DISTRIBUTION OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) PROTEIN AND MESSENGER-RNA IN THE NORMAL ADULT-RAT CNS - EVIDENCE FOR ANTEROGRADE AXONAL-TRANSPORT

A sensitive immunohistochemical technique was used, along with highly specific affinity-purified antibodies to brain-derived neurotrophic fa ctor (BDNF), to generate a detailed mapping of BDNF immunoreactivity ( BDNF-ir) throughout the adult rat CNS. A parallel analysis of sites of BDNF synthesis was performed with in situ hybridization techniques us ing a cRNA probe to the exon encoding mature rat BDNF protein. These c ombined data revealed (1) groups of cell bodies containing diffuse BDN F-ir throughout the CNS that were strongly correlated with fields of c ells containing BDNF mRNA; (2) varying degrees of BDNF-ir outside of c ell bodies, in what appeared to be fibers and/or terminals; and (3) ma ny regions containing extremely heavy BDNF-immunoreactive fiber/termin al labeling what lacked BDNF mRNA (e.g., medial habenula, central nucl eus of the amygdala, bed nucleus of stria terminalis, lateral septum, and spinal cord). The latter observation suggested that in these regio ns BDNF was derived from anterograde axonal transport by afferent syst ems. In the two cases in which this hypothesis was tested by the elimi nation of select afferents, BDNF immunostaining was completely elimina ted. These data, along with the observation that BDNF-ir was rarely fo und within dendrites or fibers en passage, suggest that BDNF protein p roduced in adult CNS neurons is polarized primarily along axonal proce sses and is preferentially stored in terminals within the innervation target.