Axotomy Increases the Expression of Glucose-Regulated Protein 78 kDa in Rat Facial Nucleus

Abstract

Nerve injuries lead to metabolic and morphological changes in the cell bodies of the neurons of origin. Increases in glucose turnover in axotomized facial and hypoglossal motor nuclei have been described. Glucose-regulated protein 78 kDa (GRP78) is implicated in cellular protein folding and subunit assembly and responds to glucose deficiency. We performed Western blot and immunohistochemistry to determine the effect of axotomy on the expression and regulation of GRP78 in the facial nucleus (FN). Facial nerve axotomy caused a larger and longer increase of GRP78 in the ipsilateral FN than in the contralateral FN. In right ipsilateral FN, axotomy resulted in elevation of GRP78 protein levels, first detected at 12 h and which reached significant, maximal induction at 24 h (75±27% increase). GRP78 protein levels decreased at later time points, but remained elevated over sham-operated controls. In contrast, no significant increase in GRP78 concentrations was found in contralateral left FN. Immunocytochemically, positive GRP78 staining was found mainly in the cytoplasm of motoneurons; there was no nuclear staining. Prominent GRP78-immunostaining appeared in axotomized motoneurons at 24 h postaxotomy as compared with the contralateral, unoperated controls. This augmentation was also observed at 4 and 7 days postaxotomy. The possibility that glucose metabolism and GRP78 levels are two parallel events in the injured facial nucleus is discussed.