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Volume 17, Number 7, Issue of April 1, 1997 pp. 2295-2313
Copyright ©1997 Society for NeuroscienceDistribution of Brain-Derived Neurotrophic Factor (BDNF) Protein and mRNA in the Normal Adult Rat CNS: Evidence for Anterograde Axonal Transport
Received Aug. 9, 1996; revised Dec. 12, 1996; accepted Jan. 17, 1997.
James M. Conner1, Julie C. Lauterborn2, Qiao Yan3, Christine M. Gall2, and Silvio Varon1 1 Department of Biology, 0506, University of California, San Diego, La Jolla, California 92093, 2 Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, and 3 Amgen Center, Thousand Oaks, California 91320
A sensitive immunohistochemical technique was used, along with highly specific affinity-purified antibodies to brain-derived neurotrophic factor (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 using a cRNA probe to the exon encoding mature rat BDNF protein. These combined data revealed (1) groups of cell bodies containing diffuse BDNF-ir throughout the CNS that were strongly correlated with fields of cells containing BDNF mRNA; (2) varying degrees of BDNF-ir outside of cell bodies, in what appeared to be fibers and/or terminals; and (3) many regions containing extremely heavy BDNF-immunoreactive fiber/terminal labeling that lacked BDNF mRNA (e.g., medial habenula, central nucleus of the amygdala, bed nucleus of stria terminalis, lateral septum, and spinal cord). The latter observation suggested that in these regions BDNF was derived from anterograde axonal transport by afferent systems. In the two cases in which this hypothesis was tested by the elimination of select afferents, BDNF immunostaining was completely eliminated. These data, along with the observation that BDNF-ir was rarely found within dendrites or fibers en passage, suggest that BDNF protein produced in adult CNS neurons is polarized primarily along axonal processes and is preferentially stored in terminals within the innervation target.
Key words: neurotrophin; immunohistochemistry; in situ hybridization; neurotrophic factor; BDNF; anterograde axonal transport
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