Effect Of Lanthanum Chloride On Dendritic Spine And Rac1-PAK Signal Pathway In Hippocampal Neurons Of Offspring Rat

Objective:In recent years,with the wide application of Rare earth elements?REEs?in production and life,more and more REEs enter the human body through the food chain.Due to the characteristics of accumulation and non-metabolism of REEs,The effects and mechanisms of public health have become urgent problems to be solved.Existing research confirms that REEs can damage children's intelligence and negatively affect the neurological behavior of animals.Lanthanum?La?,as a light rare earth element,is widely found in nature.Due to its unique physical and chemical properties,Lanthanum?La?is often used as a representative material for stud ying the neurotoxicity of REEs.In this study,from the aspect of overall animal experiments,various experimental techniques such as neuroethology,molecular biology,pathology,immunohistochemistry,and tissue fluorescent staining were used to induce the effect of LaC l₃ exposure on learning and memory ability of offspring rats was explored from the perspective of changes in the number of dendritic spines in hippocampal neurons induced by the Rac1-PAK signaling pathway regulated by Tiam1 and p250GAP.In order to further elucidate the mechanism of La damage learning and memory,deep research on the mechanism of neurotoxicity of La and even REEs provides new theoretical references and laboratory data.Methods:Thirty-two Wistar rats were used by the Experimental Animal Center of C hina Medical University.The weight range was 230±20 g,and the ratio of male to female was1:1.The experimental animal room temperature was maintained at 17²3°C and the relative humidity was maintained at 45⁵5%.Animal feed was purchased from S henyang Maohua Biotechnology Co.,Ltd.After adapting for one week in an experimental animal room,it was adapted to the environment,and then the female rats were divided into a control group and a low-,medium-,and high-dose LaC l₃-treated group according to the random principle.According to male and female rats 1:1 caged for mating,the next morning observation of rats,if found in vaginal secretions or vaginal secretions were found in sperm microscopic females can be determined to conceive,record the day of pregnancy 0 days.The pregnant female rats were bred individually and the female rats in the control group were treated with distilled water.The low,medium,and high doses of the La group were treated with distilled water containing 0.125%,0.25%,and 0.5%LaC l₃,respectively,and stopped until the end of the lactation period.This establishes an animal model and then measures each index.Morris water maze test was used to determine the spatial learning and memory ability of offspring rats.Glogi-Gox staining was used to observe the number and morphological changes of hippocampal dendritic spines in rat offspring;Real-time PC R,Western blot,immunofluorescence and immunohistochemistry were used to determine the expression of CaMKII,miRN A132,p250GAP,Tiam1,Pard-3,Rac1,PAK,Cortactin,and Arp2/3 gene s and proteins in hippocampal brains of offspring rats.Result:1.Effects of LaC l₃ on Learning and Memory Ability of O ffspring Rats.In the Morris water maze positioning navigation experiment,the escape latency of the offspring rats seeking to reach the underwater platform gradually increased with the increase in the dose of xenon.In the space exploration experiment,compared with the control group,the number of offspring platforms crossing the target quadrant of the offspring rats in the LaC l₃ treated group was significantly decreased,and some offspring rats in the high dose group showed little or no access to the target quadrant.2.Effects of LaC l₃ on dendritic spines in hippocampal neurons of offspring rats.Compared with the control group,the density of dendritic spines in the hippocampal neurons decreased significantly with the increase in the dose of xenon,and showed a certain dose-effect relationship.Among them,the mushroom and stubby type spines were significantly reduced,while the thin and filopodium types did not change significantly.3.Effects of LaC l₃ on Rac1-PAK Signal Pathway Regulated by Tiam1 and p250GAP.With the increase of lanthanum dose,the expression of miRN A132 decreased and the expression level of p250GAP and its target gene increased gradually.The protein and mRNA expressions of CaMK?,Tiam1,Pard-3,Rac1,PAK,Cortactin,Arp2/3 showed a decreasing trend.Conclusions:1.Radon exposure may lead to a decline in learning and memory ability of offspring rats.2.Lanthanum can cause degeneration of dendritic spines in the offsprings of rats,with the dose increased,dendritic spine density was significantly reduced in hippocampus,and memory-related mushroom,stubby type dendritic spines reduced significantly.3.Lanthanum can affect the expression of Tiam1 and p250GAP by changing the expression levels of CaMK?,Pard-3 and miRNA132,leading to the decrease of the expressions of Rac1-PAK and its downstream regulatory proteins Cortactin and Arp2/3,resulting in changes in the morphology of dendritic spines in hippocampal neurons,which in turn affects neuronal dendritic spine plasticity,leading to decreased levels of learning and memory in offspring rats.