ABSTRACT
Researches have shown that melatonin is neuroprotectant in ischemia/reperfusion-mediated injury. Although melatonin is known as an effective antioxidant, the mechanism of the protection cannot be explained merely by antioxidation. This study was devoted to explore other existing mechanisms by investigating whether melatonin protects ischemia/reperfusion-injured neurons through elevating autophagy, since autophagy has been frequently suggested to play a crucial role in neuron survival. To find it out, an ischemia/reperfusion model in N2a cells was established for examinations. The results showed that autophagy was significantly enhanced in N2a cells treated with melatonin at reperfusion onset following ischemia and greatly promoted cell survival, while autophagy blockage by 3-MA led to the shortened N2a cell survival as assessed by MTT, transmission electron microscopy, and laser confocal scanning microscopy. Besides, the protein levels of LC3II and Beclin1 were remarkably increased in ischemia/reperfusion-injured N2a in the presence of melatonin, whereas the expression of p-PKB, key kinase in PI3K/PKB signaling pathway, showed a decrease when compared with untreated subjects as accessed by immunoblotting. Taken together these data suggest that autophagy is possibly one of the mechanisms underlying neuroprotection of melatonin.
ABSTRACT
Objective To investigate the effects of acupuncture on gene expression profile of neurotrophin and its receptors in cerebral cortex of neonatal rats after cerebral hypoxic-isehemic injury,and to explore the molecu- lar mechanism of acupuncture in treatment of neonatal hypoxic-ischemic encephalopathy.Methods The model of cerebral hypoxic-ischemic injury was established with 10 neonatal Sprague-Dawley(SD)rats,who were subjected to acupuncture once daily for 14 days.The animals were sacrificed on the next day of the last acupuncture and their brain cortex was sampled for examination of gene expression,using GEArray Q series neurotrophin and receptors gene array.Results After 14 days of acupuncture,it was found that 48 genes(50% of total genes on the microarray) were expressed differently between the two groups,of which 40 genes(83.3% of differently expressed genes),such as those of the brain-derived neurotrophic factor(BDNF),ciliary neurotrophic factor(CNTF),ciliary neurotrophic factor receptor(CNTFR),basic fibroblast growth factor(bFGF)and fibroblast growth factor receptor type 1 (FGFR1)were up-regulated,and 8 genes(16.7% of differently expressed genes),such as genes of neuregulin-1 (Nrg1),neuregulin-4(Nrg4)and tyrosine kinase C(TrkC)were down-regulated.Conclusion Acupuncture can regulate the expression of various genes of neurotrophin and receptors in cerebral cortex of neonatal rats after cerebral hypoxic-ischemic injury,which might be the mechanism of acupuncture facilitating the recovery of the rats from hy- poxic-ischemic encephalopathy.