Axonal sprouting regulates myelin basic protein gene expression in denervated mouse hippocampus.

Abstract The regulation of oligodendrocytegene expression and myelination in vivo in the normal and injured adult CNS is still poorly understood. We have analyzed the effects of axotomy-induced axonal sproutingand microglial activation, on oligodendrocyte myelin basic protein(MBP) gene expression from 2 to 35 days after transection of the entorhino-hippocampal perforant path axonalprojection. In situ hybridization analysis showed that anterograde axonaland terminal degeneration lead to upregulated oligodendrocyteMBP mRNA expression starting between day 2 and day 4, in (1) the deep part of stratumradiatum of CA3 and the dentate hilus, which display axonal sproutingbut no degenerative changes or microglial activation, and (2) the outer part of the molecular layer of the fascia dentata, and in stratummoleculare of CA3 and stratumlacunosum-moleculare of CA1, areas that display dense anterograde axonaland terminal degeneration, myelin degenerative changes, microglial activation and axotomi-induced axonal sprouting. OligodendrocyteMBP mRNA expression reached maximum in both these areas at day 7. MBP gene transcription remained constant in stratumradiatum, stratumpyramidale and stratumoriens of CA1, areas that were unaffected by perforant pathtransection. These results provide strong evidence that oligodendrocyteMBP gene expression can be regulated by axonal sproutingindependently of microglial activation in the injured adult CNS.