Effects of methylprednisolone on the GABA- and glutamate-induced currents: relevance to glucocorticoid-induced neurotoxicity and brain aging.

We have previously shown that both epidural administration and microinjection of methylprednisolone (MP) produces neuronal hyperexcitability in the murine spinal cord in vivo. In this study, the whole-cell patch-clamp technique was used to describe and characterize MP-induced neuronal hyperexcitability. Exposure of 10- to 18-day old dissociated spinal cord cultures to 65 microM-8 mM MP caused a concentration-dependent increase in the firing rate. MP (1 mM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs). The amplitude of the sEPSCs was also increased in response to 1 mM MP, whereas sIPSCs became smaller in size in the presence of MP. MP (1 mM) reduced the amplitude of the gamma-aminobutyric acid (GABA)-induced currents, whereas it increased the amplitude of the glutamate-induced currents. And finally; MP (1 mM), by itself, did not change the overall postsynaptic membrane conductance. These observations suggest that (1) MP can act as an excitatory agent in vitro, (2) it can act at the presynaptic as well as the postsynaptic level, and (3) it affects spinal cord neurons by influencing the ligand-gated (GABA and glutamate) channels.