Induction of heat-shock protein-70 messenger RNA and protein following systemic kainate injection in the rat: evidence of protein axonal transport.

Abstract

Induction of heat-shock protein-70 was studied using in situ hybridization and immunohistochemistry in the adult rat at different times following intraperitoneal injection of kainate. Marked expression of heat-shock protein-70 messenger RNA was observed during the first 24 h, followed by residual signal at 48 h. Inducible heat-shock protein-70 protein was found in sensitive areas not subjected to early cell death, including the lateral, dorsal and cingular cortices, lateral amygdala, thalamus and hippocampus at 12, 24 and 48 h after injection. In the hippocampus, inducible heat-shock protein-70 immunoreactivity was contained in the soma and proximal dendritic region of neurons of CA3, hilus and CA1 at 12 h, and within the entire dendritic arbor at 24 h. Heat-shock protein-70 immunoreactivity decreased in the cell bodies at four days, but delicate immunostaining appeared in the dorsal fornix, fimbria, and ventral and dorsal hippocampal commissures, as well as in the strata oriens and radiatum of CA3, and part of the stratum radiatum of CA1. Inducible heat-shock protein-70 immunoreactivity at day 7 was mainly localized in the strata oriens and radiatum of CA1 and CA3, and inner one-third of the molecular layer of the dentate gyrus, in which the ipsilateral and commissural hippocampal pathways terminate. These findings show that, in the hippocampus, inducible heat-shock protein-70 is synthesized in the cytoplasm of neurons and subsequently transported at slow rates (about 2-5 mm/day) through the axons to appropriate terminals in the ipsilateral and contralateral hippocampus. A similar pattern is observed for sensitive neurons (heat-shock protein-70 immunoreactive) in the neocortex and thalamus, and labelling of corticocortical, corticostriatal and intrathalamic (between the dorsal and the reticular nuclei) fibres. Since inducible heat-shock protein-70 keeps native proteins unfolded to prevent abnormal configuration following diverse insults, heat-shock protein-70 is proposed as a marker of transient impaired assembly of native proteins in sensitive neurons and axons following intraperitoneal kainate injection.