Increases in protein-precursor incorporation in the denervated neuropil of the dentate gyrus during reinnervation

Abstract

Cellular metabolic events accompanying postlesion synaptogenesis in the hippocampus were studied by analyzing incorporation of protein precursor ([ 3H]leucine) in the dentate gyrus. Adult rats were injected intravenously with [ 3H]leucine at periods from 2 to 60 days following unilateral destruction of the entorhinal cortex, and were killed 30 min later. Precursor incorporation was quantified autoradiographically by counting silver grains over the cell bodies and dendrites of dentate granule cells ipsiand contralateral to the lesion. The relative grain density was increased over the denervated portion of the neuropil at 6–12 days postlesion, corresponding to the early phase of terminal proliferation and reactive synaptogenesis. Whereas incorporation was increased over the denervated neuropil, the availability of [ 3H]leucine was decreased relative to the contralateral side in autoradiographic preparations designed to reveal the concentration of the unincorporated 3H-labeled precursor and its diffusible degradation products. Silver grains were not selectively associated with glial cell bodies or vascular elements, but rather were distributed diffusely throughout the neuropil. Increases in grain density over the denervated zone were observed when animals were killed 8 min after the leucine injection, suggesting that the increases were not due solely to rapid transport from granule cell bodies to dendrites. We propose that an increased incorporation of protein precursor occurs primarily within the denervated dendrites of granule cells during the early phase of reinnervation, and that protein synthetic activity in these cells might be involved in the process of reinnervation.