Integrin alphav and NCAM mediate the effects of GDNF on DA neuron survival, outgrowth, DA turnover and motor activity in rats.

Glial cell line-derived neurotrophic factor (GDNF) is a specific neurotrophic factor for midbrain dopamine (DA) neurons, but the mechanism underlying the neurotrophic action of GDNF is not well known. The cell adhesion molecules integrin and Neural cell adhesion molecule (NCAM) play important roles in neurite outgrowth and fasciculation. In the present study, we found that subchronic GDNF administration to the pars compacta of substantia nigra in rats increased the expression of integrin alphav and NCAM. Immunostaining results demonstrated the wide distribution of integrin alphav and NCAM in all mesencephalic neurons. The results also demonstrated the co-expression of TH with integrin alphav and NCAM in the same neurons of mesencephalic culture. Further, GDNF significantly increased integrin alphav expression in single TH-positive neurons. Function-blocking anti-integrin alphav and anti-NCAM antibodies antagonized the effects of GDNF on DA neuron survival, outgrowth, DA turnover, and locomotor activity in rats. These results demonstrate that integrin alphav and NCAM mediate the effects of GDNF on DA neuron survival and outgrowth during development and on DA turnover and motor function during adulthood.