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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NKCC1 Inhibition Improves Sleep Quality and EEG Information Content in a Down Syndrome Mouse Model

iScience, Journal Year: 2025, Volume and Issue: 28(4), P. 112220 - 112220

Published: March 14, 2025

In several brain disorders, the hyperpolarizing/inhibitory effects of GABA signaling through Cl-permeable GABAA receptors are compromised, leading to an imbalance between neuronal excitation and inhibition. For example, Ts65Dn mouse model Down syndrome (DS) exhibits increased expression Cl- importer NKCC1, depolarizing gamma aminobutyric acid (GABA) in mature hippocampus cortex. Inhibiting NKCC1 with Food Drug Administration (FDA)-approved diuretic bumetanide rescues inhibitory GABAergic transmission, synaptic plasticity, cognitive functions adult mice. Given that DS individuals mice show sleep disturbances, considering key role transmission sleep, we investigated whether upregulation contributes abnormalities Chronic oral administration ameliorated spectral profile architecture, electroencephalogram (EEG) entropy/complexity, accompanied by a lower hyperactivity trisomic These results offer potential avenue for addressing common disturbances DS.

Language: Английский

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Charged Interfaces in the Brain: How Electrostatic Forces May Guide Cerebrospinal Fluid Dynamics

European Journal of Neuroscience, Journal Year: 2025, Volume and Issue: 61(9)

Published: May 1, 2025

ABSTRACT Cerebrospinal fluid (CSF) flows play a main role in maintaining brain homeostasis, supporting waste clearance, nutrient delivery, and interstitial solute exchange. Although current models emphasize mechanical drivers like cardiac pulsation, respiration, ciliary motion, these mechanisms alone fall short of explaining the nuanced spatiotemporal regulation CSF flow observed under physiological pathological conditions—even when accounting for glymphatic framework. We hypothesize that electrostatic forces arising from charged cellular interfaces may contribute to movement through electro‐osmotic mechanisms. begin by examining biological basis surface charge brain, highlighting presence glycoproteins, ion channels, dynamic membrane potentials on ependymal/glial cells interfacing directly with pathways. Next, we describe key principles confined geometries, emphasizing how nanoscale charges can modulate motion without input. Drawing nanofluidic research, biophysics, electrohydrodynamic theory, argue conditions required coupling, i.e., ionic fluid, narrow conduits, patterned charge, are present within microenvironments. To test plausibility, computational simulations demonstrating patterns induce structured flow/solute transport, including nonlinear transitions oscillatory behaviors resemble rhythms. These findings support idea electrostatics modulatory regulation, complementing drivers. By integrating different disciplines, propose testable, mechanistically grounded hypothesis reframing dynamics as electrohydrodynamically sensitive processes. Our approach could inspire novel diagnostics/therapeutic strategies hydrocephalus neurodegenerative disease inform design targeted drug delivery systems.

Language: Английский

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Astrocytes facilitate gabazine‐evoked electrophysiological hyperactivity and distinct biochemical responses in mature neuronal cultures

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: July 13, 2024

Abstract Gamma‐aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in adult brain that binds to GABA receptors and hyperpolarizes postsynaptic neuron. Gabazine acts as a competitive antagonist type A (GABA R), thereby causing diminished neuronal hyperpolarization R‐mediated inhibition. However, biochemical effects potential regulatory role of astrocytes this process remain poorly understood. To address this, we investigated responses gabazine rat cortical cultures containing varying ratios neurons astrocytes. Electrophysiological characterization was performed utilizing microelectrode arrays (MEAs) with topologically controlled microcircuit enabled control network growth. Biochemical analysis using traditional dissociated on coverslips. Our study indicates that, upon stimulation, astrocyte‐rich exhibit elevated electrophysiological activity tyrosine phosphorylation tropomyosin receptor kinase B (TrkB; for brain‐derived neurotrophic factor), along distinct cytokine secretion profiles. Notably, lacking proper astrocytic support were found experience synapse loss decreased mitogen‐activated protein (MAPK) phosphorylation. Furthermore, contributed viability, morphology, vascular endothelial growth factor (VEGF) secretion, overall functionality, highlighting multifunctional image

Language: Английский

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All-optical reporting of inhibitory receptor driving force in the nervous system

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 16, 2024

Ionic driving forces provide the net electromotive force for ion movement across receptors, channels, and transporters, are a fundamental property of all cells. In nervous system, fast synaptic inhibition is mediated by chloride permeable GABAA glycine single-cell intracellular recordings have been only method estimating these receptors (DFGABAA). Here we present tool quantifying inhibitory receptor named ORCHID: all-Optical Reporting CHloride Ion Driving force. We demonstrate ORCHID's ability to accurate, high-throughput measurements resting dynamic DFGABAA from genetically targeted cell types over multiple timescales. ORCHID confirms theoretical predictions about biophysical mechanisms that establish DFGABAA, reveals differences in between neurons astrocytes, affords first vivo intact DFGABAA. This work extends our understanding transmission demonstrates potential all-optical methods assess ionic forces.

Language: Английский

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Ionic signalling (beyond calcium) in the nervous system: Physiology and Pathophysiology

Cell Calcium, Journal Year: 2024, Volume and Issue: 125, P. 102984 - 102984

Published: Dec. 7, 2024

Language: Английский

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