Role Of Telomere-regulated Hippocampal Neuron Regeneration In Benzopyrene-induced Learning And Memory Impairment

Objective:Benzo [a] pyrene is one of the common environmental pollutants in polycyclic aromatic hydrocarbons.It mainly comes from incomplete combustion of minerals and is widely present in the environment.It is one of the carcinogens recognized by the World Health Organization,and its carcinogenicity has been widely studied.In recent years,research has found that benzopyrene is also neurotoxic and can cause learning and memory impairment by accelerating brain aging.Studies have shown that reduced hippocampal neuron regeneration is one of the mechanisms of learning and memory impairment related to brain aging.DNA damage can inhibit hippocampal neuron regeneration,and DNA damage is often accompanied by abnormal telomere function.The process of benzo [a] pyrene exposure leading to the impairment of learning and memory function involves complex signal pathways.In this subject,benzo [a] pyrene was used to interfere with C57 mice to observe its behavioral changes and related proteins and genes.Possible intervention targets in the process of learning and memory impairment caused by benzo [a] pyrene provide a scientific basis for preventing and treating neurotoxicity of benzo [a] pyrene.Methods:1.Using different concentrations of benzo [a] pyrene in C57 mice at different times,the Morris water maze test was used to test the learning and memory ability of the mice.2.Enzyme-linked immunosorbent assay to detect B[a]P-7,8-dihydrodiol-9,10-epo xide-DNA adduct(BPDE-DNA)in mouse blood.3.The relative telomere length of mice was detected by real-time quantitative PCR experiments.4.Western blot experiments were performed to detect the expression of p53,p21 and ID1 related signaling pathway molecules in the hippocampus of mice and the expression levels of neural cell surface markers Nestin,?III-tubulin and GFAP.5.Using GraphPad Prism 8.0 for data analysis and processing.The Morris water maze data does not obey the normal distribution.After repeated logarithmic transformation,analysis of variance was repeated.Mean ± standard deviation(?x±s)represents the experimental results.Univariate analysis of variance was used for comparison between groups.A comparison between the two groups was performed,with a test level of ? = 0.05.Results:1.The mice in the exposure group showed significant impairment of learning and memory function: Morris water maze experiment showed that with the increase of benzo [a] pyrene dose and the time of exposure,the escape latency of mice increased significantly,and in the navigation experiment,the number of crossings in the platform has been significantly reduced.2.The content of BPDE-DNA adducts in the blood of the mice in the exposure group was positively correlated with the dose and time of exposure.3.Benzo [a] pyrene exposure can cause shortening of telomere length in mice: realtime fluorescent quantitative PCR results show that the telomere length of mice does not decrease significantly after 1 month of exposure.With the increase of exposure time and dose,the telomere length decreased significantly.4.Benzo [a] pyrene poisoning can activate the p53-p21 signaling pathway and inhibit the expression of ID1,a downstream signaling molecule of p53.The results of western blot showed that under low dose and short-term exposure of benzo [a] pyrene,the expressions of p53,p21 and ID1 did not increase or decrease significantly.With the increase of time and dose,p53 and p21 expressions increased significantly.While ID1 expression is reduced.5.Effects of benzo [a] pyrene exposure on hippocampal neurons: The expression of neural stem cell marker nestin and glial cell marker GFAP increased significantly after exposure;neuronal marker ?-tubulin was at low dose for a short time.No significant change was observed under benzo [a] pyrene exposure,with the increase of exposure time and dose,?-tubulin expression decreased significantly.Conclusion:1.B [a] P poisoning can cause DNA damage.The length of telomere can reflect the degree of DNA damage and can be used as a biological effect marker of DNA damage.2.Telomere shortening in mice caused by benzo [a] pyrene exposure may be one of the mechanisms of learning and memory impairment.This phenomenon may be related to telomere shortening and activation of p53-related pathways to inhibit hippocampal neuron regeneration.