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Neuroprotective Role of Exogenous Brain-Derived Neurotrophic Factor in Hypoxia–Hypoglycemia-Induced Hippocampal Neuron Injury via Regulating Trkb/MiR134 Signaling

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Abstract

Hypoxic–ischemic brain injury is an important cause of neonatal mortality and morbidity. Brain-derived neurotrophic factor (BDNF) has been reported to play a neuroprotective role in hypoxic–ischemic brain injury; however, the specific effects and mechanism of BDNF on hypoxic–hypoglycemic hippocampal neuron injury remains unknown. The current study investigated the action of BDNF in regulating cerebral hypoxic-ischemic injury by simulating hippocampal neuron ischemia and hypoxia. We found that BDNF, p-Trkb, and miR-134 expression levels decreased, and that exogenous BDNF increased survival and reduced apoptosis in hypoxic–hypoglycemic hippocampal neurons. The results also show that BDNF inhibits MiR-134 expression by activating the TrkB pathway. Transfection with TrkB siRNA and pre-miR-134 abrogated the neuroprotective role of BDNF in hypoxic–hypoglycemic hippocampal neurons. Our results suggest that exogenous BDNF alleviates hypoxic–ischemic brain injury through the Trkb/MiR-134 pathway. These findings may help to identify a potential therapeutic agent for the treatment of hypoxic–ischemic brain injury.

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Acknowledgements

The project was supported by Natural Science Foundation Research Project of Shaanxi province (2016JM8073).

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Authors and Affiliations

  1. Department of Neurosurgery, Shaanxi Provincial People’s Hospital, NO 256, Youyi West Road, Xi’an, 710068, China

    Weidong Huang, Facai Meng, Jie Cao, Xiaobin Liu, Jie Zhang & Min Li

Authors
  1. Weidong Huang
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  2. Facai Meng
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  3. Jie Cao
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  4. Xiaobin Liu
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  5. Jie Zhang
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  6. Min Li
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Corresponding author

Correspondence to Weidong Huang.

Additional information

Highlights

1. H–H treatment decreased BDNF, p-Trkb, and miR-134 expression

2. Exogenous BDNF significantly increased p-Trkb expression

3. BDNF increased H–H-induced hippocampal neuron growth

4. BDNF inhibits miR-134 expression via activating TrkB

5. TrkB and miR-134 involved in the action of BDNF

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Supplementary Fig. 1

Cocl2 treatment increased the expression of HIF-1α (marker of hypoxia) in hippocampal neurons. HIF-1α protein expression was measured by Western blot. Cells were treated by 300 μM Cocl2 for 3 and 9 h to simulate hypoxia in vitro. Data were repeated at least three times (n=3); *P<0.05 versus control group. (GIF 27 kb)

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Huang, W., Meng, F., Cao, J. et al. Neuroprotective Role of Exogenous Brain-Derived Neurotrophic Factor in Hypoxia–Hypoglycemia-Induced Hippocampal Neuron Injury via Regulating Trkb/MiR134 Signaling. J Mol Neurosci 62, 35–42 (2017). https://doi.org/10.1007/s12031-017-0907-z

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  • DOI: https://doi.org/10.1007/s12031-017-0907-z

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