Brain-derived neurotrophic factor prevents neuronal cell death induced by corticosterone.
Corticosterone (CORT), one of the glucocorticoids, causes neuronal damage in the hippocampus, but the mechanism(s) of action underlying its effects remains unknown. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that belongs to the neurotrophin family, affects the survival and/or differentiation of various types of neurons in vitro, and is able to antagonize neuronal death induced by various brain insults or neurotoxins in vivo. In this study, the effects of CORT on BDNF protein contents and mRNA expression were investigated in relation to neuronal survival/death of cultured rat hippocampal neurons, because the colocalization of BDNF with its receptor, TrkB, suggests that BDNF may exert its putative protective and trophic effects through an autocrine mechanism in the hippocampus. Administration of CORT accelerated the neuronal death that proceeds after serum deprivation, and simultaneously reduced the levels of BDNF mRNA and intracellular BDNF content. Exogenously added BDNF actually attenuated CORT-induced neuronal death, but not in the presence of K252a, an inhibitor of the tyrosine kinase activity of Trk family receptors. These observations suggest that CORT induces damage to hippocampal neurons, at least partly, via reducing their BDNF synthesis.
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-Higashi, Gifu, Japan.
A
A
Nitta
M
M
Ohmiya
A
A
Sometani
M
M
Itoh
H
H
Nomoto
Y
Y
Furukawa
S
S
Furukawa
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics*; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003345:Corticosterone / Q000633:toxicity*; D017931:DNA Primers; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D007124:Immunoenzyme Techniques; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D003345:Corticosterone