The Mechanism Of PX On The Proliferation And Differentiation Of Neural Stem Cells In The Xenopus Tectum

Neural stem cells are principal progenitor cells that can proliferate and differentiate into neurons or glial cells to form functional neural circuits during the development of the CNS,which are related to brain development and repair.It is known that xylene and its derivative PX have neurotoxicity to the CNS of animals.However,the mechanism by which PX affects the proliferation and differentiation of neurons and their structure and function remains unclear.When the tadpoles of Xenopus laevis were exposed to 1 m M sublethal concentration of PX,we found that the number of Hu C/D positive neurons,Brd U positive and PCNA positive proliferating cells were decreased,but there was no significant change on the number of SOX2 positive progender cells and BLBP-positive radial glial cells.And we found that the decrease of proliferation and differentiation of neural stem cells was caused by cell apoptosis.In vivo time-lapse images showed that PX caused significant loss of the TDBL and TBTN structure of neurons,and electrophysiological records indicated PX significantly reduced the number of action potentials and visual stimulus-induced e CSCs.Further examination of synaptic vesicle proteins and postsynaptic receptors revealed that there was no change in the expression levels of Rab3 a and SNAP25 in the optic tectum,while the expression levels of Glu A1 and Glu A2 significantly decreased,suggesting that PX may have specific effects on postsynaptic sites.In addition,the level of cell acetylation in the optic tectum increased after exposure to PX.In order to explore whether PX produces cytotoxicity through transcriptional regulation,we treat tadpoles with TSA and found that the number of apoptotic cells increased significantly.Notably,co-incubation with PX and GA can reduce cell apoptosis and alleviate the structural and functional defects of neurons caused by exposure to PX alone.Moreover,GA and TSA co-incubation tadpoles can also play a saving role.Our results indicate that the transcriptional regulation of PX reduces the proliferation and differentiation of neural stem cells and induced apoptosis in the optic tectum.And PX affects both the morphology and function of neurons.GA is an effective drug for the treatment of PX-induced neurotoxicity and can maintain the balance of transcriptional regulation.These findings lay a foundation for further research on the toxic mechanism of PX on nerve cells during brain formation and repair.