Localization of Brain-Derived Neurotrophic Factor and Neurotrophin-3 RNA Transcripts in the Brain of Reeler, Weaver and pcd Mutant Mice

The pattern of BDNF and neurotrophin-3 (NT-3) gene expression was analyzed in the cerebellum of wild-type (+ / +), reeler (rl/rl), weaver (wv/wv) and 'Purkinje cell degeneration' (pcd/pcd) mice by in situ hybridization histochemistry. [^<32>P] Labeled synthetic oligonucleotide DNA probes were used, complementary to bases 219-266 and 777-824 of the published mouse BDNF cDNA sequence and to bases 91-138 and 235-288 of the rat NT-3 genomic sequence. Previous developmental studies in rat cerebellum point to a possible involvement of NT-3 in early migratory and synaptogenetic events and of BDNF as a maintenance factor at later stages. In the wild-type mice, strong mRNA hybridization signals were obtained for both BDNF and NT-3 in the cerebellar granule cell layer. Reeler and weaver mice showed remarkable reductions for both BDNF and NT-3 mRNA hybridization signals in the cerebellum, which is readily explainable by the genetically-determined granule cell loss. The cerebellum of pcd mice, which primarily lose Purkinje cells, showed a slight reduction in BDNF and NT-3 mRNAs. Reeler homozygotes also showed a substantial decrease of the BDNF RNA message in the pyramidal cell layer of hippocampal CA1 field; in the cerebral cortex, the lamination was not as evident as that in normal mice. The changes recorded in BDNF and NT-3 RNA messages in these mutants are consistent with the localization of nerve cell losses. Nonetheless, their roles and possible involvement in early developmental or degenerative events remain open. These results could also suggest a coordinated down-regulation of these genes subsequent to the degeneration of Purkinje cells