Kainate induces the expression of the DNA damage-inducible gene, GADD45, in the rat brain

Abstract

The expression of the novel growth arrest and DNA damage-inducible gene GADD45 was examined in kainate-induced epileptic brain damage in the rat using in situ hybridization, northern blot analysis, western blot analysis and immunocytochemistry. Systemic administration of kainate resulted in DNA damage and neuronal degeneration in vulnerable neurons of limbic regions, including the amygdala and hippocampal pyramidal layers, as shown by in situ DNA nick end-labelling and histological staining. GADD45 messenger RNA was transiently increased in non-vulnerable neurons (2–8 h after kainate injection) but was persistently elevated in vulnerable neurons (up to 24 h after injection) after kainate injection. GADD45 protein was elevated in both vulnerable and non-vulnerable neurons at 4 h, but levels decreased in vulnerable neurons thereafter, suggesting that translational blockage of GADD45 protein occurred in these cells. GADD45 protein was overexpressed in non-vulnerable neurons up to 72 h after kainate injection. Because GADD45 may participate in the DNA excision repair process and because it has been shown to be overexpressed in neurons that survive focal cerebral ischaemia, these results support the hypothesis that GADD45 may have a protective role in the injured brain.