Gene therapy using IGF-1 & GDNF in the dopaminergic neurons of senile rats

MOREL GR; HEREÑU CB; GOYA RG

Ottawa

Congreso; 4th Canadian Neuroscience meeting; 2010

Canadian Association for Neuroscience

Degeneration and loss of (dopaminergic) hypothalamus DA neurons during normal aging is associated, in the female rat, with a progressive hyperprolactinemia and the development of pituitary prolactinomas. This neuroendocrine pathology provides a unique animal model to assess the efficacy of therapeutic strategies aimed at protecting central DA neurons. There is clear evidence that IGF-I plays a physiologic role in neuroprotection. In recent studies we have demonstrated that IGF-I gene therapy in the hypothalamus of senile female rats is highly effective to restore hypothalamic DA neuron number and correct the chronic hyperprolactinemia associated with depressed hypothalamic DA neuron function in old rats. Glial cell line-derived neurotrophic factor (GDNF), is a the most potent neurotrofic factor tested in animal models of Parkinson disease. GDNF is also able to reduce the chronic hyperprolactinemia of senile females albeit to a lesser extent than IGF-I. Our findings suggest that the function of DA neurons in the hypothalamus of aged animals can be restored by IGF-1 and GDNF. Whether gen therapy with IGF-1 and GDNF induces DA neurogenesis in the hypothalamus and another dopaminergic neuron like the dopaminergic system remains to be investigated.