Inhibition of microRNA-210 provides neuroprotection in hypoxic-ischemic brain injury in neonatal rats

Authors

Qingyi Ma, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.Follow
Chiranjib Dasgupta, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.Follow
Yong Li, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.Follow
Nikita M. Bajwa, Department of Psychology, Loma Linda University, Loma Linda, CA, USA.
Fuxia Xiong, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Benjamin Harding, Department of Neonatology, Loma Linda University Children's Hospital, Loma Linda, CA, USA.Follow
Richard Hartman, Department of Psychology, Loma Linda University, Loma Linda, CA, USA.Follow
Lubo Zhang, Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.Follow

Document Type

Article

Publication Date

5-1-2016

Publication Title

Neurobiology of disease

E-ISSN

1095-953X

Abstract

Perinatal hypoxic-ischemic encephalopathy (HIE) is associated with high neonatal mortality and severe long-term neurologic morbidity. Yet the mechanisms of brain injury in infants with HIE remain largely elusive. The present study determined a novel mechanism of microRNA-210 (miR-210) in silencing endogenous neuroprotection and increasing hypoxic-ischemic brain injury in neonatal rats. The study further revealed a potential therapeutic effect of miR-210 inhibition using complementary locked nucleic acid oligonucleotides (miR-210-LNA) in 10-day-old neonatal rats in the Rice-Vannucci model. The underlying mechanisms were investigated with intracerebroventricular injection (i.c.v) of miR-210 mimic, miR-210-LNA, glucocorticoid receptor (GR) agonist and antagonist. Luciferase reporter gene assay was conducted for identification of miR-210 targeting GR 3'untranslated region. The results showed that the HI treatment significantly increased miR-210 levels in the brain, and miR-210 mimic significantly decreased GR protein abundance and exacerbated HI brain injury in the pups. MiR-210-LNA administration via i.c.v. 4h after the HI insult significantly decreased brain miR-210 levels, increased GR protein abundance, reduced HI-induced neuronal death and brain infarct size, and improved long-term neurological function recovery. Of importance, the intranasal delivery of miR-210-LNA 4h after the HI insult produced similar effects in decreasing HI-induced neonatal brain injury and improving neurological function later in life. Altogether, the present study provides evidence of a novel mechanism of miR-210 in a neonatal HI brain injury model, and suggests a potential therapeutic approach of miR-210 inhibition in the treatment of neonatal HIE.

Volume

89

First Page

202

Last Page

12

DOI

10.1016/j.nbd.2016.02.011

PubMed ID

26875527

Recommended Citation

Ma, Qingyi; Dasgupta, Chiranjib; Li, Yong; Bajwa, Nikita M.; Xiong, Fuxia; Harding, Benjamin; Hartman, Richard; and Zhang, Lubo, "Inhibition of microRNA-210 provides neuroprotection in hypoxic-ischemic brain injury in neonatal rats" (2016). Loma Linda University Faculty Publications. 339.
https://scholarsrepository.llu.edu/fac_pubs/339