Metabolomics Profile of the Secretome of Space-Flown Oligodendrocytes DOI Creative Commons
Laurent Vergnes,

Bernard Foucaud,

Carlos Cepeda

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(18), P. 2249 - 2249

Published: Sept. 11, 2023

Intracranial hypertension (ICP) and visual impairment intracranial pressure (VIIP) are some of the sequels long-term space missions. Here we sought to determine how microgravity (µG) impacts metabolomics profile oligodendrocyte progenitors (OLPs), myelin-forming cells in central nervous system. We report increased glutamate energy metabolism while OLPs were for 26 days. also show that after flight, (SPC OLPs) display significantly mitochondrial respiration glycolysis. These data agreement with our previous work using simulated microgravity. In addition, global approach allowed discovery endogenous metabolites secreted by modulated Our results provide, first time, relevant information about energetic state flight. The functional molecular relevance these specific pathways promising targets therapeutic intervention humans missions moon, Mars beyond.

Language: Английский

Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis DOI Open Access
Eneritz López-Muguruza, Carlos Matute

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12912 - 12912

Published: Aug. 18, 2023

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play vital role in maintaining integrity myelin, protective sheath around nerve fibres essential for efficient signal transmission. However, MS, oligodendrocytes become dysfunctional, leading to myelin damage axonal degeneration. Emerging evidence suggests that metabolic changes, including mitochondrial dysfunction alterations glucose lipid metabolism, contribute significantly pathogenesis MS. Mitochondrial observed both immune cells within CNS MS patients. Impaired function leads energy deficits, affecting crucial processes such as impulse transmission transport, ultimately contributing Moreover, linked generation reactive oxygen species (ROS), exacerbating inflammation. Altered metabolism affects supply required oligodendrocyte synthesis. Dysregulated results changes composition its stability integrity. Importantly, low levels polyunsaturated fatty acids are associated with upregulated enhanced catabolism. Understanding intricate relationship between these mechanisms developing targeted therapies preserve promote neurological recovery individuals Addressing aspects may offer new insights into potential therapeutic strategies halt progression improve quality life

Language: Английский

Citations

39
Reversible reduction in brain myelin content upon marathon running DOI Creative Commons
Pedro Ramos‐Cabrer, Alberto Cabrera‐Zubizarreta, Daniel Padró

et al.

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Here we use magnetic resonance imaging to study the impact of marathon running on brain structure in humans. We show that signal for myelin water fraction—a surrogate content—is substantially reduced upon specific regions involved motor coordination and sensory emotional integration, but recovers within two months. These findings suggest content is temporarily reversibly diminished by severe exercise, a finding consistent with recent evidence from rodent studies lipids may act as glial energy reserves extreme metabolic conditions. Using runners, Ramos-Cabrer, Cabrera-Zubizarreta et al. report detected significantly after fully recovered

Language: Английский

Citations

1
Complex II ambiguities—FADH2 in the electron transfer system DOI Creative Commons
Erich Gnaiger

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 300(1), P. 105470 - 105470

Published: Nov. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Language: Английский

Citations

19
Seipin deficiency-induced lipid dysregulation leads to hypomyelination-associated cognitive deficits via compromising oligodendrocyte precursor cell differentiation DOI Creative Commons
Wenli Cui, Jing Yang,

Chuanyun Tu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 21, 2024

Abstract Seipin is one key mediator of lipid metabolism that highly expressed in adipose tissues as well the brain. Lack gene, Bscl2 , leads to not only severe metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly lipids, facilitates nerve transmission important for coordination learning. Whether deficiency-leaded defects learning underlined by dysregulation its consequent myelin abnormalities remains be elucidated. In present study, we verified expression oligodendrocytes (OLs) their precursors, oligodendrocyte precursor cells (OPCs), demonstrated deficiency compromised OPC differentiation, which led decreased OL numbers, protein, myelinated fiber proportion thickness myelin. Deficiency resulted impaired spatial cognition mice. Mechanistically, suppressed sphingolipid metabolism-related genes OPCs caused morphological droplets (LDs), markedly impeded differentiation. Importantly, rosiglitazone, agonist PPAR-gamma, substantially restored phenotypes resulting from deficiency, such aberrant LDs, reduced sphingolipids, obstructed neurobehavioral defects. Collectively, study elucidated how deficiency-induced deficits via impairing myelination, may pave way developing novel intervention strategy treating metabolism-involved neurological disorders.

Language: Английский

Citations

6
Inflammaging and Brain Aging DOI Open Access
Maria Carolina Jurcău, Anamaria Jurcău,

Alexander Cristian

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10535 - 10535

Published: Sept. 30, 2024

Progress made by the medical community in increasing lifespans comes with costs of incidence and prevalence age-related diseases, neurodegenerative ones included. Aging is associated a series morphological changes at tissue cellular levels brain, as well impairments signaling pathways gene transcription, which lead to synaptic dysfunction cognitive decline. Although we are not able pinpoint exact differences between healthy aging neurodegeneration, research increasingly highlights involvement neuroinflammation chronic systemic inflammation (inflammaging) development age-associated via pathogenic cascades, triggered dysfunctions circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender susceptibility course neurodegeneration that appear be mediated glial cells emphasize need for future this area an individualized therapeutic approach. rejuvenation still its very early infancy, accumulated knowledge on various involved promoting senescence opens perspective interfering these preventing delaying senescence.

Language: Английский

Citations

6
Functions and dysfunctions of oligodendrocytes in neurodegenerative diseases DOI Creative Commons

Seung-Wan Han,

Yunho Gim,

Eun‐Hae Jang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Dec. 20, 2022

Neurodegenerative diseases (NDDs) are characterized by the progressive loss of selectively vulnerable populations neurons, which is responsible for clinical symptoms. Although degeneration neurons a prominent feature that undoubtedly contributes to and defines NDD pathology, it now clear neuronal cell death no means mediated solely cell-autonomous mechanisms. Oligodendrocytes (OLs), myelinating cells central nervous system (CNS), enable rapid transmission electrical signals provide metabolic trophic support neurons. Recent evidence suggests OLs their progenitor population play role in onset progression NDDs. In this review, we discuss emerging suggesting OL lineage pathogenesis age-related We start with multiple atrophy, an well-known oligodendroglial then Alzheimer's disease (AD) Parkinson's (PD), NDDs have been thought as origins. Understanding functions dysfunctions might lead advent disease-modifying strategies against

Language: Английский

Citations

26
Mitochondrial dysfunction in cognitive neurodevelopmental disorders: Cause or effect? DOI
Ayyappan Anitha, Ismail Thanseem, Mary Iype

et al.

Mitochondrion, Journal Year: 2023, Volume and Issue: 69, P. 18 - 32

Published: Jan. 6, 2023

Language: Английский

Citations

15
Oligodendrocytes in central nervous system diseases: the effect of cytokine regulation DOI Creative Commons
Chengfu Zhang, Mengsheng Qiu, Hui Fu

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 8, 2024

Abstract Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines involved nearly every aspect of cellular functions such as migration, survival, proliferation, differentiation. Oligodendrocytes the myelin-forming cells central nervous system play critical roles conduction action potentials, supply metabolic components for axons, other functions. Emerging evidence suggests that both oligodendrocytes oligodendrocyte precursor vulnerable to released under pathological conditions. This review mainly summarizes effects on lineage A comprehensive understanding contributes our diseases offers insights into treatment strategies.

Language: Английский

Citations

5
The α- to γ-enolase switch: The role and regulation of γ-enolase during oligodendrocyte differentiation DOI Creative Commons

Selena Horvat,

Urša Pečar Fonović,

Ana Mitrović

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140464 - 140464

Published: Jan. 1, 2025

The glycolytic enzyme γ-enolase is a highly specific neuronal marker that known to replace ubiquitously expressed α-enolase in the brain. Moreover, has been shown exert neurotrophic activity, which regulated by cathepsin X, lysosomal peptidase. This study investigates role of and its regulation X during differentiation oligodendrocytes, are essential for normal brain function. We established protocol human oligodendroglioma (HOG) cell line demonstrated first time an α- switch occurs HOG differentiation. was confirmed expression markers underscoring oligodendrocyte overexpression enhanced differentiation, while silencing siRNA significantly decreased maturation marker. Further, regulatory cysteine peptidase on function found. Silencing changed morphology, altered markers, increased levels active form γ-enolase. Inhibiting similarly morphology These findings suggest modulates activity thereby influences thus

Language: Английский

Citations

0
The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration DOI Creative Commons
Katherine Fodder, Rohan de Silva, Thomas T. Warner

et al.

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: June 29, 2023

Neurodegenerative diseases encompass a heterogeneous group of conditions characterised by the progressive degeneration structure and function central or peripheral nervous systems. The pathogenic mechanisms underlying these are not fully understood. However, feature consists regional aggregation proteins in brain, such as accumulation β-amyloid plaques Alzheimer's disease (AD), inclusions hyperphosphorylated microtubule-binding tau AD other tauopathies, containing α-synuclein Parkinson's (PD), dementia with Lewy bodies (DLB) multiple system atrophy (MSA). Various thought to contribute disease, an increasing number studies implicate dysfunction oligodendrocytes (the myelin producing cells system) loss. Aberrant DNA methylation, most widely studied epigenetic modification, has been associated many neurodegenerative diseases, including AD, PD, DLB MSA, recent findings highlight aberrant methylation oligodendrocyte/myelin-related genes. Here we briefly review evidence showing that changes key neurodegeneration, explore relevance oligodendrocyte (dys)function. As is reversible, elucidating its involvement specific cell-types may bring opportunities for therapeutic interventions diseases.

Language: Английский

Citations

11