Neurobiology of Aging
Volume 24, Issue 1 , Pages 105-116, January 2003

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

  • Chih Chang Chao

      Affiliations

    • Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
    • ,
  • Yun Li Ma

      Affiliations

    • Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC
    • ,
  • Kuan Yu Chu

      Affiliations

    • Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC
    • ,
  • Eminy H.Y Lee

      Affiliations

    • Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC
    • Corresponding Author InformationCorresponding author. Tel.: +886-2-2789-9125; fax: +886-2-2782-2835.

Received 11 October 2001; received in revised form 7 March 2002; accepted 25 March 2002.

Abstract 

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 αv and NCAM. Immunostaining results demonstrated the wide distribution of integrin αv and NCAM in all mesencephalic neurons. The results also demonstrated the co-expression of TH with integrin αv and NCAM in the same neurons of mesencephalic culture. Further, GDNF significantly increased integrin αv expression in single TH-positive neurons. Function-blocking anti-integrin αv 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 αv and NCAM mediate the effects of GDNF on DA neuron survival and outgrowth during development and on DA turnover and motor function during adulthood.

Keywords:  Glial cell line-derived neurotrophic factor, Substantia nigra, Integrin, NCAM, Mesencephalic culture, Dopamine

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PII: S0197-4580(02)00047-7

Neurobiology of Aging
Volume 24, Issue 1 , Pages 105-116, January 2003

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