The Toxic Influence Of Paraquat On Neurogenesis In Hippocampus And Cerebral Cortex Of Mouse

Neurogenesis is the progress of neural stem cells（NSCs）gradually moving to functional areas,undergoing plasticity changes,and finally maturing into a specific nerve cell,which includes the proliferation,differentiation,migration,and apoptosis.In rodents and primates,there are two regions of neurogenesis that are recognized,which are the subgranular zone（SGZ）of the dentate gyrus（DG）and the subventricular zone（SVZ）of lateral ventricle（LV）.With the deepening study of adult neurogenesis in hippocampal dentate gyrus,scientists have learned more about the brain function,the mechanism and the therapeutic method of related diseases.Cerebral cortex is the most complex structure in the nervous system.Several processes are involved into this formation,and any problem occurs in it will cause various neurological diseases,such as epilepsy,Huntington’s disease,and hemi-macrocephaly.Paraquat（PQ）(C₁₂H₁₄C_l2N₂)is no-choice herbicide.It has strong toxicity to humans and animals,and can enter the human body through the skin,respiratory tract and digestive tract,causing multiple systemic toxicity reactions.In recent years,the massive use of paraquat has caused people to worry about the chronic toxicity of long-term low-dose exposure and the impact on the ecological environment.A number of epidemiological studies have shown that long-term exposure of paraquat can cause neurological disease,which will to some extent cause Alzheimer’s disease and Parkinson’s disease.The clinical manifestation of Alzheimer’s disease is the loss of memory,so it is presumed that there may be a slight intrinsic connection with adult neurogenesis in the hippocampus.In addition,during the early neurodevelopment,due to the imperfect development of the blood-brain barrier and the low or absent activity of some functional proteins,early development is susceptible to the effects of environmental neurotoxicity,resulting in abnormal neurophysiological functions and incomplete adult central nervous system.However,what role does paraquat plays in adult neurogenesis and neurogenesis in the developing cerebral cortex is still not known.In this study,paraquat was administered at low doses to establish a model of paraquat poisoning in mice at different stages.Through cell culture,Morris water maze test,Western blot,BrdU in vivo injection,in utero electroporation,multiple immunofluorescent staining,and fluorescence microscopy photogrammetry,the toxic effects of paraquat on mouse hippocampus and cortex neurogenesis hace been studied.The main results are as follows:1.Paraquat affects cell proliferation and induces apoptosis in vitro.Using cell culture and immunofluorescence staining,it was found that paraquat treatment inhibited the proliferation of Neuro-2a cells and caused cell death;Annexin V-FITC/PI double staining was used to detect paraquat inducing apoptosis in PC12 cells by flow cytometry.2.In adult mice,paraquat treatment affected adult neurogenesis,spatial learning and memory in vivo.After exposure to adult mice,the number of newborn cells and the cell survival rate in the dentate gyrus of the hippocampus decreased obviously,and the determination of cell fate altered.In the Morris water maze test,the mice in the experimental group took more time to escape from the water,but the number of crossing the hidden platform decreased,which showed that spatial learning and memory are affected by paraquat exposure;3.Exposure to paraquat during pregnancy affects the morphology of cortical neurons,disrupts neuronal migration and generally influenced neurogenesis in offspring.After paraquat treatment,in daughter mice,the proliferation of VZ/SVZ neural stem cells,the rate of cell cycle exit,the progress of neuronal maturation,as well as neuronal migration were all inhibited.Taken together,paraquat not only affects hippocampal neurogenesis,learning and memory in adult mice,but exposure to paraquat during pregnancy also affects cortical neurogenesis and neuronal migration in embryo mice.