brain. Like testosterone, DHEA induces spine synapse formation in the
hippocampus. In female rats, this response is blocked by co-administration of an inhibitor of aromatase, the
enzyme responsible for estrogen biosynthesis. In males, by contrast, the hippocampal
synaptic response to DHEA is unaffected by treatment with an aromatase inhibitor. We hypothesized that this sex
difference might reflect differential dependence of the hippocampal responses
on subcortical afferents from the basal forebrain. To test this hypothesis, we
examined the effects of unilateral fimbria/ fornix transection (FFX) on
DHEA-induced synapse formation in the cornu ammonis 1 (CA1) hippocampal subfield
of gonadectomized female and male rats. In ovariectomized females, CA1 spine synapse
density after DHEA treatment was reduced by more than 60% ipsilateral to FFX. In
males, however, unilateral FFX transection had no effect on spine synapse
density after DHEA treatment. These results suggest that sex differences in the
dependence on local estrogen biosynthesis of the CA1 synaptic response to
androgen may at least in part be the result of sex differences in the relative
contributions of afferents to the hippocampus from the basal forebrain.