Abstract

Li+ exerts protective effect against several neurotoxins in neuronal cell preparations. Here we examined the antiapoptotic effects of GSK3 beta in cerebellar granule neurons (CGNs) in the presence of several neurotoxins. Acute treatment with Li+ protected neurons against nocodazole and serum/potassium (S/K) deprivation, but were ineffective against kainic acid and MPP+. Li+ 5mM also decreased caspase-3 activation induced by nocodazole and S/K deprivation as measured by Ac-DEVD-p-nitroaniline and the breakdown of alpha-spectrin. All the neurotoxins used in the present study activated GSK3 beta, evaluated with a specific antibody phospho-GSK-3 beta (Ser9) by Western-blot and immunocytochemistry and were always inhibited by Li+ 5mM. Our results implicate Li+ in the regulation of apoptosis mediated by caspase activation (Type I). Furthermore inhibition of GSK3 beta by acute treatment with Li+ 5mM is not an indicator of neuroprotection. The acute antiapoptotic function of Li+ is discussed in terms of its inhibition of Type I pathway, the intrinsic (mitochondrial) apoptotic pathway in cerebellar granule cells.