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Neuron–oligodendroglial interactions in health and malignant disease

Nature Reviews Neuroscience volume 24, pages 733–746 (2023)Cite this article

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Abstract

Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of adaptive change during childhood development and in adulthood. Myelination is a richly dynamic process, with neuronal activity regulating oligodendrocyte precursor cell proliferation, oligodendrogenesis and myelin structural changes in some axonal subtypes and in some regions of the nervous system. This myelin plasticity and consequent changes to conduction velocity and circuit dynamics can powerfully influence neurological functions, including learning and memory. Conversely, disruption of the mechanisms mediating adaptive myelination can contribute to cognitive impairment. The robust effects of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, indicates that dysregulated or ‘hijacked’ mechanisms of myelin plasticity could similarly promote growth in this devastating group of brain cancers. Indeed, neuronal activity promotes the pathogenesis of many forms of glioma in preclinical models through activity-regulated paracrine factors and direct neuron-to-glioma synapses. This synaptic integration of glioma into neural circuits is central to tumour growth and invasion. Thus, not only do neuron–oligodendroglial interactions modulate neural circuit structure and function in the healthy brain, but neuron–glioma interactions also have important roles in the pathogenesis of glial malignancies.

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Fig. 1: Myelin plasticity: evidence and implications from rodent models.
Fig. 2: Neuronal activity-regulated mechanisms of glioma growth.
Fig. 3: Glioma membrane depolarization promotes tumour cell proliferation.
Fig. 4: Neuron–glioma interactions drive glioma pathobiology.

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Acknowledgements

The authors thank M. Filbin for helpful input on Table 1. This work was supported by grants from Cancer Research UK (to M.M.), ChadTough Defeat DIPG (to M.M.), National Institute of Neurological Disorders and Stroke (R01NS092597 to M.M.), National Institutes of Health (NIH) Director’s Pioneer Award (DP1NS111132 to M.M.), National Cancer Institute (P50CA165962, R01CA258384, U19CA264504 to M.M.), Damon Runyon Cancer Research Foundation (to K.R.T.), Stanford Maternal and Child Health Research Institute (to K.R.T.), Gatsby Charitable Foundation (Gatsby Initiative in Brain Development and Psychiatry to M.M.), HHMI Emerging Pathogens Initiative (EPI), Oscar’s Kids Foundation (to M.M.), McKenna Claire Foundation (to M.M.), Virginia and D. K. Ludwig Fund for Cancer Research (to M.M.), Oligo Nation (to M.M.), Waxman Family Research Fund (to M.M.) and Will Irwin Research Fund (to M.M.).

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  1. Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA

    Kathryn R. Taylor & Michelle Monje

  2. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA

    Michelle Monje

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The authors contributed equally to all aspects of the article.

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Correspondence to Michelle Monje.

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M.M. is on the SAB for TippingPoint Biosciences, and her family holds equity in MapLight Therapeutics.

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Nature Reviews Neuroscience thanks William Weiss, who co-reviewed with Ekin Guney; Klaus-Armin Nave; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Taylor, K.R., Monje, M. Neuron–oligodendroglial interactions in health and malignant disease. Nat. Rev. Neurosci. 24, 733–746 (2023). https://doi.org/10.1038/s41583-023-00744-3

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