Browsing by Author "Moreira, Joana"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Deciphering neuroimmune interactions in alcohol intake in mouse model of intermittent access in male and femalePublication . Pacheco, Raquel; Canedo, Teresa; Rodrigues, Ana M.; Moreira, Joana; Relvas, João B.; Socodato, Renato; Summavielle, Teresa; Summavielle, TeresaExcessive alcohol consumption continues to pose a significant global health challenge, with detrimental effects on millions of individuals. Our laboratory has shown that alcohol exposure triggers reactive changes in astrocytes, including alterations in gene expression, activity, and proliferation, while also affecting microglial morphology and immune responses. We are to characterizing the effects of chronic alcohol consumption using a wellestablished voluntary alcohol drinking model in adult mice, to investigate the impact of chronic alcohol exposure on the prefrontal cortex (PFC), focusing on glial cell morphology, synaptic density, and behaviour. Mice are exposed to intermittent “every-other-day” (EOD) access to alcohol 15% (v/v) for 3 weeks, and behaviourally tested for anxiety, depression and memory, before sacrifice at 21 days of alcohol, or at 7 days of withdrawal. Brains were processed for glial cell analysis. Our preliminary findings revealed sex-specific responses following chronic alcohol exposure. Male mice exhibited increased astrocyte volume in the ventromedial PFC (vmPFC) and hyper-ramification in the ventrolateral PFC (vlPFC), whereas females displayed reductions in astrocyte size and complexity. Microglia morphology also differed between sexes, with females showing increased cell volume and males displaying reduced microglial volume in the vlPFC. These results suggest distinctive immune and synaptic responses to ethanol in males and females. Of note, we observed heightened inhibitory synapse density in the male PFC, while females exhibited increased excitatory synapse density. We are now conducting a proteomic analysis of PFC synaptosomes to identify important molecular targets in the crosstalk between neuros and glial cells. With this work we expect to clarify the complex interplay between chronic ethanol exposure, sex, and PFC function, find also new targets for innovative therapeutic approaches.
- Norhierridin B, a New Hierridin B-Based Hydroquinone with Improved Antiproliferative ActivityPublication . Brandão, Pedro; Moreira, Joana; Almeida, Joana; Nazareth, Nair; Sampaio-Dias, Ivo E.; Vasconcelos, Vítor; Martins, Rosario; Leão, Pedro; Pinto, Madalena; Saraíva, Lucília; Cidade, HonorinaHierridin B (6), a methylated hydroquinone isolated from the marine picocyanobacterium Cyanobium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (10), as well as its structurally-related quinone (9), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B (10) showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound 10 on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B (10) interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone 10 when compared to 6 and its structurally-related quinone (9). Notably, hydroquinone 10 displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance.
- 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).