GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR PROTECTS STRIATAL CALBINDIN-IMMUNOREACTIVE NEURONS FROM EXCITOTOXIC DAMAGE

The neostriatum is one of the areas with relatively high levels of gli al cell line-derived neurotrophic factor (GDNF) messenger RNA expressi on in the developing and adult brain. GDNF expression in the neostriat um has been suggested to be involved in promoting the survival of nigr al dopaminergic neurons, acting as a target-derived neurotrophic facto r. However, GDNF messenger RNA expression in the striatum starts sever al days before dopaminergic and other afferent neurons reach the stria tum, suggesting additional trophic effects of this factor on striatal neurons. In the present report, we have examined whether GDNF is able to prevent the degeneration of striatal calbindin- and parvalbumin-imm unoreactive neurons in a lesion model of Huntington's disease. Fischer 344 rat 3T3 fibroblast cell Line expressing high levels of GDNF (F3A- GDNF) was used to assess the protective effect of this factor, on stri atal neurons, against excitotoxicity. Quinolinate (34 nmol) was inject ed at two different coordinates, and calbindin, parvalbumin and tyrosi ne hydroxylase immunoreactivity were examined seven days after lesion. Dopaminergic afferents were spared after quinolinate injection, but t he number of calbindin- and parvalbumin-immunoreactive neurons was dec reased. Interestingly, implantation of F3A-GDNF cells increased the de nsity of tyrosine hydroxylase staining in the intact and also in the q uinolinate-lesioned striatum. Furthermore, GDNF partially protected ca lbindin- but not parvalbumin-immunoreactive neurons from quinolinate e xcitotoxicity. Instead, mock-transfected fibroblasts did not affect an y of these parameters. Our results show that GDNF specifically protect s a subpopulation of striatal calbindin-immunoreactive neurons against quinolinate lesion, suggesting that GDNF administration may have a po tential therapeutic application in the prevention and treatment of str iatonigral degenerative disorders. Copyright (C) 1996 IBRO.