Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 16, 2023

How aging affects cells of the human brain active milieu remains largely unknown. Here, we analyze astrocytes and neurons in neocortical tissue younger (22-50 years) older (51-72 adults. Aging decreases amount reduced mitochondrial cytochromes but not neurons. The protein-to-lipid ratio increases Aged show morphological atrophy quantified by decreased length branches, volume fraction leaflets, shrinkage anatomical domain. Atrophy correlates with loss gap junction coupling between increased input resistance. is accompanied upregulation glial fibrillary acidic protein (GFAP) downregulation membrane-cytoskeleton linker ezrin associated leaflets. No significant changes neuronal excitability or spontaneous inhibitory postsynaptic signaling observed. Thus, impaired presence malfunction cortical astrocytes,

Language: Английский

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Organizing principles of astrocytic nanoarchitecture in the mouse cerebral cortex

Current Biology, Journal Year: 2023, Volume and Issue: 33(5), P. 957 - 972.e5

Published: Feb. 16, 2023

Language: Английский

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A high‐fat diet changes astrocytic metabolism to promote synaptic plasticity and behavior

Acta Physiologica, Journal Year: 2022, Volume and Issue: 236(1)

Published: June 2, 2022

Abstract Aim A high‐fat diet (HFD) is generally considered to negatively influence the body, brain, and cognition. Nonetheless, fat fatty acids are essential for nourishing constructing brain tissue. Astrocytes central lipolysis metabolism. We tested how HFD affects astrocyte metabolism, morphology, physiology. Methods used Raman microspectroscopy assess redox state of mitochondria lipid content in astrocytes neurons hippocampal slices mice subjected HFD. were loaded with fluorescent dye through patch pipette morphological analysis. Whole‐cell voltage‐clamp recordings performed measure transporter potassium currents. Western blot analysis quantified expression astrocyte‐specific proteins. Field potential measured magnitude long‐term potentiation (LTP). Open filed test was evaluate effect on animal behavior. Results found that exposure young 1 month increases relative amount reduced cytochromes but not neurons. Metabolic changes paralleled an enlargement astrocytic territorial domains due increased outgrowth branches leaflets. Astrocyte remodeling associated increase ezrin no glial fibrillary acidic protein (GFAP), glutamate transporter‐1 (GLT‐1), glutamine synthetase (GS). Such physiological (non‐reactive) active milieu promoted clearance LTP translated into behavioral changes. Conclusion Dietary intake invariably harmful might exert beneficial effects depending biological context.

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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How astrocytic chloride modulates brain states

BioEssays, Journal Year: 2024, Volume and Issue: 46(6)

Published: April 14, 2024

Abstract The way the central nervous system (CNS) responds to diverse stimuli is contingent upon specific brain state of individual, including sleep and wakefulness. Despite wealth readout parameters data delineating states, primary mechanisms are yet be identified. Here we highlight role astrocytes, with a emphasis on chloride (Cl − ) homeostasis as modulator states. Neuronal activity regulated by concentration ions that determine excitability. Astrocytes, CNS homeostatic cells, recognised for their proficiency in maintaining dynamic ions, known ionostasis. Nevertheless, contribution astrocyte‐driven ionostasis genesis states or response sleep‐inducing pharmacological agents has been overlooked. Our objective underscore significance astrocytic Cl homeostasis, elucidating how it may underlie modulation We endeavour contribute comprehensive understanding interplay between astrocytes

Language: Английский

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Distribution Patterns of Astrocyte Populations in the Human Cortex

Neurochemical Research, Journal Year: 2022, Volume and Issue: 48(4), P. 1222 - 1232

Published: Aug. 5, 2022

Astrocytes are a major class of glial cell in the central nervous system that have diverse range types and functions thought to be based on their anatomical location, morphology cellular properties. Recent studies highlight astrocyte dysfunction contributes pathogenesis neurological conditions. However, few described pattern, distribution density astrocytes adult human cortex. This study mapped immunolabelled with cytoskeletal membrane markers frontal Distinct overlapping populations were determined. The cortex from ten normal control cases (75 ± 9 years) was immunostained fibrillary acidic protein (GFAP), aldehyde dehydrogenase-1 L1 (ALDH1L1), connexin-43 (Cx43), aquaporin-4 (AQP4), glutamate transporter 1 (GLT-1). All labelled grey white matter, separate cortical layers, subpial perivascular regions. informative for labelling different properties compartments astrocytes. ALDH1L1 largest population astrocytes, Cx43-immunopositive found all layers. AQP4 GLT-1 distal astrocytic process end-feet same (98% GLT-1-immunopositive contained AQP4). In contrast, GFAP, most widely used marker, predominantly superficial highlights diversity cortex, providing reference map distinct which can comparative purposes various disease, inflammatory injury states involving

Language: Английский

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Role of Senescent Astrocytes in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8498 - 8498

Published: May 9, 2023

For many decades after their discovery, astrocytes, the abundant glial cells of brain, were believed to work as a glue, supporting structure and metabolic functions neurons. A revolution that started over 30 years ago revealed additional these cells, including neurogenesis, gliosecretion, glutamate homeostasis, assembly function synapses, neuronal metabolism with energy production, others. These properties have been confirmed, limited however, proliferating astrocytes. During aging or following severe brain stress lesions, astrocytes are converted into no-longer-proliferating, senescent forms, similar in morphology but profoundly modified functions. The changed specificity is largely due altered gene expression. ensuing effects include downregulation typical upregulation others, concerned neuroinflammation, release pro-inflammatory cytokines, dysfunction etc., specific senescence program. decrease support protection by induces development, vulnerable regions, toxicity together cognitive decline. Similar changes, ultimately reinforced astrocyte aging, also induced traumatic events molecules involved dynamic processes. Senescent play critical roles development diseases. first demonstration, obtained for Alzheimer’s disease less than 10 ago, contributed elimination previously predominant neuro-centric amyloid hypothesis. initial effects, operating considerable time before appearance known symptoms evolve severity up proliferation during final outcome. Involvement other neurodegenerative diseases cancer now intensely investigated.

Language: Английский

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Physiology of neuroglia of the central nervous system

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 69 - 91

Published: Jan. 1, 2025

Language: Английский

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Neuroglia in stroke

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 101 - 111

Published: Jan. 1, 2025

Language: Английский

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Physiology and pathophysiology of the retinal neuroglia

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 239 - 265

Published: Jan. 1, 2025

Language: Английский

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