Neuroprotective Effect And Synaptic Plasticity Regulation Of Melatonin In Alzheimer's Disease Rat Cerebellum Via MAPK/ERK Signaling Pathway

ObjectiveThe main purpose of our study was to determine the protective effect of melatonin on A?1-42-mediated in cerebellar neurotoxicity,and further identify the role of MAPK/ERK 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.MethodsAnimals group: repeated A? oligomers i.c.v.injection indeed could develop the animal models of AD,Experimental animals were divided into four groups:Ctrl(ICV injections with 5?l of saline),AD(ICV injections with 5?l of A?1-42),MT(melatoniintra-peritoneal injection),AD+MT(A?1-42 lateral ventricle injection combined with melatonin intraperitoneal injection).The pathological changes of rat cerebellar cortex were detected by HE staining;detection of neuroplastic impairment and the protein expression related to MAPK/ERK signal pathway by IHC and Western Blotting in the cerebellum of the rats.Results1.Repeated soluble A?1-42 i.c.v.injection caused decreases in neuronsand synaptic-related proteinsin the cerebellar cortex.2.A?1-42 can increase the phosphorylation level of MAPK/ERK pathway.3.Melatonin can improve A?1-42-mediated neurotoxicity and synaptic plasticity damage in the cerebellar cortex.At the same time,melatonin significantly reduced the phosphorylation level of ERK.Conclusions1.In AD,the cerebellum also has pathological changes:neuronal apoptosis and synaptic dysfunction.2.Melatonin has neuroprotective effects on A?1-42-mediated neuronal apoptosis and synaptic plasticity damage.3.The MAPK/ERK signaling pathway is involved in the protective effect of melatonin on A?1-42-mediated neurotoxicity.