Vitamin B1 and B12 mitigates neuron apoptosis in cerebral palsy by augmenting BDNF expression through MALAT1/miR-1 axis

Cell Cycle. 2019 Nov;18(21):2849-2859. doi: 10.1080/15384101.2019.1638190. Epub 2019 Sep 10.

Abstract

Through the roles of vitamin B1 and B12 in neuroprotection and in improving cerebral palsy symptoms have been previously noticed, the action mechanism is still unclear. This study aims to investigate the protective effect of vitamin B1 and B12 on neuron injury in cerebral palsy and to clarify the mechanism of vitamin B1 and B12 inhibiting neurons apoptosis, and to focus on the role of lncRNA MALAT1 in this process. In order to investigate the effect of vitamin B1 and B12 on neurons injury in vivo and on neuron apoptosis in vitro, we, respectively, introduced vitamin B1 and B12 into cerebral palsy rat and in apoptosis-induced N2A neurons by Oxygen Glucose Deprivation/reoxygenation (OGD/R). Our results demonstrated that vitamin B1 and B12 treatment improved the motor and memory functions and ameliorated the neurons injury in cerebral palsy rats. OGD/R treatment repressed the expression of MALAT1 and BDNF and the phosphorylation of PI3K and Akt, and enhanced the miR-1 expression, which were all reversed by vitamin B1 and B12 treatment in N2A neurons. Vitamin B1 and B12 inhibited miR-1 expression through MALAT1, promoted BDNF expression and activated PI3K/Akt signaling through the MALAT1/miR-1 axis. Vitamin B1 and B12 suppressed neuron apoptosis by up-regulating BDNF via MALAT1/miR-1 pathway. MALAT1 interference abolished the neuroprotective effect of vitamin B1 and B12 in cerebral palsy rats. Collectively, vitamin B1 and B12 up-regulates BDNF and its downstream PI3K/Akt signaling through MALAT1/miR-1 axis, thus suppressing neuron apoptosis and mitigating nerve injury in cerebral palsy rats.

Keywords: BDNF; Cerebral palsy; MALAT1; miR-1; vitamin B1 and B12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Line, Tumor
  • Cerebral Palsy / pathology*
  • Disease Models, Animal
  • Male
  • Memory / drug effects
  • Mice
  • MicroRNAs / genetics*
  • Motor Activity / drug effects
  • Neurons / pathology
  • Neuroprotection / drug effects
  • Neuroprotective Agents / pharmacology
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Thiamine / pharmacology*
  • Vitamin B 12 / pharmacology*

Substances

  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • MALAT1 long noncoding RNA, rat
  • MIRN1 microRNA, rat
  • MicroRNAs
  • Neuroprotective Agents
  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Vitamin B 12
  • Thiamine

Grants and funding

This study was supported by the grants from the Key Scientific Research Project of Colleges and Universities in Henan province [Grant No. 14A360016], Zhengzhou Collaborative Innovation Major Project [Grant No. 18XTZX12003], Special Research Project of Traditional Chinese Medicine in Henan Province [Grant No. 2018ZY3013], Henan medical science and technology project [Grant No. 2018020223], Key Technological Research Projects of Henan Science and Technology Department [Grant No. 192102310366], Henan Science and Technology Development Plan Project [Grant No. 172102310170], Key Scientific Research Projects Plan of Henan Higher Education Institutions [Grant No. 17A320007], Key Scientific Research Projects Plan of Henan Higher Education Institutions [Grant No. 16B320026], Key Scientific Research Projects Plan of Henan Higher Education Institutions [Grant No. 14A360016], Research Project on Teaching Reform of Vocational Education in Henan Province [Grant No. ZJC18051].