Browsing by Author "Rodrigues, Ana Margarida"
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- Deciphering the astrocytic and synaptic changes under chronic alcohol exposure using a self-administration paradigmPublication . Rodrigues, Ana Margarida; Canedo, Teresa; Terceiro, Ana Filipa; Tedim-Moreira, Joana; Silva, Ana Isabel; Magalhães, Ana; Relvas, João; Summavielle, TeresaDrug abuse is characterized by a compulsive and persistent drug-seeking behaviour, despite the harmful emotional, physical and social consequences. Our laboratory has previously found that the neuronal-glial crosstalk is critical in relaying the changes caused by acute exposure to psychoactive drugs through neuroimmune mechanisms. We have also reported that microglia can engulf postsynaptic components in the prefrontal cortex (PFC) of mice after repeated alcohol exposure and this led to increased anxiety in mice. The adverse effects of alcohol on the central nervous system (CNS) are well described, with astrocytes becoming reactive and displaying changes in gene expression, activity and proliferation. However, the mechanisms involved are not yet fully understood. We are currently characterizing the astrocytic response under chronic alcohol consumption, taking into account the crucial interaction between neuronal and glial cells in the development and maintenance of addiction. Using a well-established voluntary alcohol drinking paradigm, we are evaluating alcohol-associated changes in PFC astrocytes, synapses and their behavioural correlates. Our preliminary results indicate similar alcohol consumption patterns between males and females, however, males, but not females, present altered weight gain and experience a significant increase in inhibitory synapse density after chronic exposure to ethanol when compared to the control group. Our work is contributing to a better understanding of the impact of chronic alcohol intake and may lead to the development of new strategies for pharmacological intervention in drug addiction, based on the targets identified as critical for the neuronal-glial crosstalk.
- Untangling sex differences in glia-to-neuron communication in chronic alcohol exposurePublication . Pacheco, Raquel; Canedo, Teresa; Rodrigues, Ana Margarida; Moreira, Joana; Relvas, João B.; Vieira, Cristina P.; Socodato, Renato; Sumavielle, Teresa; Summavielle, TeresaExcessive 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).