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.