Down-regulation of serum gonadotropins is as effective as estrogen replacement at improving menopause-associated cognitive deficits.

Abstract:

:Declining levels of estrogen in women result in increases in gonadotropins such as luteinizing hormone (LH) through loss of feedback inhibition. LH, like estrogen, is modulated by hormone replacement therapy. However, the role of post-menopausal gonadotropin increases on cognition has not been evaluated. Here, we demonstrate that the down-regulation of ovariectomy-driven LH elevations using the gonadotropin releasing hormone super-analogue, leuprolide acetate, improves cognitive function in the Morris water maze and Y-maze tests in the absence of E2. Furthermore, our data suggest that these effects are independent of the modulation of estrogen receptors alpha and beta, or activation of CYP19 and StAR, associated with the production of endogenous E2. Importantly, pathways associated with improved cognition such as CaMKII and GluR1-Ser831 are up-regulated by leuprolide treatment but not by chronic long-term E2 replacement suggesting independent cognition-modulating properties. Our findings suggest that down-regulation of gonadotropins is as effective as E2 in modulating cognition but likely acts through different molecular mechanisms. These findings provide a potential novel protective strategy to treat menopause/age-related cognitive decline and/or prevent the development of AD.

journal_name

J Neurochem

authors

Bryan KJ,Mudd JC,Richardson SL,Chang J,Lee HG,Zhu X,Smith MA,Casadesus G

doi

10.1111/j.1471-4159.2009.06502.x

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

870-81

issue

4

eissn

0022-3042

issn

1471-4159

pii

JNC6502

journal_volume

112

pub_type

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