INCREASED LEVELS OF STATIN, A MARKER OF CELL-CYCLE ARREST, IN RESPONSE TO HIPPOCAMPAL NEURONAL INJURY

Injured neurons in the CNS are known to synthesize high levels of prol iferation related oncogene products and heat shock proteins without di viding. Statin is a cell cycle regulated nuclear phosphoprotein, selec tively associated with the non-proliferative state in a wide variety o f cell types. In the present study, neuronal statin was examined follo wing lethal or sublethal neuronal injuries in the hippocampus of Alzhe imer's disease patients, in rats receiving kainate lesions to the dors al hippocampus and in entorhinal cortex lesioned rats. Immunolabelling of nuclear statin showed that statin immunoreactivity increased prefe rentially in CA1 pyramidal neurons of the hippocampus in Alzheimer's d isease. In kainate lesioned rats, statin immunoreactivity was markedly induced in the CA3 hippocampal region in association with neuronal lo ss. Entorhinal cortex lesioned rats showed a transient induction of st atin between 2 and 6 days post lesion in CA1 neurons. However, cell co unts in entorhinal cortex lesioned rats remained unaltered in the CA1 and granule cell layers during the entire 30 day time course, indicati ng that increased statin levels are not secondary to neuronal degenera tion and are not necessarily accompanied by irreversible neuronal deat h. It is concluded that, in addition to proliferation related gene pro ducts, neuronal injury induces an increase in levels of statin, a nucl ear marker of cell cycle arrest. Furthermore, statin may be a potentia lly useful marker of injurious neuronal stress, even under conditions that do not necessarily lead to irreversible cell death.