Effect Of Developmental Exposure To Decabromodiphenyl Ether On Olfactory And Cortical Neurogenesis Of Mouse Offspring

Neurogenesis is a process of generating functional neurons from neural stem cells,occurs throughout life in restricted brain regions in mammals.Functional integration of newborn neurons in the central nervous system(CNS)is a critical process for the development of CNS.And neurogenesis is prone to be dysregulated in some physiological and pathological conditions.Several developmental neural disorders,such as autism and epilepsy are accompanied by alterations in neurogenesis.These neural disorders affect millions of children all over the world.Industrial chemicals widely distributed in the environment are major contributors to these pandemic developmental disabilities.Decabromodiphenyl ether(BDE-209)is a class of additive brominated flame retardant widely used in many products,including textiles,consumer electronics,plastics,building materials and furnishings.BDE 209 is a kind of persistent organic pollutant and has neurodevelopmental toxicology.It can contaminate environment and food chain and will also pose a threat to human health.The problems it caused have been arousing widespread concern.We firstly established an animal model of BDE 209 developmental exposure.Then we perform BrdU labeling,GFP transfection,primary cortical neuron culture,immunohistochemistry and western blotting to illustrate the neurotoxicity of BDE 209 on cortical and postnatal SVZ neurogenesis in terms of history and morphology.And provide a certain theoretical basis for the establishment of the corresponding national standard.1.By BrdU labeling and double labeling immunohistochemistry,we found that BDE 209exposure disrupted the proliferation of type-B stem cells.Results indicated that more type-B stem cells in the SVZ differentiated into neuroblasts after developmental BDE 209 exposure.2.BDE 209 exposure reduced the number of newborn cells in the GCL and CalR~+interneurons in the GCL and GL of the OB.3.The polarity and directionality of migrating neurons in the rostral migratory stream(RMS)were dramatically disrupted after BDE 209 exposure.But the migrating rate of neuroblasts in the RMS did not change.Indeed,BDE 209 also decreased the dendrite complexity,apical branching points and total dendritic length of newborn granules cells in the OB.4.BDE 209 exposure inhibited neuronal migration in the developmental cerebral cortex.But BDE 209 did not affect the proliferation and differentiation of neural stem cells during cortical neurogenesis.Indeed,we also showed that BDE 209 inhibited axonal growth through primary cortical neuron culture.In summary,our research illustrated that developmental exposure to BDE 209 impaired neurogenesis in olfactory bulb and developmental cortex and might further resulted in some dysfunction of these brain regions.