Improvement Mechanism Of Food-derived Peptides NP-1 On Alcohol-induced Impairment Of Learning And Memary Through Synaptic Plasticity And ERK Pathway

In recent years,research has shown that heavy drinking can lead to different degree of cognitive impairment,and alcoholic brain injury is also becoming a hotspot for current research,such as Alzheimer's disease and Kosakoff Syndrome.As a product of protein,active peptides have been applied in functional foods.An antioxidant activity peptide NP-1 was prepared in the early stage of the study,and its protective effect on the oxidative damage of PC12 cells was found.The model of alcohol brain injury in rats was established by long-term and chronic drinking,and the intervention was conducted with three different doses of NP-1 in low,medium and high doses.The cognitive ability of rats was evaluated by Morris water maze;the morphology and density of pyramidal cells in CA1 area were observed by H&E staining method.To resolve the improvement mechanism of NP-1 on alcoholic brain injury,the protein expression of BDNF,PSD95,CREB and ERK in alcohol stress and different doses of NP-1 was measured by Western-blot technology.At the genetic level,the gene transcription level of ERK signaling pathway-related proteins was determined by RT-PCR.The results of this study are as follows:1.Chronic alcohol exposure and NP-1 intervention results showed that long-term low dose alcohol intake led to slow weight gain in rats and reduced cognitive ability in rats.NP-1 has a certain intervention effect on the growth of rats caused by alcohol and can repair alcoholic cognitive impairment,in which high dose of NP-1 adminstratinon effectively repaired the damage of alcohol to cognitive ability.2.H&E staining results showed that the long-term chronic alcohol exposure caused the rat hippocampal tissue damage and the number and density of neurons in CA1 area decreased significantly,indicating that long-term chronic alcohol intake induced structure damage to the hippocampus CA1 area.The number of neurons and the density of neurons in high dose NP-1 group were significantly increased(p<0.05),and the nerve cells were rearranged in order.The damage of the hippocampal structure was effectively repaired.3.The contents of four kinds on neurotransmitters in the cerebral cortex of rats were detected by LC-MS method and the results showed that long-term chronic alcohol intake related to cognitive produced obvious inhibitory neurotransmitter content,compared with the control group,acetylcholine and dopamine levels of different gender and age alcohol model group rats were significantly decreased(p<0.05).The contents of 5-HT and GABA in rats were significantly increased(p<0.05)except for the young female rats.The content of acetylcholine and dopamine increased significantly in different NP-1 dosage groups(p<0.05).The contents of 5-HT and GABA in rats were significantly reduced(p<0.05)except for the young female rats.4.The expression levels of BDNF,PSD95,CREB and ERK proteins and gene in the hippocampal tissue were determined by Western-blot and RT-PCR.Results showed that compared with the blank control group,the levels of BDNF,PSD95,CREB and ERK proteins and m RNA transcription level in model group significantly decreased(p<0.05).With intervention of NP-1,the corresponding values were desicrably elvated and the significant enhancement was observed in high dose group,indicating NP-1 has powerful ability to repair the alholic indjure to cognition effiency.