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 the underlying mechanisms, whole-cell patch-clamp recording was used to assess the effect of BDNF on the responses of cultured hippocampal neurons to the glutamate receptor agonist NMDA. We found that peak amplitude of NMDA-evoked currents in cultured hippocampal pyramidal neurons at Day 18 in vitro decreased significantly compared to that of NMDA currents at Day 10 or 14. Interestingly, 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-cAMP abolished the potentiating effects of BDNF on NMDA current. Elevating the amount of cytosolic cAMP by preincubation with forskolin or Sp-cAMP also enhanced NMDA currents as effectively as BDNF in 18-day-old hippocampal neurons. Measurement of the cellular content of cAMP by RIA indicated that cultured 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.
Sun
J H
JH
Department of Physiology, Second Military Medical University, Shanghai, 200433, People's Republic of China. jhsun@smmu.edu.cn
Yan
X Q
XQ
Xiao
H
H
Zhou
J W
JW
Chen
Y Z
YZ
Wang
C A
CA
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D016202:N-Methylaspartate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases