title: Lithium and oxidative stress lessons from the MPTP model of Parkinson's disease.
abstract: Lithium has been successfully employed therapeutically for treatment of bipolar depressive illness; however, its mechanism of action is poorly understood. Recently, it has been demonstrated by us that lithium can prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dopaminergic neurotoxicity in mice. From analyzing the pattern of protection in various parameters, we suggest that lithium protects against MPTP-induced depletion of striatal dopamine (DA) by preventing free radical-induced inactivation of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis. Possible neuroprotective effect of lithium against H(2)O(2)-induced cell death was assessed in human neuroblastoma; SH-SY5Y cell line. Pretreatment with LiCl (2mM and 4mM) for 7 days protected against H(2)O(2) neurotoxicity in a dose-dependent manner. However, this protection could not be achieved through short-term incubation with LiCl. In agreement; we found that lithium lacks immediate antioxidant activity using the in vitro lipid peroxidation essay indicating that not acute but chronic treatment with lithium allows cells to deal better with oxidative stress.
authors.affiliation: Eve Topf and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, Israel.
authors.forename: Zaher
authors.initials: Z
authors.lastname: Arraf
authors.forename: Tamar
authors.initials: T
authors.lastname: Amit
authors.forename: Moussa B H
authors.initials: MB
authors.lastname: Youdim
authors.forename: Raymond
authors.initials: R
authors.lastname: Farah
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects*; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*
chemical_list: D018020:Lithium Compounds; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine