Androgen modulates N-methyl-D-aspartate-mediated depolarization in CA1 hippocampal pyramidal cells

Wendy A. Pouliot, Robert J. Handa, Sheryl G. Beck

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Previously, research elucidating steroid hormone actions in the central nervous system has focused on their role in sexual reproduction and maintaining homeostasis. The hippocampus is a target of steroid modulation and is involved in the development of emotional behavior and memory storage. Area CA1 of the hippocampus contains a high density of androgen receptor (AR) and N-methyl-D-aspartate (NMDA) receptors. NMDA receptors underlie excitatory synaptic transmission and excitotoxicity in CA1 neurons. The effects of AR activation on the neurophysiology of hippocampal pyramidal neurons is unknown. Standard intracellular recording techniques in hippocampal slices were used to investigate the effects of the non-aromatizable androgen, 5-α- dihydrotestosterone-proprionate (DHTP), on CA1 pyramidal cell characteristics and NMDA receptor-mediated responses. Male Sprague-Dawley rats were unoperated, sham-operated (SHAM), gonadectomized (GDX), or gonadectomized with DHTP replacement therapy (GDX + DHTP). Neuronal AR was saturated by DHTP treatment as determined by binding studies and immunocytochemistry. Chronic DHTP treament increased the action potential duration and decreased the fast after hyperpolarization (fAHP) amplitude. To test the effect of DHTP on glutamate receptor-mediated responses, hippocampal slices were exposed to increasing concentrations of NMDA. In pyramidal cells from SHAM and GDX- treated animals, 30 μM NMDA induced an irreversible depolarization; the membrane potential of pyramidal cells from GDX + DHTP-treated animals recovered to baseline. The effect of DHTP was time dependent, implicating protein synthetic mechanisms. Our findings demonstrate that androgens can influence pyramidal cell characteristics and neurotransmitter-evoked actions in hippocampal CA1 pyramidal cells.

Original languageEnglish (US)
Pages (from-to)10-19
Number of pages10
JournalSynapse
Volume23
Issue number1
DOIs
StatePublished - May 1 1996
Externally publishedYes

Keywords

  • Dihydrotestosterone
  • Excitotoxicity
  • Hippocampus
  • N-methyl-D-aspartate

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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