The Exciting Frontier of Neuroplasticity: Innovations in Brain Health and Recovery

Journal of Behavioral and Brain Science, Год журнала: 2025, Номер 15(03), С. 47 - 80

Опубликована: Янв. 1, 2025

Язык: Английский

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Paroxetine ameliorates corticosterone-induced myelin damage by promoting the proliferation and differentiation of oligodendrocyte precursor cells

Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Extracellular vesicles as precision therapeutics for psychiatric conditions: targeting interactions among neuronal, glial, and immune networks

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

The critical role of the immune system in brain function and dysfunction is well recognized, yet development therapies for psychiatric diseases has been slow due to concerns about iatrogenic deficiencies. These are emphasized by lack objective diagnostic tools psychiatry. A promise resolve this conundrum lies exploitation extracellular vesicles (EVs) that physiologically produced or can be synthetized. EVs regulate recipient cell functions offer potential EVs-based therapies. Intranasal administration enables targeting specific regions functions, thereby facilitating design precise treatments diseases. such requires navigating four dynamically interacting networks: neuronal, glial, immune, EVs. networks profoundly influenced fluid distribution. They crucial homeostasis, cellular intercellular communication. Fluid abnormalities, like edema altered cerebrospinal (CSF) dynamics, disrupt these networks, negatively impacting health. deeper understanding above-mentioned vital creating biomarker panels identify distinct patient subsets with similar neuro-behavioral symptoms. Testing functional pathways biomarkers could lead new therapeutic tools. Regulatory approval will depend on robust preclinical data reflecting progress interdisciplinary areas, which pave way innovative treatments. Highly collaborative teams needed achieve ambitious goals.

Язык: Английский

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The neuroplastic brain: current breakthroughs and emerging frontiers

Brain Research, Год журнала: 2025, Номер unknown, С. 149643 - 149643

Опубликована: Апрель 1, 2025

Язык: Английский

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Oligodendrogenesis in Evolution, Development and Adulthood

Glia, Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

ABSTRACT Oligodendrogenesis and myelin formation are important processes in the central nervous system (CNS) of jawed vertebrates, underpinning highly efficient neural computation within compact CNS architecture. Myelin, dense lipid sheath wrapped around axons, enables rapid signal transmission modulation circuits. Oligodendrocytes generated from oligodendrocyte precursor cells (OPCs), which widely distributed adult continue to produce new oligodendrocytes throughout life. Adult oligodendrogenesis is integral adaptive myelination, fine‐tunes circuits response neuronal activity, contributing neuroplasticity, learning, memory. Emerging evidence also highlights role specialized brain regions, linking metabolic homeostatic functions. In aging diseased brain, dysregulated exacerbates loss may contribute pathogenesis. addition, maladaptive myelination driven by aberrant activity could sustain a dysfunction conditions such as epilepsy. This review summarizes current understanding oligodendrogenesis, with insights into its evolution, regulation, impact on disease.

Язык: Английский

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Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy

Genes, Год журнала: 2025, Номер 16(5), С. 590 - 590

Опубликована: Май 17, 2025

Background: X-ALD is a white matter (WM) disease caused by mutations in the ABCD1 gene encoding transporter of very-long-chain fatty acids (VLCFAs) into peroxisomes. Strikingly, same mutation causes either devastating brain inflammatory demyelination during childhood or, more often, progressive spinal cord axonopathy starting middle-aged adults. The accumulation undegraded VLCFA glial cell membranes and myelin has long been thought to be central mechanism X-ALD. Methods: This review discusses studies mouse drosophila models that have modified our views pathogenesis. Results: In Abcd1 knockout (KO) mimics disease, late manifestations are rapidly reversed transfer oligodendrocytes (OLs). peroxin-5 KO model, selective impairment peroxisomal biogenesis OLs achieves an almost perfect phenocopy cerebral ALD. A model revealed myelinating cells production toxic lipid able poison axons activate cells. Other showed critical role providing energy substrates axons. addition, on microglial changing substates improved understanding neuroinflammation. Conclusions: Animal supporting primary axonal pathology secondary microglia allow us revisit mechanisms. Beyond mutations, pathogenesis depends unidentified contributors, such as genetic background, cell-specific epigenomics, potential environmental triggers, stochasticity crosstalk between multiple types among billions neurons.

Язык: Английский

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Pathways to Progressive Disability in Multiple Sclerosis: The Role of Glial Cells in Chronic CNS Inflammation

Glia, Год журнала: 2025, Номер unknown

Опубликована: Май 23, 2025

ABSTRACT Multiple sclerosis (MS) is the most common non‐infectious inflammatory CNS disease, characterized by progressive neurodegeneration and focal demyelinated lesions. Traditionally considered an autoimmune MS driven immune system's attack on myelin, resulting in cumulative disability. However, conventional anti‐inflammatory treatments often fail to prevent deterioration, particularly absence of overt inflammation, highlighting need for a deeper understanding its pathogenesis. Recent research has revealed more complex disease mechanism involving both peripheral responses intrinsic factors, with glial cells playing central role. Persistent inflammation associated mixed active/inactive lesions dominated microglia astrocyte dysregulation. These populations exhibit maladaptive activation, contributing failed remyelination ongoing neurodegeneration. Transcriptomic epigenomic alterations as well aging further exacerbate dysfunction, creating self‐perpetuating cycle damage. Emerging evidence suggests that interplay between potential dual‐use nature molecular tools shared system disrupts homeostatic signaling, leading loss tissue integrity. This review synthesizes findings cell biology MS, focus astrocytes, while addressing their roles demyelination, synapse loss, The limitations animal models, EAE, replicating complexity are also addressed. Finally, critical questions outlined guide future into pathology identify novel therapeutic approaches targeting MS.

Язык: Английский

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Human iPSC-derived myelinating organoids and globoid cells to study Krabbe Disease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

Abstract Krabbe disease (Kd) is a lysosomal storage disorder (LSD) caused by the deficiency of galactosylceramidase (GALC) which cleaves myelin enriched lipid galactosylceramide (GalCer). Accumulated GalCer catabolized into cytotoxic psychosine that causes myelinating cells death and demyelination recruits microglia/macrophages fail to digest debris become globoid cells. Here, understand pathological mechanisms Kd, we used induced pluripotent stem (iPSCs) from Kd patients produce organoids microglia. We show have no obvious defects in neurogenesis, astrogenesis, oligodendrogenesis but manifest early myelination defects. Specifically, showed shorter similar number internodes than Controls at peak reduced later time point. Interestingly, affected absence autophagy mTOR pathway dysregulation, suggesting lack dysfunction makes this organoid model very valuable tool study events drive Kd. iPSC-derived microglia marginal rate cell formation under normal culture conditions drastically increased upon feeding. Under conditions, minor LAMP1 content decrease slight increase protein LC3B. Upon feeding, accumulation proteins strong reduction point are reverted showing compensatory capabilities Altogether, supports value our cultures as tools mechanism play overcome

Язык: Английский

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Human iPSC-derived myelinating organoids and globoid cells to study Krabbe disease

PLoS ONE, Год журнала: 2024, Номер 19(12), С. e0314858 - e0314858

Опубликована: Дек. 5, 2024

Krabbe disease (Kd) is a lysosomal storage disorder (LSD) caused by the deficiency of galactosylceramidase (GALC) which cleaves myelin enriched lipid galactosylceramide (GalCer). Accumulated GalCer catabolized into cytotoxic psychosine that causes myelinating cells death and demyelination recruits microglia/macrophages fail to digest debris become globoid cells. Here, understand pathological mechanisms Kd, we used induced pluripotent stem (iPSCs) from Kd patients produce organoids microglia. We show have no obvious defects in neurogenesis, astrogenesis, oligodendrogenesis but manifest early myelination defects. Specifically, showed shorter similar number internodes than Controls at peak reduced later time point. Interestingly, affected absence autophagy mTOR pathway dysregulation, suggesting lack dysfunction makes this organoid model very valuable tool study events drive Kd. iPSC-derived microglia marginal rate cell formation under normal culture conditions drastically increased upon feeding. Under conditions, minor LAMP1 content decrease slight increase protein LC3B. Upon feeding, accumulation proteins strong reduction point are reverted showing compensatory capabilities Altogether, supports value our cultures as tools mechanism play overcome

Язык: Английский

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A new gatekeeper to control oligodendrogenesis

PLoS Biology, Год журнала: 2024, Номер 22(7), С. e3002691 - e3002691

Опубликована: Июль 11, 2024

The diversity of oligodendrocyte precursor cells (OPCs) is not well understood and actively discussed in the field. A new study PLOS Biology describes a novel marker for an OPC subpopulation that controls oligodendrogenesis myelination.

Язык: Английский

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