Neuronal Protective Effect Of Melatonin On Aβ_1-42-Mediated Neurodegeneration Via Reelin Signaling Pathway

Objectives The main purpose of our study was to determine the effect of melatonin on Aβ1-42-mediated neurodegeneration, and further identify the role of Reelin signaling pathway in the neuroprotective effect of melatonin. Our results will provide a theoretical basis for further study melatonin for the prevention and treatment of aging and age-related neurodegenerative diseases.Methods Experimental animals were divided into four groups: control(ICV injections with 5μl of saline), Aβ1-42(ICV injections with 5μl of Aβ1-42), melatonin(i.p. injection with melatonin) and Aβ1-42 with melatonin groups. The expression level of neural plasticity-related proteins, glial fibrillary acidic protein(GFAP) and Reelin protein in cerebral cortex was examined by immuno-histochemistry and Western Blotting method. The gene expression level of Reelin in cerebral cortex was determined by q PCR. Primary cortical neuron culture was condcted by using embryonic day 18 rats. The cells were divided into four treatment groups: control, Aβ1-42, melatonin, Aβ1-42 with melatonin treatment groups. Synaptic maker proteins were detected by immunohistochemical staining, the expression of Reelin and its adaptor protein p Dab1 were detected by western blotting analysis.Results1、Aβ1-42 could change the synaptic plasticity, activate astrocytes, and decrease the gene and protein expression levels of reelin in cerebral cortex. 2、Melatonin could partially ameliorate the effect of Aβ1-42 on synaptic plasticity, astrocytes activation and Reelin. 3 、 Using primary cultured cortical neurons, we further confirmed that melatonin could ameliorate the effect of Aβ1-42 on synaptic plasticity, astrocytes activation, Reelin and p Dab1Conclusions Melatonin has a neuroprotective effect on Aβ1-42-mediated neurodegeneration.Melatonin may play a neuroprotective role in Aβ1-42-mediated neurodegeneration through Reelin signaling pathway.