Seol Heui Han

Melatonin attenuates kainic acid-induced hippocampal neurodegeneration and oxidative stress through microglial inhibition.

Abstract: The antioxidant and anti‐inflammatory effects of melatonin on kainic acid (KA)‐induced neurodegeneration in the hippocampus were evaluated in vivo. It has been suggested that the pineal secretory product, melatonin, protects neurons in vitro from excitotoxicity mediated by kainate‐sensitive glutamate receptors, and from oxidative stress‐induced DNA damage and apoptosis. In this study, we injected 10 mg/kg kainate intraperitoneally (i.p.) into adult male Sprague‐Dawley rats. This results in selective neuronal degeneration accompanied by intense microglial activation and triggers DNA damage in the hippocampus. We tested the in vivo efficacy of melatonin in preventing KA‐induced neurodegeneration, oxidative stress and neuroinflammation in the hippocampus. Melatonin (2.5 mg/kg, i.p.) was given 20 min before, immediately after, and 1 and 2 hr after KA administration. Rats were killed 72 hr later and their hippocampi were examined for evidence of DNA damage (in situ dUTP end‐labeling, i.e. TUNEL staining), cell viability (hematoxylin and eosin staining), and microglial (isolectin‐B4 histochemistry) and astroglial responses (glial fibrillary acidic protein immunohistochemistry), as well as lipid peroxidation (4‐hydroxynonenal immunohistochemistry). A cumulative dose of 10 mg/kg melatonin attenuates KA‐induced neuronal death, lipid peroxidation, and microglial activation, and reduces the number of DNA breaks. A possible mechanism for melatonin‐mediated neuroprotection involves its antioxidant and anti‐inflammatory actions. The present data suggest that melatonin is potentially useful in the treatment of acute brain pathologies associated with oxidative stress‐induced neuronal damage such as epilepsy, stroke, and traumatic brain injury.

CYP2D6*4 polymorphism is not associated with Parkinson's disease and has no protective role against Alzheimer's disease in the Korean population

Abstract CYP2D6*4 polymorphism is reported to be associated with Parkinsons disease (PD) and to have protective role against Alzheimers disease (AD). Such findings are not extensively studied in the Oriental population, especially Koreans. The effects of CYP2D6*4 polymorphism on AD and PD were investigated by polymerase chain reaction‐restriction fragment length polymorphism in Korean subjects. Heterozygous mutant allele was found in four of 93 patients with PD, 0 of 32 patients with AD and one of 121 control subjects (59 stroke, 59 normal controls and four other psychiatric disorders), but no homozygous mutant allele was found. There were no statistically significant differences between the AD group and controls, and between the PD group and controls. In conclusion, we suggest that CYP2D6*4 polymorphism does not confer susceptibility to PD in the Korean population. Also, due to such a rare occurrence of the CYP2D6*4 polymorphism, we can not confirm the protective role of the polymorphism against AD in the Korean population.