Prefrontal cortex NG2 glia undergo a developmental switch in their responsiveness to exercise.

Aerobic exercise is known to influence brain function, e.g., enhancing executive function in both children and adults, with many of these influences being attributed to alterations in neurogenesis and neuronal function. Yet oligodendroglia in adult brains have also been reported to be highly responsive to exercise, including in the prefrontal cortex (PFC), a late myelinating region implicated in working memory. However, whether exercise affects oligodendroglia or myelination in juveniles, either in the PFC or in other brain regions, remains unknown. To address this, both juvenile and young adult mice were provided free access to running wheels for four weeks followed by an analysis of oligodendrocyte development and myelination in the PFC and the corpus callosum, a major white matter tract. Working memory and PFC NG2+ cell development were both affected by exercise in juvenile mice, yet surprisingly these exercise-mediated effects were distinct in juveniles and young adults. In the PFC, NG2+ cell proliferation was increased in exercising juveniles, but not young adults, whereas newly-born oligodendrocyte production was increased in exercising young adults, but not juveniles. Although no overall changes in myelin genes were found, elevated levels of Monocarboxylate Transporter 1, a glial lactate transporter important during active myelination, were found in the PFC of exercising young adults. Overall our findings reveal that long-term exercise modulates PFC glial development and does so differentially in juvenile and young adult mice, providing insight into the cellular responses that may underlie cognitive benefits to teenagers and young adults in response to exercise. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 687-700, 2018.

Distinct Requirements for Extracellular and Intracellular MMP12 in the Development of the Adult V-SVZ Neural Stem Cell Niche.

The regulatory mechanisms that control neural stem cell (NSC) activation in the adult ventricular-subventricular zone (V-SVZ) stem cell niche have been the focus of intense investigation, yet how the niche first develops and organizes is poorly understood. Here, we examined matrix metalloproteinases (MMPs) for potential roles in V-SVZ stem cell niche development. MMP12 was found to promote appropriate niche cellular arrangements, the formation of specialized niche extracellular matrix, and the translational planar cell polarity of ependymal cells that surround and support niche NSCs. Surprisingly, ependymal cells were found to have an intracellular pool of MMP12 that promoted ependymal cell ciliogenesis by upregulating FOXJ1. In addition, both extracellular and intracellular MMP12 were found to regulate V-SVZ niche output by promoting NSC quiescence. These findings reveal that extracellular and intracellular MMP12 have both unique and overlapping roles that help orchestrate the development of the adult V-SVZ stem cell niche.

Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity.

Many behavioral experiences are known to promote hippocampal neurogenesis. In contrast, the ability of behavioral experiences to influence the production of oligodendrocytes and myelin sheath formation remains relatively unknown. However, several recent studies indicate that voluntary exercise and environmental enrichment can positively influence both oligodendrogenesis and myelination, and that, in contrast, social isolation can negatively influence myelination. In this review we summarize studies addressing the influence of behavioral experiences on oligodendrocyte lineage cells and myelin, and highlight potential mechanisms including experience-dependent neuronal activity, metabolites, and stress effectors, as well as both local and systemic secreted factors. Although more study is required to better understand the underlying mechanisms by which behavioral experiences regulate oligodendrocyte lineage cells, this exciting and newly emerging field has already revealed that oligodendrocytes and their progenitors are highly responsive to behavioral experiences and suggest the existence of a complex network of reciprocal interactions among oligodendrocyte lineage development, behavioral experiences, and brain function. Achieving a better understanding of these relationships may have profound implications for human health, and in particular, for our understanding of changes in brain function that occur in response to experiences. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.