Title

Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery.

Document Type

Journal Article

Publication Date

2-19-2020

Journal

Nat Commun

Volume

11

Issue

1

DOI

10.1038/s41467-020-14762-7

Grant Information

CTSI FUNDED

Much of this work was included as part of a dissertation for The George Washington University Institute for Biomedical Sciences (GWU-IBS) Ph.D. training program. We thank GWU-IBS committee members Drs. Anne Chiaramello, Anthony-Samuel LaMantia, and Jason Triplett for their input on this project, and for their comments on the data and the manuscript. This work was supported by Award Number U54HD090257, District of Columbia Intellectual and Developmental Disabilities Research Center award (DC-IDDRC) program (V.G.), R37NS109478 (Javits Award; V. G.), F31NS100277 (T.A.F.), F32NS106723 (E.Z.G.), and 5R01NS099461 (J.S.). Microscopic analysis was carried out at the Children’s Research Institute (CRI) Cell and Tissue Microscopy Core, which is supported by DC-IDDRC grant U54HD090257 (NICHD). We also acknowledge the support of the CRI Bioinformatics Unit, a partnership between the Children’s Research Institute, the Center for Genetic Medicine Research, the Clinical Translational Science Institute at Children’s National (CTSI-CN) and the District of Columbia Intellectual and Developmental Disabilities Research Center (DC-IDDRC). The CTSI-CN is supported through the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, grant UL1TR001876 and KL2TR001877. The CTSA program is led by the NIH’s National Center for Advancing Translational Sciences (NCATS). The DC-IDDRC is supported through the National Institutes of Health (NIH) District of Columbia Intellectual and Developmental Disabilities Research Center Award (DC-IDDRC) program, grant (1U54HD090257). The DC-IDDRC program is led by NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Abstract

Hypoxic damage to the developing brain due to preterm birth causes many anatomical changes, including damage to the periventricular white matter. This results in the loss of glial cells, significant disruptions in myelination, and thereby cognitive and behavioral disabilities seen throughout life. Encouragingly, these neurological morbidities can be improved by environmental factors; however, the underlying cellular mechanisms remain unknown. We found that early and continuous environmental enrichment selectively enhances endogenous repair of the developing white matter by promoting oligodendroglial maturation, myelination, and functional recovery after perinatal brain injury. These effects require increased exposure to socialization, physical activity, and cognitive enhancement of surroundings-a complete enriched environment. Using RNA-sequencing, we identified oligodendroglial-specific responses to hypoxic brain injury, and uncovered molecular mechanisms involved in enrichment-induced recovery. Together, these results indicate that myelin plasticity induced by modulation of the neonatal environment can be targeted as a therapeutic strategy for preterm birth.

Comments

This is an open access PubMed Central article.

Peer Reviewed

1

Open Access

1

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