Untangling sex differences in glia-to-neuron communication in chronic alcohol exposure

Excessive alcohol consumption is global health challenge with profound neurobiological consequences. Our laboratory has shown that alcohol exposure induces reactive astrocytic changes, affecting gene expression, activity, and proliferation, while also altering microglial morphology and immune responses [1]. This study aims to characterise sex-specific effects of chronic alcohol consumption on the prefrontal cortex (PFC), focusing on glial cell morphology, synaptic density, and behaviour. Adult mice underwent a voluntary drinking model using an intermittent ‘every-other-day’ (EOD) paradigm with 15% (v/v) ethanol for three weeks. Behavioural tests for anxiety, depression, and memory were conducted before sacrifice. Brains were processed for glial cell analysis using immunohistochemistry and confocal microscopy. Synaptosomes were isolated for proteomics and analysis used STRING and Panther. Preliminary data reveal sex-dependent glial and synaptic adaptations. Males showed increased astrocyte volume in the ventromedial PFC (vmPFC) and hyper-ramification in the ventrolateral PFC (vlPFC), while females showed reductions in astrocyte size and complexity. Microglia also displayed sex-specific changes: males had decreased microglial volume in the vlPFC, while females exhibited increased microglial size. Inhibitory synapse density was elevated in males, while females showed an increase in excitatory synapses. These changes correlated with behavioural differences—males displayed heightened anxiety, whereas females exhibited reduced anxiety. Proteomic analysis further supports sex-dependent molecular adaptations: male-enriched proteins were linked to myelination and glial development, while female-specific proteins were associated with mRNA processing, RNA transport, and axonogenesis. Chronic alcohol exposure induces sex-specific neuroimmune and synaptic alterations, potentially contributing to differential susceptibility to alcohol use disorders (AUD).

Keywords

Neuroimmune response Glial activation Alcohol-related neuroplasticity PFC Dysfunction Sex differences

URI

http://hdl.handle.net/10400.22/30848

Citation

Pacheco, R., Canedo, T., Rodrigues, A. M., Moreira, J., Relvas, J. B., Vieira, C. P., Socodato, R., & Sumavielle, T. (2025). Untangling sex differences in glia-to-neuron communication in chronic alcohol exposure. Livro de Resumos do 18º Encontro de Investigação Jovem da U.Porto, 999–1000. https://www.up.pt/ijup/wp-content/uploads/sites/892/2025/06/Livro-de-Resumos_IJUP-2025.pdf

Publisher

Universidade do Porto

Collections

ESS - CF - Posters apresentados em eventos científicos

CC License

Without CC licence

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