ArticleAnnals of clinical and translational neurology2015
Hypomyelination following deletion of Tsc2 in oligodendrocyte precursors.
Article in Annals of clinical and translational neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- White matter abnormalities in tuberous sclerosis complex: a systematic review of diffusion tensor imaging studies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Longitudinal Effects of Everolimus on White Matter Diffusion in Tuberous Sclerosis Complex.Pediatric neurology · 2019Trial
- Effects of Anesthesia Neurotoxicity on Oligodendrocyte Development and Myelination: An In Vitro Study Using Primary Cultures.International journal of molecular sciences · 2026Article
- Myelin dysfunction in autism spectrum disorder: insights into core symptoms and mechanisms of brain development.Molecular psychiatry · 2026Review
- ENT1 inhibitor J4 restores cognitive function and white-matter integrity in a mouse model of tuberous sclerosis complex.Journal of biomedical science · 2026Article
- Molecular and biochemical correlates of frontal lobe white matter degeneration in humans with alcohol use disorder.Advances in drug and alcohol research · 2026Article
- Cell-cell communication dysregulation in tuberous sclerosis complex cortical tubers and focal cortical dysplasia.Acta neuropathologica communications · 2025Article
- Single nuclei transcriptomics reveals cellular diversity in TSC subependymal giant cell astrocytomas.iScience · 2025Article
- Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome.Human molecular genetics · 2025Article
- Progressive Alcohol-Related Brain Atrophy and White Matter Pathology Are Linked to Long-Term Inhibitory Effects on mTOR Signaling.Biomolecules · 2025Article
- Review
- The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.Genes & diseases · 2024Review
- Differential effects of moderate chronic ethanol consumption on neurobehavior, white matter glial protein expression, and mTOR pathway signaling with adolescent brain maturation.The American journal of drug and alcohol abuse · 2024Article
- Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome.bioRxiv : the preprint server for biology · 2024Article
- Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit.Journal of neurodevelopmental disorders · 2024Article
- The role of TSC1 and TSC2 proteins in neuronal axons.Molecular psychiatry · 2024Review
- Amelioration of the brain structural connectivity is accompanied with changes of gut microbiota in a tuberous sclerosis complex mouse model.Translational psychiatry · 2024Article
- Rodent Models for ASD Biomarker Development.Advances in neurobiology · 2024Review
- Dysregulated mTOR networks in experimental sporadic Alzheimer's disease.Frontiers in cellular neuroscience · 2024Article
- Rescue of Impaired Blood-Brain Barrier in Tuberous Sclerosis Complex Patient Derived Neurovascular Unit.bioRxiv : the preprint server for biology · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWhile abnormalities in myelin in tuberous sclerosis complex (TSC) have been known for some time, recent imaging-based data suggest myelin abnormalities may be independent of the pathognomonic cortical lesions ("tubers"). Multiple mouse models of TSC exhibit myelination deficits, though the cell types responsible and the mechanisms underlying the myelin abnormalities remain unclear.
methodsTo determine the role of alterations in mTOR signaling in myelination, we generated a conditional knockout (CKO) mouse model using Cre-recombinase and the Olig2 promoter to inactivate the Tsc2 gene in oligodendrocyte precursor cells.
resultsCharacterization of myelin and myelin constituent proteins demonstrated a marked hypomyelination phenotype. Diffusion-based magnetic resonance imaging studies were likewise consistent with hypomyelination. Hypomyelination was due in part to decreased myelinated axon density and myelin thickness as well as decreased oligodendrocyte numbers. Coincident with hypomyelination, an extensive gliosis was seen in both the cortex and white matter tracks, suggesting alterations in cell fate due to changes in mTOR activity in oligodendrocyte precursors. Despite a high-frequency appendicular tremor and altered gait in CKO mice, no significant changes in activity, vocalizations, or anxiety-like phenotypes were seen.
interpretationOur findings support a known role of mTOR signaling in regulation of myelination and demonstrate that increased mTORC1 activity early in development within oligodendrocytes results in hypomyelination and not hypermyelination. Our data further support a dissociation between decreased Akt activity and increased mTORC1 activity toward hypomyelination. Thus, therapies promoting activation of Akt-dependent pathways while reducing mTORC1 activity may prove beneficial in treatment of human disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.