Astrocytes in human central nervous system diseases: a frontier for new therapies

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Язык: Английский

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Neuroglial decline defines cognitive ageing

Ageing & Longevity, Год журнала: 2025, Номер 1.2025, С. 6 - 21

Опубликована: Янв. 17, 2025

Neuroglia of the central nervous system, represented by astroglia, oligodendroglia and microglia, are fundamental for life-long support homeostasis, plasticity defence neural tissue. In particular neuroglial cells contribute to cognitive reserve, which defines neurological outcome both physiological pathological ageing. Physiological ageing is accompanied with structural functional decline neuroglia. particular, astrocytes undergo morphological atrophy asthenia compromises their vital functions such as glutamate clearance, K+ buffering synaptic support. Old oligodendrocytes lose myelination capacity, results in thinning myelin sheath white matter. Finally, associated accumulation dystrophic microglia limits neuroprotection. Age-dependent impedes contributes impairment, increases vulnerability system neurodegeneration. Life style changes positively impact on structure function this improving longevity. Keywords: ageing; longevity; neuroglia, oligodendroglia; oligodendroglial precursor cells;

Язык: Английский

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Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12912 - 12912

Опубликована: Авг. 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

Язык: Английский

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Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies

Frontiers in Integrative Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Фев. 19, 2024

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation nervous system by precise delivery electrical current for treatment conditions, such post-stroke movement recovery or drug-resistant disorders. The unquestionable impact is underscored successful translation to humans in last decades, long list preclinical studies. Given emergency accelerating progress new neuromodulation treatments (i.e., hypertension, autoimmune degenerative diseases), collaboration between multiple fields imperative. This work intends foster multidisciplinary bring together different provide fundamental basis underlying Medicine. In this review we will go from biophysics cell membrane, which consider inner core neuromodulation, patient care. We discuss recently discovered mechanism neurotransmission switching how it design, update on neuronal glial health disease. advances biomedical technology have facilitated collection large amounts data, thereby introducing challenges data analysis. approaches high throughput analysis, encompassing big networks, artificial intelligence, internet things. Emphasis be placed understanding electrochemical properties neural interfaces, along with integration biocompatible reliable materials compliance regulations translational applications. Preclinical validation foundational process, critical aspects animal Finally, focus point-of-care ultimate goal bioelectronic medicine. a call scientists common endeavor: accelerate decoding era therapeutic possibilities.

Язык: Английский

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TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(4)

Опубликована: Апрель 1, 2024

White matter injury (WMI) is an important pathological process after traumatic brain (TBI). The correlation between white functions and the myeloid cells expressing triggering receptor-2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism crucial for early remyelination demyelinating diseases. However, potential roles of TREM2 expression in WMI TBI have not yet explored.

Язык: Английский

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Neuroglia in cognitive reserve

Molecular Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Июль 2, 2024

Abstract The concept of cognitive reserve was born to account for the disjunction between objective extent brain damage in pathology and its clinical intellectual outcome. comprises structural (brain reserve) functional maintenance, resilience, compensation) aspects nervous tissue reflecting exposome-driven life-long plasticity, which defines ability withstand aging pathology. mechanistic background this primarily focused on adaptive changes neurones neuronal networks. We present arguments favoring more inclusive view, positing that neuroglia are fundamental defining through homeostatic, neuroprotective, neurodegenerative mechanisms. Neuroglia critical shaping synaptically connected circuits as well connectome thus reserve. Neuroglial homeostatic protective physiological responses define maintenance while regenerative capabilities compensation Targeting may represent an untrodden path prolonging longevity.

Язык: Английский

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Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Июль 3, 2024

Abstract Background Understanding the mechanism behind sepsis-associated encephalopathy (SAE) remains a formidable task. This study endeavors to shed light on complex cellular and molecular alterations that occur in brains of mouse model with SAE, ultimately unraveling underlying mechanisms this condition. Methods We established murine using intraperitoneal injection lipopolysaccharide (LPS) wild type Anxa1 −/− mice collected brain tissues for analysis at 0-hour, 12-hour, 24-hour, 72-hour post-injection. Utilizing advanced techniques such as single-nucleus RNA sequencing (snRNA-seq) Stereo-seq, we conducted comprehensive characterization responses patterns within brain. Results Our uncovered notable temporal differences response LPS challenge between (annexin A1 knockout) mice, specifically 12-hour 24-hour time points following injection. observed significant increase proportion Astro-2 Micro-2 cells these mice. These exhibited colocalization pattern vascular subtype Vas-1, forming distinct region known V1A2M2, where surrounded Vas-1. Moreover, through further analysis, discovered upregulation ligands receptors Timp1-Cd63 , Timp1-Itgb1 Timp1-Lrp1 well Ccl2-Ackr1 Cxcl2-Ackr1 region. In addition, expression Cd14-Itgb1 Cd14-Tlr2 Cd14-C3ar1 regions enriched cells. Additionally, Cxcl10-Sdc4 showed broad containing both Notably, upon challenge, there was an Furthermore, our revealed noteworthy mortality rates knockdown. However, did not observe substantial types, numbers, or distribution other wildtype over time. Nevertheless, when comparing post point, decrease vicinity blood vessels noted reduced levels several ligand-receptor pairs including . Conclusions By combining snRNA-seq Stereo-seq techniques, successfully identified distinctive colocalization, referred special pathological niche, comprising Astro-2, Micro-2, Vas-1 niche. findings suggest potential association arrangement contributing SAE increased knockdown

Язык: Английский

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A New Acquaintance of Oligodendrocyte Precursor Cells in the Central Nervous System

Neuroscience Bulletin, Год журнала: 2024, Номер 40(10), С. 1573 - 1589

Опубликована: Июль 23, 2024

Язык: Английский

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Small Molecule Hydrogels Loading Small Molecule Drugs from Chinese Medicine for the Enhanced Treatment of Traumatic Brain Injury

ACS Nano, Год журнала: 2024, Номер 18(42), С. 28894 - 28909

Опубликована: Окт. 9, 2024

Self-assembly of hydrogels for mechanical support and drug delivery has been extensively researched in traumatic brain injury (TBI), where treatment options are limited. The chief challenge is that most self-assembled rely on high molecular carriers or the incorporation exogenous inactive substances as mediators. It difficult these systems to achieve clinical translation due concerns regarding biological safety. Here we report a small molecule hydrogel (GBR-gel) loading drugs (glycyrrhizic acid, berberine, rhein) originated from popular Chinese medicines without additional components under physiological conditions. In long run, GBR-gel possesses several advantages, including ease preparation, cost-effectiveness, biocompatibility. As proof-of-concept, allows prompt administration at site exert potent pharmacodynamic effects. Further single-cell RNA sequencing experimental validation indicated can effectively rescue suppressed glutamatergic synapse pathway after TBI, thereby attenuating inflammatory responses neural impairments. Our work provides an alternative strategy timely intervention TBI.

Язык: Английский

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Glial cell deficits are a key feature of schizophrenia: implications for neuronal circuit maintenance and histological differentiation from classical neurodegeneration

Molecular Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Abstract Dysfunctional glial cells play a pre-eminent role in schizophrenia pathophysiology. Post-mortem studies have provided evidence for significantly decreased cell numbers different brain regions of individuals with schizophrenia. Reduced are most pronounced oligodendroglia, but reduced astrocyte densities also been reported. This review highlights that oligo- and astroglial deficits key histopathological feature schizophrenia, distinct from typical changes seen neurodegenerative disorders. Significant oligodendrocytes may arise two ways: (i) demise mature functionally compromised oligodendrocytes; (ii) lack due to failed maturation progenitor cells. We analyse detail the controversy regarding astrocytes. Regardless their origin, several pathophysiological consequences. Among these, myelination number be important factor, resulting disconnectivity between neurons observed When die, it appears through degeneration, process which is basically reversible. Thus, therapeutic interventions help rescue or improve might viable option. Since antipsychotic treatment alone does not seem prevent loss deficits, there intense search new options. Current proposals range application antidepressants other chemical agents as well physical exercise engrafting healthy into brains patients.

Язык: Английский

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