1. Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury
- Author
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Jigao Zhu, Liangwei Yin, Tao Chen, Haiying Chu, Li Kong, Yuzi Wang, Yu Wu, and Haiying Ma
- Subjects
Male ,0301 basic medicine ,MAPK/ERK pathway ,MAP Kinase Signaling System ,NF-E2-Related Factor 2 ,Synaptogenesis ,Tropomyosin receptor kinase B ,Biology ,Biochemistry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Thioredoxins ,0302 clinical medicine ,Neural Stem Cells ,Neurotrophic factors ,Brain Injuries, Traumatic ,Animals ,Rats, Wistar ,Embryonic Stem Cells ,Mitogen-Activated Protein Kinase Kinases ,Brain-derived neurotrophic factor ,Brain-Derived Neurotrophic Factor ,General Medicine ,Neural stem cell ,Rats ,Cell biology ,Transplantation ,Disease Models, Animal ,030104 developmental biology ,nervous system ,Synapses ,Signal transduction ,Neuroscience ,030217 neurology & neurosurgery ,Stem Cell Transplantation - Abstract
Brain-derived neurotrophic factor (BDNF) plays an important role in promoting the growth, differentiation, survival and synaptic stability of neurons. Presently, the transplantation of neural stem cells (NSCs) is known to induce neural repair to some extent after injury or disease. In this study, to investigate whether NSCs genetically modified to encode the BDNF gene (BDNF/NSCs) would further enhance synaptogenesis, BDNF/NSCs or naive NSCs were directly engrafted into lesions in a rat model of traumatic brain injury (TBI). Immunohistochemistry, western blotting and RT-PCR were performed to detect synaptic proteins, BDNF-TrkB and its downstream signaling pathways, at 1, 2, 3 or 4 weeks after transplantation. Our results showed that BDNF significantly increased the expression levels of the TrkB receptor gene and the phosphorylation of the TrkB protein in the lesions. The expression levels of Ras, phosphorylated Erk1/2 and postsynaptic density protein-95 were elevated in the BDNF/NSCs-transplanted groups compared with those in the NSCs-transplanted groups throughout the experimental period. Moreover, the nuclear factor (erythroid-derived 2)-like 2/Thioredoxin (Nrf2/Trx) axis, which is a specific therapeutic target for the treatment of injury or cell death, was upregulated by BDNF overexpression. Therefore, we determined that the increased synaptic proteins level implicated in synaptogenesis might be associated with the activation of the MAPK/Erk1/2 signaling pathway and the upregulation of the antioxidant agent Trx modified by BDNF-TrkB following the BDNF/NSCs transplantation after TBI.
- Published
- 2017