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  • Title: Lysophosphatidylcholine decreases locomotor activities and dopamine turnover rate in rats.
    Author: Lee ES, Soliman KF, Charlton CG.
    Journal: Neurotoxicology; 2005 Jan; 26(1):27-38. PubMed ID: 15527871.
    Abstract:
    Lysophosphatidylcholine (lyso-PTC), a secondary product of S-adenosylmethionine (SAM)-dependent phosphatidylethanolamine (PTE) methylation, is a potent cytotoxin and might be involved in the pathogenesis of Parkinson's disease (PD). Our previous studies showed that the injection of SAM into the brain caused PD-like changes in rodents. Moreover, 1-methyl-4-phenylpyridinium (MPP+), a Parkinsonism-inducing agent, increased lyso-PTC formation via the stimulation of PTE methylation pathway. These results indicate a possible role of lyso-PTC in the PD-like changes seen following the injection of SAM or MPP+. In the present study, lyso-PTC was injected into the lateral ventricle of rats and locomotor activities and the biogenic amine levels were measured to evaluate the effects of lyso-PTC on the dopaminergic system. Quinacrine, a phospholipase A2 (PLA2) inhibitor, was employed to determine its protective effect on SAM-induced PD-like changes by the inhibition of lyso-PTC formation. The results showed that 1 h after the injection, 0.4 and 0.8 micromol of lyso-PTC increased striatal dopamine (DA) by 20 and 24%, decreased 3,4-dihydroxyphenylacetic acid (DOPAC) by 37 and 45% and decreased homovanilic acid (HVA) by 24 and 13%, respectively. Consequently, dopamine turnover rate, (DOPAC + HVA)/DA, was significantly reduced by 44 and 48% in the rat striatum. Meanwhile, the administration of 0.4 or 0.8 micromol of lyso-PTC decreased movement time by 52 and 63%, total distance by 44 and 48% and the number of movements by 43 and 64%, respectively. Quinacrine attenuated SAM-induced hypokinesia without affecting SAM metabolism prior to its action on rat brain. The results obtained indicate that the hypokinesia observed following the administration of lyso-PTC might be related to the decline in DA turnover in the striatum in response to lyso-PTC exposure. The present study suggests that inhibitory effects of lyso-PTC on dopaminergic neurotransmission is one of the contributing factors in SAM and MPP+-induced PD-like changes.
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