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

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 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.

Language: Английский

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Neuroglial decline defines cognitive ageing

Ageing & Longevity, Journal Year: 2025, Volume and Issue: 1.2025, P. 6 - 21

Published: Jan. 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;

Language: Английский

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The influence of sex difference on behavior and adult hippocampal neurogenesis in C57BL/6 mice

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 12, 2023

Animal models have been used extensively in vivo studies, especially within the biomedical field. Traditionally, single-sex mostly males, are to avoid any potential confounding variation caused by sex difference and female estrous cycle. Historically, animal subjects believed exhibit higher variability, this could increase statistical power needed test a hypothesis. This study sets out evaluate whether does exist mouse behavior, mice featured variability. We assessed sensorimotor skills, anxiety-like depression-like cognitive abilities of through series commonly behavioral tests. Except for stronger grip force lower tactile sensory sensitivity detected male mice, there was no significant between males females other Furthermore, immunolabeling neurogenesis markers suggested sexes adult hippocampal neurogenesis. Within group variances were equivalent; did not variability than males. However, overall negative results be due limitation small sample size. In conclusion, our provides evidence that significantly influence these tests nor under basal conditions. suggest also considered inclusion future experiment design.

Language: Английский

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Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies

Frontiers in Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 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.

Language: Английский

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Sodium homeostasis and signalling: The core and the hub of astrocyte function

Cell Calcium, Journal Year: 2023, Volume and Issue: 117, P. 102817 - 102817

Published: Nov. 4, 2023

Language: Английский

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Neuroglia in cognitive reserve

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: July 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.

Language: Английский

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Astrocytic chloride regulates brain function in health and disease

Cell Calcium, Journal Year: 2024, Volume and Issue: 118, P. 102855 - 102855

Published: Feb. 7, 2024

Chloride ions (Cl−) play a pivotal role in synaptic inhibition the central nervous system, primarily mediated through ionotropic mechanisms. A recent breakthrough emphathizes significant influence of astrocytic intracellular chloride concentration ([Cl−]i) regulation, field still its early stages exploration. Typically, [Cl−]i most animal cells is maintained at lower levels than extracellular [Cl−]o, critical balance to prevent cell swelling due osmotic pressure. Various Cl− transporters are expressed differently across types, fine-tuning [Cl−]i, while gradients utilised by several families channels. Although passive distribution within governed basic biophysical principles, astrocytes actively expend energy sustain much higher those achieved passively, and neuronal [Cl−]i. Beyond volume dynamically linked brain states influences signalling behaving animals. As vital component function, also plays development disorders where inhibitory transmission disrupted. This review synthesises latest insights into elucidating modulating function implications various pathophysiological conditions.

Language: Английский

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Electrospun Polycaprolactone (PCL) Nanofibers Induce Elongation and Alignment of Co-Cultured Primary Cortical Astrocytes and Neurons

Micromachines, Journal Year: 2025, Volume and Issue: 16(3), P. 256 - 256

Published: Feb. 25, 2025

Neuromimetic in vitro models, simulating vivo architecture/organization, are urgently needed to reduce experimental reliance on live animals. Our group recently reported a novel brain tissue derivation protocol, simultaneously deriving all major cortical cell types (including immune cells) facile generating network of neurons single growth medium, which was interfaced with nanomaterials. This represents significant advance, as engineers overwhelmingly use diverse methods derive and combine individual cells for materials-interfacing. However, this multicellular model lacked cellular directionality/structural organization (unlike the highly organized circuits vivo). Synthetic nanofiber constructs high value engineering, providing directional cues cells. Most neuro-nanofiber studies employ simple monocultures astrocytes/neurons commonly peripheral rather than central nervous system populations. Here, we have our complex (neurons/astrocytes derived simultaneously) randomly oriented or aligned polycaprolactone (PCL) fiber meshes. Both showed targeted extension along fibers versus coverslips random fibers. A new analysis method developed in-house demonstrated that peak orientations astrocytes correlated nanofibers. data support concept scaffolds can achieve mixed neural populations, mimicking architecture.

Language: Английский

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Evolution of neuroglia: From worm to man

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 7 - 26

Published: Jan. 1, 2025

Language: Английский

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Neuroglia in aging

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 49 - 67

Published: Jan. 1, 2025

Language: Английский

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