Environmental enrichment enhances cav 2.1 channel-mediated presynaptic plasticity in hypoxic–ischemic encephalopathy

Suk Young Song, Soonil Pyo, Sungchul Choi, Hee Sang Oh, Jung Hwa Seo, Ji Hea Yu, Ahreum Baek, Yoon Kyum Shin, Hoo Young Lee, Ja Young Choi, Sung Rae Cho

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O2 hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Cav 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Cav 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Cav 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.

Original languageEnglish
Article number3414
JournalInternational journal of molecular sciences
Volume22
Issue number7
DOIs
Publication statusPublished - 2021 Apr 1

Bibliographical note

Funding Information:
Funding: This study was supported by the INNOPOLIS Jeonbuk Innovation Cluster, Korea Innovation Foundation (2020-JB-RD-0121) to S.-R.C., Hyundai Motor Chung Mong-Koo Foundation to S.P., and National Research Foundation (NRF-5-2017-A0154-00395) to H.Y.L.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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