We have recently shown that chronic neurosteroid, 5α 3α, treatment produced down-regulation of the GABA receptor binding and function, and heterologous uncoupling on the GABA(A) receptor complex in cultured mammalian cortical neurons. In order to explore the underlying mechanism of these observed down-regulation and heterologous uncoupling phenomenon, we investigated the effect of chronic 5α 3α (1 μM; 5 days) treatment on the GABA(A) receptor subunits mRNA levels, using RNase protection assay. We found that chronic neurosteroid, 5α 3α, treatment decreased the β- and α-subunits mRNA levels while not altering the γ2S-subunit mRNA levels in the cortical neurons. The decrease in the β-subunits mRNA levels suggests a decrease in the presence of the β-subunits in the composition of GABA, receptors. This phenomenon may explain the down-regulation of the GABA, receptor binding and function. A decrease in the α3-subunit mRNA level suggests a corresponding decrease in the α3-subunit in the composition of GABA(A) receptor isoforms, relative to other isoforms. This observation may be responsible for the chronic neurosteroid-induced uncoupling and decreased efficacy. In summary, chronic 5α 3α treatment produced down-regulation of the GABA(A) receptor β- and α3-subunit mRNA levels, and these changes may be associated with the down-regulation, heterologous uncoupling, and decreased efficacy of GABA(A) receptor complex in the cultured mammalian cortical neurons.
- Chronic neurosteroid treatment
- Down-regulation of subunit mRNA
- GABA(A) receptor subunit
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience