Institute of Biomedical Sciences

Title

Environmental Enrichment Promotes Oligodendrocyte Maturation and Improves Functional Recovery in a Mouse Model of Preterm Birth

Poster Number

23

Document Type

Poster

Keywords

Preterm Birth, Brain Injury, Hypoxia, White Matter, Oligodendrocytes, Environmental Enrichment

Publication Date

4-2017

Abstract

Hypoxic damage to the developing brain sustained as a consequence of preterm birth is associated with permanent neurodevelopmental disabilities. This oxygenation failure predisposes preterm infants to white matter (WM) injury and is associated with many anatomical changes, the most distinctive of which is damage to the periventricular WM. This diffuse WM injury results in the loss of glial cells and causes a significant disruption in myelination, which leads to cognitive and behavioral impairments throughout childhood. However, the mechanisms underlying glia susceptibility and altered WM development as well as the potential for functional recovery from hypoxic injury are not fully understood. Here, we focus on utilization of an enriched environment to attenuate the effects of perinatal hypoxia (HX) on WM development.

Environmental enrichment (EE) is a noninvasive combination of social and physical enhancement of surroundings that provides mammals with more complex social interactions, exposure to novel stimuli, and an opportunity for voluntary physical activity. Previous studies demonstrated that the environment affects both neural plasticity and functional recovery after brain injury. Furthermore, social, family, and environmental factors contribute to improved cognitive outcome of premature children. Therefore, the environment plays a crucial role in promoting functional recovery in the CNS, and may play a role in the repair of developing WM after HX injury.

Data obtained using an established rodent model demonstrate that EE ameliorates the effects of perinatal HX and enhances oligodendrocyte regeneration after injury. Further, EE improved performance on a WM-specific behavioral task. Interestingly, EE did not have a WM effect on mice maintained under normal physiological conditions, but did induce hippocampal neurogenesis in a set of normoxic control experiments. This project will test the hypothesis that the resultant oligodendrogenesis and behavioral improvement seen following HX and subsequent EE will lead to enhanced myelination. Control experiments will be performed to determine the relative individual contributions of locomotor activity and increased socialization. Also, we will investigate alternate paradigms of EE to determine whether critical periods of exposure and recovery exist.

While considerable progress has been made in identifying and modulating the mechanisms involved in premature brain injury, additional research is needed. The proposed study will not only shed light on the cellular and molecular mechanisms of WM injury, but will also aid in the development of new therapeutic approaches for enhancing recovery after early postnatal hypoxic injury during critical periods of neurodevelopment.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

1

Comments

To be presented at GW Annual Research Days 2017.

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Environmental Enrichment Promotes Oligodendrocyte Maturation and Improves Functional Recovery in a Mouse Model of Preterm Birth

Hypoxic damage to the developing brain sustained as a consequence of preterm birth is associated with permanent neurodevelopmental disabilities. This oxygenation failure predisposes preterm infants to white matter (WM) injury and is associated with many anatomical changes, the most distinctive of which is damage to the periventricular WM. This diffuse WM injury results in the loss of glial cells and causes a significant disruption in myelination, which leads to cognitive and behavioral impairments throughout childhood. However, the mechanisms underlying glia susceptibility and altered WM development as well as the potential for functional recovery from hypoxic injury are not fully understood. Here, we focus on utilization of an enriched environment to attenuate the effects of perinatal hypoxia (HX) on WM development.

Environmental enrichment (EE) is a noninvasive combination of social and physical enhancement of surroundings that provides mammals with more complex social interactions, exposure to novel stimuli, and an opportunity for voluntary physical activity. Previous studies demonstrated that the environment affects both neural plasticity and functional recovery after brain injury. Furthermore, social, family, and environmental factors contribute to improved cognitive outcome of premature children. Therefore, the environment plays a crucial role in promoting functional recovery in the CNS, and may play a role in the repair of developing WM after HX injury.

Data obtained using an established rodent model demonstrate that EE ameliorates the effects of perinatal HX and enhances oligodendrocyte regeneration after injury. Further, EE improved performance on a WM-specific behavioral task. Interestingly, EE did not have a WM effect on mice maintained under normal physiological conditions, but did induce hippocampal neurogenesis in a set of normoxic control experiments. This project will test the hypothesis that the resultant oligodendrogenesis and behavioral improvement seen following HX and subsequent EE will lead to enhanced myelination. Control experiments will be performed to determine the relative individual contributions of locomotor activity and increased socialization. Also, we will investigate alternate paradigms of EE to determine whether critical periods of exposure and recovery exist.

While considerable progress has been made in identifying and modulating the mechanisms involved in premature brain injury, additional research is needed. The proposed study will not only shed light on the cellular and molecular mechanisms of WM injury, but will also aid in the development of new therapeutic approaches for enhancing recovery after early postnatal hypoxic injury during critical periods of neurodevelopment.