INTRASTRIATAL AND INTRAVENTRICULAR INFUSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN THE CYNOMOLOGOUS MONKEY - DISTRIBUTION, RETROGRADE TRANSPORT AND COLOCALIZATION WITH SUBSTANTIA-NIGRA DOPAMINE-CONTAINING NEURONS

The distribution and retrograde transport of brain-derived neurotrophi c factor was examined using magnetic resonance imaging guided stereota xic intracerebroventricular and intrastriatal infusion in the cynomolo gous monkey. Two intracerebroventricular animals were infused with bra in-derived neurotrophic factor at a dose of 3 mu g/h for 21 and 28 day s. A third intracerebroventricular animal received sequential infusion s of 15, 30 and 60 mu g/h brain-derived neurotrophic factor each for s even days using an Alzet 2002 minipump. For the multiple intrastriatal animals (n = 5) a dose of 3 mu g/h was infused into each site. One in trastriatal monkey was infused with vehicle solution of 10 mM phosphat e-buffered saline pH 7.4 for 14 days resulting in no brain-derived neu rotrophic factor immunoreactivity. Following the lower dose intracereb roventricular infusion, brain-derived neurotrophic factor immunoreacti vity was confined to the ventricular ependymal layer. In the sequentia l higher dose intracerebroventricular case, the cannula was located ma inly within the lateral ventricle, although there was damage to the ep endymal wall and adjacent caudate nucleus. Brain-derived neurotrophic factor immunoreactivity revealed spread of injectate within the ipsila teral and to a lesser extent the contralateral caudate nucleus, septum , orbital cortex and ventricular ependymal wall. In this case, retrogr adely labelled brain-derived neurotrophic factor neurons were found wi thin the parafascicular thalamus and substantia nigra, pars compacta, as well as within cortex, vertical limb of the diagonal band and nucle us basalis. Brain-derived neurotrophic factor intrastriatal infusion r etrogradely labelled perikarya within sensory motor cortex, parafascic ular thelamus and substantia nigra, pars compacta. Sections from these cases dual-immunoreacted for brain-derived neurotrophic factor and ty rosine hydroxylase, the synthesizing enzyme for dopamine, revealed a s ubpopulation of pars compacta dopaminergic neurons which contained ret rogradely transported brain-derived neurotrophic factor. These finding s indicate that a select subgroup of nigral dopamine neurons retrograd ely transport brain-derived neurotrophic factor in the primate. Furthe rmore it remains to be determined whether select nigral cells are resp onsive to the trophic influences of brain-derived neurotrophic factor in the normal and neuropathologic condition.