Two studies were performed this year. In the first study, we used a protease-resistant pentapeptide called DADLE that has been shown by us in the past to induce a hypo-metabolic state in animals and examined if the drug might help attenuate brain damages caused by stroke in rats. Histological examination using triphenyltetrazolium chloride revealed that brains from ischemic animals treated with DADLE exhibited almost completely intact striata. In contrast, brains from ischemic animals that received saline showed significant infarction in the lateral striatum. Analyses of apoptotic cell death revealed a significant increase in the p-53 mRNA expression in the striatum of ischemic animals that received saline, while those that received DADLE exhibited near normal striatal p-53 expression. This protective effect was accompanied by significant increments in protein levels of glial cell line-derived neurotrophic factor in the striatum of DADLE-treated ischemic animals. These results indicate that DADLE protected against necrotic and apoptotic cell death processes associated with ischemia-reperfusion injury. In the second study, DADLE was used to examine if it can increase the survival of CNS neuronal progenitor cell line. DADLE (1 pM, 0.1 nM, or 10 nM) caused a significant growth inhibition on AF5 cells. DADLE did not cause apoptosis as evidenced by negative TUNEL staining. The cell-cycle progression analysis indicated that DADLE (0.1 nM) caused an arrest of AF5 cell cycle progression at the G1 checkpoint. Neuronal marker indicated that DADLE-treated AF5 cells tend to differentiate more when compared to controls. Results demonstrate that DADLE causes cell cycle arrest and differentiation in a CNS neural progenitor cell line and suggest some potential utilization of DADLE in stem cell research.
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