Homocysteine (Hcy), an independent risk factor for
atherosclerosis, undergoes auto-oxidation and generates
reactive oxygen species, which are thought to be main cause of Hcy neurotoxicity. However, the mechanisms leading to
neurodegenerative disorders are poorly understood because studies that have investigated the potential neurotoxicity of
hyperhomocysteinemia in vivo are scarce. The purpose of this study was to test whether daily administration of
methionine, which induces
hyperhomocysteinemia, causes glial hyperactivity, and also to investigate the protective effects of
melatonin on the brain tissue against oxidative stress of Hcy in rats. There was a significant development of oxidative stress as indicated by an increase in
malondialdehyde + 4-hydroxyalkenals in hippocampus and cortex of hyperhomocysteinemic rats, whereas significant reduction was found in the activity of
glutathione peroxidase (GSH-Px). Co-treatment with
melatonin inhibited the elevation of lipid peroxidation and significantly increased GSH-Px activity in the brain regions studied. Western blot analysis revealed an increase in
glial fibrillary acidic protein (GFAP) contents both in hippocampus and frontal cortex (p < 0.001) of hyperhomocysteinemic rats compared to the controls. Administration of
melatonin significantly decreased GFAP contents in hippocampus and cortex (p < 0.05). S100B contents increased only in frontal cortex in hyperhomocysteinemic rats compared to the control (p < 0.01) and was inhibited by
melatonin treatment (p < 0.01). The present findings show that Hcy can sensitize glial cells, a mechanism which might contribute to the pathogenesis of
neurodegenerative disorders, and further suggest that
melatonin can be involved in protecting against the toxicity of Hcy by inhibiting
free radical generation and stabilizing glial cell activity.