ALTERATIONS IN HIPPOCAMPAL EXPRESSION OF SNAP-25, GAP-43, STANNIN ANDGLIAL FIBRILLARY ACIDIC PROTEIN FOLLOWING MECHANICAL AND TRIMETHYLTIN-INDUCED INJURY IN THE RAT

A set of well-defined antisera against neuronal and glial proteins wer e used to characterize patterns of protein expression in rat hippocamp us following transection of the fimbira-fornix and perforant pathways or after administration of the selective neurotoxicant trimethylin (8 mg/kg, i.p.). SNAP-25 (synaptosomal protein, mol. wt 25000) is a neuro n-specific, developmentally regulated presynaptic protein, stannin is a protein enriched in cells sensitive to trimethyltin, and GAP-43 (gro wth-associated protein, mol. wt 43000) is associated with axonal growt h and regeneration. Glial fibrillary acidic protein is an astrocyte-sp ecific intermediate filament protein and a marker for reactive gliosis . SNAP-25 immunoreactivity was altered following both neurotoxicant an d mechanical injury. Three days after fimbria-fornix/perforant path le sions, there was a loss of SNAP-25 immunoreactivity in hippocampal eff erent pathways and in the lesioned entorhinal cortex. By day 12, there was evidence of reinnervation of hippocampal subfields by SNAP-25-imm unopositive commissural afferent fibers. On day 3, immunoblots showed the appearance of SNAP-25a, a developmental isoform produced by altern ative slicing of nine amino acids in exon 5, in lesioned tissues. This isoform declined by day 12 and was not found in contralateral control hippocampas or non-lesioned brain regions. Stannin immunoreactivity w as unchanged, while GAP-43 was prominent on day 12 post-lesion. Glial fibrillary acidic protein immunoreactivity indicated gliosis near the site of pathway transection. In contrast, trimethyltin induced a marke d loss of stannin immunoreactivity in hippocampal neurons seven days a fter injection. Trimethyltin increased glial fibrillary acidic protein straining in the hippocampus and other damaged regions. SNAP-25 immun oreactivity was markedly increased in mossy fibers and other hippocamp al fields seven days following trimethyltin. Immunoblot analysis showe d that only the adult SNAP-25b isoform was expressed after trimethylti n intoxication. These data suggest that SNAP-25 is a useful marker for presynaptic damage. Furthermore, re-expression of developmental isofo rms of SNAP-25a may precede functional reinnervation when the postsyna ptic target remains intact. Copyright (C) 1996 IBRO.