Epigenetic regulation of oligodendrocyte myelination in developmental disorders and neurodegenerative diseases

Abstract

F1000 Faculty Reviews are written by members of the prestigious . They are F1000 Faculty commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. AbstractOligodendrocytes are the critical cell types giving rise to the myelin nerve sheath enabling efficient nerve transmission in the central nervous system (CNS). Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are maintained throughout life. Deficits in the generation, proliferation, or differentiation of these cells or their maintenance have been linked to neurological disorders ranging from developmental disorders to neurodegenerative diseases and limit repair after CNS injury. Understanding the regulation of these processes is critical for achieving proper myelination during development, preventing disease, or recovering from injury. Many of the key factors underlying these processes are epigenetic regulators that enable the fine tuning or reprogramming of gene expression during development and regeneration in response to changes in the local microenvironment. These include chromatin remodelers, histone-modifying enzymes, covalent modifiers of DNA methylation, and RNA modification-mediated mechanisms. In this review, we will discuss the key components in each of these classes which are responsible for generating and maintaining oligodendrocyte myelination as well as potential targeted approaches to stimulate the regenerative program in developmental disorders and neurodegenerative diseases. F1000Research 2020:105 Last updated: 11 FEB 2020 2. Boddaert N, Zilbovicius M, Philipe A, et al.: MRI findings in 77 children with nonsyndromic autistic disorder. PLoS One. 2009; 4(2): e4415. PubMed Abstract | Publisher Full Text | Free Full Text 3. Casanova MF: Neuropathological and genetic findings in autism: the significance of a putative minicolumnopathy. Neuroscientist. 2006; 12(5): 435-41. PubMed Abstract | Publisher Full Text 4. Deoni SCL, Zinkstok JR, Daly E, et al.: White-matter relaxation time and myelin water fraction differences in young adults with autism. Psychol Med. 2015; 45(4): 795-805. PubMed Abstract | Publisher Full Text 5. Hardan AY, Fung LK, Frazier T, et al.: A proton spectroscopy study of white matter in children with autism. Prog Neuropsychopharmacol Biol Psychiatry. 2016; 66: 48-53. PubMed Abstract | Publisher Full Text | Free Full Text 6. He D, Marie C, Zhao C, et al.: Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination. Nat Neurosci. 2016; 19(5): 678-89. PubMed Abstract | Publisher Full Text | Free Full Text 7. Gregory LC, Gevers EF, Baker J, et al.: Structural pituitary abnormalities associated with CHARGE syndrome. J Clin Endocrinol Metab. 2013; 98(4): E737-43. PubMed Abstract | Publisher Full Text | Free Full Text 8. Popescu BF, Lucchinetti CF: Pathology of demyelinating diseases. Annu Rev Pathol. 2012; 7: 185-217. Pu...

Ultrastructural localization of glutamate delta 1 (GluD1) receptor immunoreactivity in the mouse and monkey striatum

“…Although the role of GluD1 in glia remains unknown, recent findings have shown that GluD1 mRNA is strongly expressed in certain types of glia—specifically in oligodendrocyte precursor cells (OPC), also called NG2+ cells (Larson, Zhang, & Bergles, 2016; Saunders et al, 2018). Although NG2+ cells often differentiate into myelinating oligodendrocytes throughout the brain (Antel et al, 2019; Berry, Wang, & Lu, 2020), this is not their only fate. These cells are also found in regions devoid of myelin, suggesting that they potentially have other functions (Larson et al, 2016).…”

Oligodendroglial Epigenetics, from Lineage Specification to Activity-Dependent Myelination

“…As put forward by this review and others [ 83 , 236 , 237 , 238 ], the epigenome is critical in the regulation of the OL lineage, including DNA methylation, histone modifications, chromatin remodeling, lncRNA, and miRNAs. Further studies analyzing how distinct epigenetic layers might contribute together to produce gene regulation would be essential to more precisely characterize the role of epigenetics on the oligodendroglial cell lineage.…”

“…Furthermore, lower mRNA levels of DNMT1 and DNMT3a and higher levels of BDNF were detected in cortical neurons after depolarization by KCl and a sodium channel agonist [ 235 ]. DNA methylation changes have also been observed in epilepsy, which are characterized by abnormal patterns of neuronal activity, but also following electroconvulsive stimulation in mice [ 236 , 237 ]. Among DNMTs, only DNMT3a was higher after stimulation, making it a candidate for activity-dependent de novo methylation [ 237 ].…”

“…However, methylation changes observed in neurons might not reflect similar changes in glial cells. One study comparing hippocampal neuronal NeuN+ and glial NeuN− sorted cells following kainic acid injection, which elicits epilepsy, showed that there was almost no overlap in differentially methylated CpGs between neurons and non-neuronal cells [ 236 ]. Further investigation will be necessary to determine whether neurons and glial cells share common activity-dependent epigenetic responses.…”

Conditional Loss of BAF (mSWI/SNF) Scaffolding Subunits Affects Specification and Proliferation of Oligodendrocyte Precursors in Developing Mouse Forebrain

“…Therefore, ablation of such chromatin and epigenetic factors is expected to call forth structural and functional impairment in the developing or adult brain. Indeed, the impaired development of OL lineage caused by defective chromatin and epigenetic regulation of the various steps involved, is linked to pathophysiological changes leading to neurodevelopmental and neurodegenerative disorders (Maki et al, 2013;Ohtomo et al, 2018;Lu et al, 2019;Berry et al, 2020;Samudyata et al, 2020). Thus, it is plausible that the reported role of BAF155 and BAF170 in OL development (this study) partly highlights the white matter anomalies associated with documented syndromic and non-syndromic disorders associated with BAF complex dysfunction (Sokpor et al, 2017).…”