Effects Of Perinatal Exposure To Swainsonine On Neurogenesis Of Hippocampus And Olfactory Bulb In Mice

In mammals,two neurogenic regions that persist in a lifetime:the subgranular zone(SGZ)of the hippocampal dentate gyrus and the subventricular zone(SVZ).One of them,the neurogenesis in SGZ plays a key role in the normal structure and function of hippocampal learning and memory.And neurogenesis of SVZ has an important role in the structure and function of the olfactory bulb.During the process of neurogenesis(including neural stem cells'proliferation,migration,differentiation,and association with other neurons,etc.),any abnormality may have an influence on the function of the nervous system.The locoweeds,the poisonous leguminous plant of Oxytropis and Astragalus,are commonly known as drunk horse grass.Animals will suffer from"locoism"after eating this kind of grass,affecting their growth and development,production performance,and even leading to death.Therefore,locoweeds have become one of grasses causing the most serious disease in the world.Swainsonine(SW)-a major toxic substance from locoweeds-poisonous animals show drowsy,anorexia and weight loss,accompanied by neurological symptoms such as depression and ataxia,and even neurological diseases such as epilepsy.Although the toxicity of SW is chronic and cumulative,its damage to the nervous system is not easy to repair,and may even bring about permanent neurological disorders.In addition,our previous study showed that SW affected the spatial learning and memory in adult mice.Consequently,the important research to explore the impact of SW on the nervous system is an urgent task.Here,we studied effects of SW on the early neurogenesis of dentate gyrus of hippocampus and olfactory bulb in neonatal mice.During the study process,we established two maternal poisoning models with SW exposure,combined with postnatal in vivo electroporation,BrdU labeling,immunofluorescence staining,western blot and microphotographing techniques.Results were as follows:1.During the establishment of the maternal SW-poisoning model,there was no significant change in body weight of the dams,and body weight as well as brain weight of their offspring.2.With SW exposure to dams,we studied effects on the early postnatal development of dentate gyrus of their offspring.Results found SW inhibited the proliferative capacity of neural progenitor cells in dentate gyrus,resulting in the diminish in the number of surviving granular cells,and led to a decrease in the total length and number of branches of granular cells.Moreover,Sholl analysis showed that SW significantly reduced the number of intersections between the dendrites and concentric circles of the granule cells(representing the complexity of the dendrites).In the 8.4 mg/kg SW-treatment group,the number of NeuN~+and Reelin~+cells in the hilus was significantly increased.In addition,western blot showed that SW significantly decreased the expression levels of spinophilin and NeuN protein in hippocampus.As a result,these may bring about effects on the development of hippocampus.3.With SW exposure to dams,we studied effects on the early development of olfactory bulb of their offspring.SW reduced the proliferation of neural stem cells in SVZ and the number of newborn cells in the olfactory bulb,resulting in a significant increase in the number of CR~+and TH~+interneurons,as well as abnormalities in the morphology and polarity of newborn cells in RMS.And the total length,number of branches,and complexity of newborn granular cells were significantly reduced.In summary,SW had a certain degree of influence on the postnatal neonatal neurogenesis of hippocampal dentate gyrus and olfactory bulb.SW could affect the proliferation of neural stem cells,changed the number of interneurons and the complexity of granular cells'dendrites.These results further prove that SW does damage to the nervous system,which may provide a reference for reducing or decreasing the harm of locoweeds(SW)to grassland animal husbandry.