Alzheimer's disease (AD), a progressive degenerative disorder, is characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. It has been shown that melatonin is a potent antioxidant and free radical scavenger. Additionally, melatonin stimulates several antioxidative enzymes and improves mitochondrial energy metabolism. These findings led us to study amyloid precursor protein transgenic mice, ovariectomized rats, and pheochromocytoma and astroglioma cell lines, to observe whether melatonin had any effect on Alzheimer's symptoms or pathological changes. We found that melatonin had many beneficial effects in experimental models of AD, including improvement of cognitive function, anti-oxidative injury, anti-apoptosis, inhibition of β-amyloid (Aβ) deposition and Aβ fiber formation. Several groups have shown that melatonin has an inhibitory effect on tau protein hyperphosphorylation. These actions may potentially slow down or stop the progression of dementia.

PurposeTo investigate the effect of ultra low molecular weight heparin (ULMWH) on glutamate induced apoptosis in rat cortical cells and to explore the possible mechanisms.Materials and MethodsCell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was first analyzed with Hoechst 33258 and then confirmed by DNA fragmentation. The concentration of free intracellular calcium ([Ca2+]i) was determined with fura-2/AM fluorometry. The expression of Bcl-2 family protein and caspase-3 were evaluated with Western blot.ResultsTypical apoptotic morphological change in rat cortical cells treated with 100 µmol/L glutamate for 24 h was detected by Hoechst 33258 staining, which was then confirmed by the DNA ladder of agarose gel electrophoresis. The apoptotic rate of the glutamate treated cells was up to 33.21%, and 24 h of treatment with glutamate increased [Ca2+]i, down-regulated Bcl-2 expression, up-regulated Bax expression, and increased caspase-3 activation in rat cortical cells. Our research demonstrated that ULMWH pretreatment can prevent the glutamate- induced apoptosis, attenuate the increase of [Ca2+]i not only in medium containing Ca2+ but also in Ca2+-free medium, up-regulate the expression of Bcl-2, down-regulate the expression of Bax, and decrease caspase-3 activation.ConclusionULMWH has neuroprotective capacity to antagonize glutamate-induced apoptosis in cortical cells, through decrease of Ca2+ release and modulation of apoptotic processes.