TY - JOUR
T1 - Lithium and oxidative stress lessons from the MPTP model of Parkinson's disease
AU - Arraf, Zaher
AU - Amit, Tamar
AU - Youdim, Moussa B.H.
AU - Farah, Raymond
PY - 2012/5/10
Y1 - 2012/5/10
N2 - 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 2O 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 2O 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.
AB - 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 2O 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 2O 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.
KW - Dopaminergic neurons
KW - Lipid peroxidation
KW - Lithium
KW - MPTP
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84860260905&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2012.03.055
DO - 10.1016/j.neulet.2012.03.055
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C2 - 22480690
AN - SCOPUS:84860260905
SN - 0304-3940
VL - 516
SP - 57
EP - 61
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -
