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Cited by 23Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsConnexins and lens biology

On astrocyte-neuron interactions: broad insights from the striatum

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Khakh, Baljit S.·2025·Neuron
DOI 10.1016/j.neuron.2025.08.009PMC PMC12571388
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Abstract

A long-standing question in biology and medicine concerns how astrocytes influence neurons. Here, progress concerning how astrocytes affect neurons and neural circuits is summarized by focusing on data and concepts from studies of the striatum, which has emerged as a model nucleus. Mechanisms broadly applicable across brain regions and disorders are emphasized, and knowledge gaps are described. Experiments spanning multiple scales of biology show that astrocytes regulate neural circuits by virtue of homeostatic signaling and through astrocyte-neuron interactions. During disease, astrocytes contribute to nervous system malfunction in context-specific ways through failures of normal functions and the development of maladaptive responses. As ideally positioned endogenous cellular neuromodulators, astrocytes can be targeted for strategies to regulate neural circuits in brain disorders. After a historically slow start for the field, astrocyte-neuron interactions are now recognized as consequential for physiology and behavior, critically involved in pathophysiology, and exploitable in disease.

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  • When driven into a reactive state by EDC-associated inflammation and oxidative stress, astrocytes can lose these homeostatic functions and instead sustain chronic inflammatory signaling, impair neurotransmitter clearance, and weaken neuronal metabolic support.

    “When driven into a reactive state by EDC-associated inflammation and oxidative stress, however, astrocytes can lose these homeostatic functions and instead sustain chronic inflammatory signaling, impair neurotransmitter clearance, and weaken neuronal metabolic support (Calì et al., 2024; Khakh, 2025; Rupareliya et al., 2023).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Khakh, 2025

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  • Under physiological conditions, astrocytes maintain BBB function, regulate extracellular ion balance, recycle neurotransmitters such as glutamate, provide metabolic support to neurons, and participate in synapse formation and elimination.

    “Under physiological conditions, they maintain BBB function, regulate extracellular ion balance, recycle neurotransmitters such as glutamate, provide metabolic support to neurons, and participate in synapse formation and elimination.”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Khakh, 2025

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Cited by

Sorted by citations

Authors
Khakh, B. S.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Khakh, Baljit S.
ORCID
Khakh, Baljit S.
Venue
Neuron
Publisher
Elsevier BV
Published
2025-10
Volume
113
Issue
19
Pages
3079-3107
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2025.08.009
PMC
PMC12571388
OpenAlex
W4414343565
Cited by
23
References
28
Citations by year
2026: 18 · 2025: 5
FWCI
2.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by)
Funders
  • National Institutes of Health (NS111583, MH134926, AG075955)
  • University of California
  • CHDI Foundation Los Angeles
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords
astrocyte-neuron interaction, striatum, astrocytes, neural circuits, astrocyte dysfunction, neuromodulation, brain disorders, neurodegeneration
MeSH terms
Animals, Astrocytes, Cell Communication, Corpus Striatum, Humans, Neurons

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