Restoration of decreased N-methyl-D-asparate receptor activity by brain-derived neurotrophic factor in the cultured hippocampal neurons: Involvement of cAMP

Brain-derived neurotrophic factor (BDNF) may play an important role in the modulation of N-methyl-D-asparate (NMDA) receptor function. To elucidate th e underlying mechanisms, whole-cell patch-clamp recording was used to asses s the effect of BDNF on the responses of cultured hippocampal neurons to th e glutamate receptor agonist NMDA. We found that peak amplitude of NMDA-evo ked currents in cultured hippocampal pyramidal neurons at Day 18 in vitro d ecreased significantly compared to that of NMDA c rents at Day 10 or 14. In terestingly, NMDA-evoked currents were greatly enhanced by BDNF (50 ng/ml) in cultured neurons at Day 18, but not at Day 10 or 14. Treatment with Rp-c AMP abolished the potentiating effects of BDNF on NMDA current. Elevating t he amount of cytosolic cAMP by preincubation with forskolin or Sp-cAMP also enhanced NMDA currents as effectively as BDNF in 18-day-old hippocampal. n eurons. Measurement of the cellular content of cAMP by RIA indicated that c ultured hippocampal neurons showed decreased basal cAMP levels at the time NMDA currents were decreased and BDNF increased the decreased cAMP levels. Taken together, these results suggest that BDNF may restore decreased NMDA receptor activity in cultured hippocampal neurons by the cAMP pathway. (C) 2001 Academic Press.