INTRASTRIATAL INFUSIONS OF BRAIN-DERIVED NEUROTROPHIC FACTOR - RETROGRADE TRANSPORT AND COLOCALIZATION WITH DOPAMINE-CONTAINING SUBSTANTIA-NIGRA NEURONS IN RAT

The pattern of retrogradely transported BDNF, a member of the nerve gr owth family of neurotrophins, following intrastriatal infusion was imm unohistochemically visualized within the rodent central nervous system . Human recombinant BDNF was infused at a rate of 3 mu g/h for 7 days with an Alzet 2002 minipump prior to sacrifice. Tissue immunohistochem ically processed using a turkey anti-BDNF antibody revealed retrograde ly transported BDNF within neurons located mainly within the ipsilater al frontoparietal cortex (predominantly layer V), parafascicular and p osterior thalamic nuclei, and substantia nigra, pars compacta. Section s dual immunoreacted for BDNF and tyrosine hydroxylase revealed a subp opulation of dopaminergic neurons (approximately 28%) within the pars compacta which contained retrogradely transported BDNF. Experiments in which a mixture of BDNF and the retrograde tracer fluorogold were sim ultaneously infused for 7 days into the striatum revealed BDNF and flu orogold single-labeled neurons as well as BDNF and fluorogold dual-lab eled cells within the substantia nigra, pars compacta. These observati ons indicate that only a subpopulation of neurons within the substanti a nigra retrogradely transport BDNF following intrastriatal infusion a nd thus only a subpopulation of cells may be responsive to the trophic influences of BDNF. The retrograde transport of trophins, such as BDN F, represents a unique neuroanatomical tool to selectivity map the loc ation of specific neurotrophin-responsive systems. Unraveling the trop hic anatomy of BDNF will aid in understanding its role in development, degeneration, and experimental animal models of regeneration providin g essential data for its use in clinical neurodegenerative disorders i ncluding Parkinson's disease. (C) 1994 Academic Press, Inc.