BDNF promotes neuronal survival after neonatal hypoxic-ischemic encephalopathy by up-regulating Stx1b and suppressing VDAC1

• Published in: Brain research bulletin 2021-09, Vol.174, p.131-140
• Main Authors: Xue, Lu-Lu, Du, Ruo-Lan, Hu, Yue, Xiong, Liu-Lin, Su, Zhang-Yu, Ma, Zheng, Tan, Ya-Xin, Liu, Jia, Hu, Qiao, Zhu, Zhao-Qiong, Liu, Xue-Zheng, Wang, Ting-Hua
• Format: Article
• Language: English
• Subjects: BDNF; Neonatal HIE; Neurite regeneration; Stx1b; VDAC1
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2021.05.013

•HIE exerted tremendous pernicious effects on the development of neonatal brain.•BDNF induces lower expression of Stx1b and higher expression of VDAC1.•BDNF promotes neurite regeneration.•This study provide a theoretical foundation for clinical therapy of HIE. Neonatal hypoxic-ischemic encephalopathy (HIE), is a major cause of neurologic disorders in terms of neonates, with the unclear underlying mechanisms. In the study, triphenyl tetrazolium chloride (TTC) staining and Zea-longa score were performed to examine the neurologic damage in hypoxia and ischemia (HI) rats. The results showed that HI induced obviously infarct and serious neurologic impairment in neonatal rats. Then, protein chip was applied to detect the differential expression genes in cortex and hippocampus and found the brain-derived neurotrophic factor (BDNF) down-regulated both in cortex and hippocampus. Moreover, low expression of BDNF after HI in right cortex and hippocampus was validate by immunohistochemistry (IHC) and Western Blotting (WB). Afterwards, overexpressing and interfering HSV vector were produced, then verified by immunofluorescent staining and real-time quantitative polymerase chain reaction (qRT-PCR). The results of Tuj1 staining indicated that overexpression of BDNF could promote axonal regeneration and inhibit neuron swelling, whereas BDNF interference take an opposite effect after Oxygen glucose deprivation (OGD) injury. Finally, the interaction network among BDNF and associated proteins as examined by Genemania and confirmed by qRT-PCR. We found that the expression of VDAC1 was decreased and Stx1b was increased when BDNF overexpressing, which indicated that BDNF promoted neurite regrowth after OGD might be related to downregulation of VDAC1 and upregulation of Stx1b. Our results might provide novel strategy for the treatment of neurological defects induced by cerebral ischemia and hypoxia.