Myelination

…presenting the AxoMetic in vitro myelination platform for discovery of remyelinating therapies.

…the dogma of the field was that myelination was part of a developmental program that set up the neural circuitry, after which it remained static; however, the past decade of research has begun to reveal that myelin plasticity continues well into adulthood, is modulated in an activity dependent manner, and contributes to skill learning. The first part of our study is

Using a mouse model of Glucose Transporter 1 (Glut1) haploinsufficiency which faithfully replicates the core characteristics of De Vivo disease, a human Glut1 Deficiency Syndrome (Glut1DS), we found an early and pronounced decrease in brain glucose, lactate, and glycogen levels. To elucidate the cellular and molecular mechanisms underlying Glut1DS, we conducted an RNA-sequencing analysis on the somatosensory and motor cerebral cortex of a mouse model for Glut1DS.Our analysis revealed 195 up-regulated and 71 down-regulated genes in Glut1-deficient mice compared to wild type controls. Gene set a

…studies has highlighted that altered myelination could be involved in the pathophysiology of ASD. We have characterized the myelination process during development in the cntnap2-/- mouse model of ASD. We observed that oligodendrocyte differentiation and myelination are transiently impaired during cortical development in cntnap2-/- mice. Thus, we observed a reduction in myelinated fibers, the number of nodes of Ranvier and the proportion of mature oligodendrocytes in somat

…We investigate how the unusual myelination pattern develops. Recently, we showed that the internode length is determined early in development followed – after hearing onset - by an increase in axon diameter, which causes the L/D ratio to decrease. Additionally, we found

…oligodendrocyte (OL) development and myelination in Fragile X syndrome (FXS), a NDD caused by the

…as proliferation, differentiation and myelination. Myelination is an adaptive process that depends on neuronal activity. We recently demonstrated that neuronal activity in vivo enhances remyelination in demyelinated lesions (Ortiz et al., 2019, JCI Insight). Here, we investigate whether calcium singal in oligodendroglia play a role in remyelination and whether beha

…Further axon diameter influences myelination and its dynamic regulation might help fine-tune the timing of signal propagation and thus neural circuit function. Despite its importance, we know surprisingly little about how axons grow to such different diameters in the living nervous system and which mechanisms underlie this diversity. To fully understand how nervous systems are built, functionally mature, and remain healthy, we need to underst

…ripple oscillations, whether and how myelination of the hippocampus contributes remains unresolved. Here, we performed LFP measurements in combination with paired recordings between PV+BCs

Peripheral nerve degeneration (PND) regulated by Schwann cells in a hydrogen sulfide (H2S)-pathway-dependent manner is well known, but the underlying molecular properties of Schwann cells during PND are unclear. We investigated H2S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells as unipotent stem cells by using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencing [RNA-seq]) methods. The multi-omics analyses identified several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxid

…ultimately impairing essential myelination processes. To date, no known effective treatment exists. Considering our recent finding, that inhibiting GPR17 enhances oligodendrocyte progenitor cell (OPC) differentiation and myelination following optic nerve crush, we aimed to investigate the impacts of genetic and pharmacological manipulation in a WMI model.C

Introduction: Maternal immune activation (mIA) is a risk factor for schizophrenia. It is hypothesised that mIA-induced fetal neuroinflammation alters neurodevelopment and predisposes offspring to neuropathology. Using our validated mIA model, exposing pregnant rats to the viral mimetic poly(I:C), we have shown that adult offspring exhibit cognitive deficits comparable to those in schizophrenia, and have genomic methylation changes enriched for oligodendrocyte genes.Aims: Examine the relationship between mIA and altered oligodendrocyte development and how these correspond to the onset of adult

Growth-factor receptor bound protein 10 (GRB10) is a signal adapter protein encoded by an imprinted gene, with roles in growth control, cellular proliferation, and insulin signalling. Grb10 has a unique, tissue-specific imprinted expression; the paternal copy being expressed in the CNS, whereas the maternal copy is expressed in most other adult tissues in the mouse and human. Nevertheless, although it is critical for normal behaviour in the mouse, the role of paternal Grb10 in brain growth has yet to be established. Here we investigate the brain-growth in mice lacking paternal Grb10 (Grb10+/p)

Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the Substantia Nigra and Lewy body formation, resulting in a progressive neurodegenerative disorder with movement defects. The impairment of dopaminergic innervation in PD hinders the two main projection systems from the dorsal striatum (Putamen, Pu, and Caudate Nucleus, CN) from effectively responding to cortical and thalamic signals.A potential role of Oligodendrocytes (OLs) in PD was pointed out by recent works describing GWAS PD variants associated with OLs (Bryois et al, Nat Genet, 2020), PD genes e

The chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease affecting myelin and neural structures of the PNS. In recent studies, propionic acid (PA) showed anti-inflammatory and disease modifying effects in multiple sclerosis patients. Additionally, PA exerted neuroprotective and neuroregenerative effects in PNS in vitro cell cultures of Schwann cells (SC) and dorsal root ganglia (DRG). In this study, we investigate the potential effects of PA on SC derived from rats sciatic nerve. First, SC were treated with IFNγ to induce MHC-II receptor expression, which was measu

…contributes to adaptive myelination. This plasticity of myelin tunes neural circuit function and contributes to healthy cognition. The robust mitogenic effect of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, suggests that dysregulated or “hijacked” mechanisms of myelin

The oligodendrocyte generates CNS myelin, which is essential for normal nervous system function. Thus, investigating the regulatory and signaling mechanisms that control its differentiation and the production of myelin is relevant to our understanding of brain development and of adult pathologies such as multiple sclerosis. We have recently established that the activity of voltage-gated Ca++ channels is crucial for the adequate migration, proliferation and maturation of oligodendrocyte progenitor cells (OPCs). Furthermore, we have found that voltage-gated Ca++ channels that function in synapti

…Myelination of previously unmyelinated axons, and changes in the structure on already-myelinated axons, can have large effects on network function. The heterogeneity of the extent of how axons in the CNS are myelinated offers diverse scope for dynamic myelin changes to fine-tune neural circuits. The traditionally held vi

The microbiota-gut-brain axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of brain development and behaviour during early life, adolescence & ageing. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. Studies in animal models have shown that the development of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of fact

…Myelination of previously unmyelinated axons and changes in the structure on already-myelinated axons can have large effects on the function of neuronal networks. Yet myelination has been mostly studied in relation to its functional and metabolic activity. Myelin modifications are increasingly being implicated as a mechanism for sensory-motor learning and unpublished data f