DISTRIBUTION OF INTRACEREBRAL VENTRICULARLY ADMINISTERED NEUROTROPHINS IN RAT-BRAIN AND ITS CORRELATION WITH TRK RECEPTOR EXPRESSION

To assess the potential effectiveness by which injected neurotrophins can diffuse throughout the brain, we used autoradiographic and immunoh istochemical techniques to examine the brain distributions of nerve gr owth factor (NGF), brain-derived neurotrophic factor (BDNF), and neuro trophin-3 (NT-3) after a single injection into the lateral cerebral ve ntricle (ICV) in rats. As described previously, ICV-injected NGF label ed cholinergic neurons in the basal forebrain. Injection of BDNF resul ted in few or no labeled neuronsin the basal forebrain or in the subst antia nigra. However, very intense labeling was associated with the ve ntricular walls and immediate parenchyma. The distribution of NT-3 aft er ICV injection was intermediate between that of NGF and BDNF, In the basal forebrain, similar neurotrophin distributions were observed in neonate versus adult animals. Our in situ hybridization analysis has s hown that mRNA encoding the BDNF receptor(s) (trhB) is highly expresse d by ependymal cells as well as by many neurons and glia. On the other hand, expression of the high-affinity NGF receptor (trkA) is restrict ed to cholinergic neurons in basal forebrain and striatum. In addition , staining with antisera specific for the trkA or trkB receptors demon strated that their expression patterns closely reflect their mRNA dist ributions. Taken together, these data suggest that the presence of the trhB receptor on the ependymal layer of the ventricle and its express ion throughout the brain parenchyma represents a significant impedimen t to the adequate diffusion of ICV injected BDNF into the brain for de livery to target neurons. (C) 1994 Academic Press, Inc.