Astrocyte- and Microglia-Derived Factors in Neuroinflammation: Impact on Neuronal and Synaptic Structure and Function

Giuliana Colonna Soldavini^1,2,#, María Belén Gomez^1,#, Jeremias Martin Cuello^1,2, Martín Gabriel Codagnone^1,2, Analía Gabriela Reinés^1,2,*
1 Facultad de Medicina, Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis” (IBCN), Universidad de Buenos Aires-CONICET, Calle Paraguay 2155 3er piso, Ciudad de Buenos Aires, Argentina
2 Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 5to piso, Ciudad de Buenos Aires, Argentina
* Corresponding Author: Analía Gabriela Reinés. Email: email
# These authors contributed equally to this work

BIOCELL https://doi.org/10.32604/biocell.2026.082340

Received 14 March 2026; Accepted 05 June 2026; Published online 29 June 2026

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Abstract

Astrocytes and microglia are key regulators of neuronal and synaptic function through dynamic interactions with neurons and with each other. Under pathological conditions, these interactions become dysregulated, promoting reactive glial states characterized by the release of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6, as well as complement components such as C1q and C3, reactive oxygen species, and other inflammatory mediators that disrupt synaptic homeostasis and neuronal stability. In this review, we examine the molecular and cellular mechanisms underlying neuron-glia and astrocyte-microglia communication in physiological and neuroinflammatory conditions. We discuss how glial-derived factors influence synaptic remodeling, excitotoxicity, altered plasticity, and neuronal function, highlighting their contribution to neuroinflammation and synaptic dysfunction. Finally, we explore therapeutic strategies aimed at modulating glial reactivity and restoring synaptic homeostasis to limit neuronal damage and neurodegeneration.