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 proliferation related oncogene products and heat shock proteins without dividing. Statin is a cell cycle regulated nuclear phosphoprotein, selectively associated with the non-proliferative state in a wide variety of cell types. In the present study, neuronal statin was examined following lethal or sublethal neuronal injuries in the hippocampus of Alzheimer's disease patients, in rats receiving kainate lesions to the dorsal hippocampus and in entorhinal cortex lesioned rats. Immunolabelling of nuclear statin showed that statin immunoreactivity increased preferentially in CA1 pyramidal neurons of the hippocampus in Alzheimer's disease. In kainate lesioned rats, statin immunoreactivity was markedly induced in the CA3 hippocampal region in association with neuronal loss. Entorhinal cortex lesioned rats showed a transient induction of statin between 2 and 6 days post lesion in CA1 neurons. However, cell counts in entorhinal cortex lesioned rats remained unaltered in the CA1 and granule cell layers during the entire 30 day time course, indicating that increased statin levels are not secondary to neuronal degeneration and are not necessarily accompanied by irreversible neuronal death. It is concluded that, in addition to proliferation related gene products, neuronal injury induces an increase in levels of statin, a nuclear marker of cell cycle arrest. Furthermore, statin may be a potentially useful marker of injurious neuronal stress, even under conditions that do not necessarily lead to irreversible cell death.