Neuroprotective effects of lithium in cultured cells and animal models of diseases

摘要: Lithium, the major drug used to treat manic depressive illness, robustly protects cultured rat brain neurons from glutamate excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors. The lithium neuroprotection against excitotoxiciy is long-lasting, requires long-term pretreatment and occurs at therapeutic concentrations of this drug. neuroprotective mcchanisms involve inactivation NMDA receptors, decreased expression pro-apoptotic proteins, p53 Bax, enhanced cytoprotective protein, Bcl-2, activation cell survival kinase, Akt. In addition, suppresses glutamate-induced loss activities Akt, cyclic AMP-response element binding protein (CREB), c-Jun - N-terminal kinase (JNK) p38 kinase. Lithium also reduces damage in animal models neurodegenerative diseases which has been implicated. model stroke using middle cerebral artery occlusion, markedly neurologic deficits decreases infarct volume even when administered after onset ischemia. a Huntington's disease model, significantly lesions resulting intrastriatal infusion quinolinic acid, an excitotoxin. Our results suggest that might have utility treatment disorders addition its common use for bipolar patients.