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The Journal of Neuroscience, May 13, 2009, 29(19):6058-6067; doi:10.1523/JNEUROSCI.5253-08.2009

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Cellular/Molecular
Estradiol Reverses a Calcium-Related Biomarker of Brain Aging in Female Rats

Lawrence D. Brewer, * Amy L. S. Dowling, * Meredith A. Curran-Rauhut, Philip W. Landfield, Nada M. Porter, and Eric M. Blalock

Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky 40536

Correspondence should be addressed to either Nada M. Porter or Eric M. Blalock, Department of Molecular and Biomedical Pharmacology, 800 Rose Street UKMC/MS-315, University of Kentucky, Lexington, KY 40536 Email: nadap{at}uky.edu or Email: emblal{at}uky.edu

An increase in L-type voltage-gated calcium channel (LTCC) current is a prominent biomarker of brain aging and is believed to contribute to cognitive decline and vulnerability to neuropathologies. Studies examining age-related changes in LTCCs have focused primarily on males, although estrogen (17β-estradiol, E2) affects calcium-dependent activities associated with cognition. Therefore, to better understand brain aging in females, the effects of chronic E2 replacement on LTCC current activity in hippocampal neurons of young and aged ovariectomized rats were determined. The zipper slice preparation was used to expose cornu ammonis 1 (CA1) pyramidal neurons for recording LTCC currents using the cell-attached patch-clamp technique. We found that an age-related increase in LTCC current in neurons from control animals was prevented by E2 treatment. In addition, in situ hybridization revealed that within stratum pyramidale of the CA1 area, mRNA expression of the Cav1.2 LTCC subunit, but not the Cav1.3 subunit, was decreased in aged E2-treated rats. Thus, the reported benefits of E2 on cognition and neuronal health may be attributed, at least in part, to its age-related decrease in LTCC current.

Received Oct. 31, 2008; revised March 1, 2009; accepted April 3, 2009.

Correspondence should be addressed to either Nada M. Porter or Eric M. Blalock, Department of Molecular and Biomedical Pharmacology, 800 Rose Street UKMC/MS-315, University of Kentucky, Lexington, KY 40536 Email: nadap{at}uky.edu or Email: emblal{at}uky.edu


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