Neurotrophin-4/5 protects hippocampal and cortical neurons against energy deprivation- and excitatory amino acid-induced injury.
Neurotrophin-4/5 (NT-4/5) is a recently discovered member of the neurotrophin family of neurotrophic factors which includes NGF, BDNF and NT-3. NT-4/5 is expressed in the brain where its function is unknown. We have found that NT-4/5 can protect cultured embryonic rat hippocampal and cortical neurons against glucose deprivation-induced injury. Significant protection was observed with NT-4/5 concentrations from 100-1000 ng/ml, with a dose-response curve similar to that of BDNF. Neuronal vulnerability to glutamate toxicity was significantly reduced in cultures pretreated with NT-4/5. Moreover, neurons pretreated with NT-4/5 were more resistant to toxicity induced by calcium ionophore A23187, demonstrating that NT-4/5 increases neuronal resistance to calcium-mediated injury. These data indicate that, as with other neurotrophins, NT-4/5 may serve a neuroprotective function in the brain.
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536-0230.
B
B
Cheng
Y
Y
Goodman
J G
JG
Begley
M P
MP
Mattson
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D018846:Excitatory Amino Acids / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005947:Glucose / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D018846:Excitatory Amino Acids; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C071951:neurotrophin 5; D000001:Calcimycin; D005947:Glucose; C073922:neurotrophin 4; D002118:Calcium