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Efeito da pré-exposição ao etanol na reatividade microglial induzida pela proteína spike de SARS-CoV2

Wed, 01 Jan 2025 00:00:00 GMT

Title: Efeito da pré-exposição ao etanol na reatividade microglial induzida pela proteína spike de SARS-CoV2 Author(s)/Inventor(s): Vieira, Beatriz Esteves Advisor: Silva, Joice Stipursky Abstract: COVID-19, caused by the coronavirus, SARS-CoV-2, has caused more than 700 million confirmed cases according to the World Health Organization (WHO). Along with life threatening symptoms, WHO also recognized, during the peak of the pandemic, an increase in alcoholic beverages consumption by population in different countries, reported as way to deal with depression and anxiety resulting from social isolation. In the Central Nervous System (CNS), microglial cells control the immune response by mediating neuroinflammation. It is known that alcohol consumption leads to neuroinflammation and neurodegeneration in CNS. In the context of COVID19, neuroinflammation and glial reactivity are events mediated by the infection of human glial cells by SARS-CoV2, which recognizes, through its Spike-1 surface protein, the angiotensin-converting enzyme-2 (ACE-2) and other proteins such as TMPRSS2 and TLR4. Although different risk factors for COVID-19 have been described, it is not known whether alcohol consumption could represent a risk factor for SARS-CoV2-induced microglial reactivity. In this study, murine microglial cultures (BV-2) were treated with ethanol (170mM or 340mM) acute for 24h or chronically (1 treatment per day/72hs), and then exposed to the Spike1 protein (1μg/ml) for 24h. We observed by immunofluorescence that the ethanol treatment increases the levels of ACE2 by 1.2x, compared to the control. When analyzing markers of microglial reactivity, only spike-1 treated cells showed an increase in C3 expression levels, an event that was prevented by previous chronic treatment with ethanol. The chronic treatment alone or exposure to spike-1 alone appears to increase the levels of IL-1β and CD-86, an event that was lost by the spike-1 treatment in cells previously exposed to ethanol. Ethanol treatment alone did not induce phagocytic activity, an event that is only observed by Spike treatment in cells previously exposed to ethanol. In vivo, ethanol appeared to induce microglial reactivity by increasing IBA1 levels in the cerebral cortex and altered the expression of ACE-2, TMPRSS2 and TLR4 in the CNS in a region-specific manner. Human cortical microglia showed levels of expression of ACE-2, TLR4, CD-11b and IBA-1 induced by ethanol in a dosedependent manner. These data suggest that exposure to ethanol appears to reduce the microglial response to Spike-1, which could contribute to the loss of microglial function in controlling the immune response and neuroinflammation in the CNS. Publisher: Universidade Federal do Rio de Janeiro Type: Dissertação

Análise do secretoma das células de carcinoma mamário silenciadas para galectina-3

Tue, 17 Jun 2025 00:00:00 GMT

Title: Análise do secretoma das células de carcinoma mamário silenciadas para galectina-3 Author(s)/Inventor(s): Rosa, Evelyn Emyli Barros Advisor: El-Cheikh, Márcia Cury Abstract: Breast cancer has a high incidence among women and remains one of the major global public health challenges. Galectin-3, a multifunctional lectin with affinity for β-galactosides, plays a role in breast tumors due to its ability to mediate cell–cell and cell–extracellular matrix interactions. Therefore, this study aimed to investigate the impact of Galectin-3 silencing in 4T1 murine breast carcinoma cells by analyzing their secretome in comparison to control cells. The results indicate that Galectin-3 silencing led to increased cell migration and changes in adhesion molecules such as versican, suggesting a modulatory role in tumor biology. Proteins with reduced expression in the silenced lineage were associated with hexose and glucose metabolism, showing strong interactions with Eno1, AldoA, AldoC, and GAPDH, which are key enzymes in glycolysis and gluconeogenesis. In contrast, proteins such as MMP3, MMP10, THBS1, and DAG-1 were upregulated, indicating potential involvement in extracellular matrix remodeling and metastatic progression. These findings demonstrate, for the first time, that Galectin-3 silencing significantly alters the secretome of 4T1 cells, promoting metastatic features, as evidenced by both in vitro and in vivo assays. Publisher: Universidade Federal do Rio de Janeiro Type: Dissertação

Mudanças comportamentais e alterações de espessura cortical em longo prazo em mulheres com fibromialgia

Mon, 06 Oct 2025 00:00:00 GMT

Title: Mudanças comportamentais e alterações de espessura cortical em longo prazo em mulheres com fibromialgia Author(s)/Inventor(s): Oliveira Neto, Paulo Gomes de Advisor: Santos, Marcos Fabio Henriques dos Abstract: Introduction: Fibromyalgia is a chronic pain syndrome of central origin, characterized by widespread musculoskeletal pain, fatigue, cognitive alterations, and sleep disturbances. Classified as a nociplastic condition, the syndrome does not result from inflammatory processes or structural lesions, but rather from dysfunctions in central pain modulation mechanisms. In addition, studies indicate that emotional and cognitive factors, such as attention, motivation, and catastrophizing, modulate the pain experience in these patients. Objectives: The aim of this study was to examine long-term brain and behavioral alterations in patients with fibromyalgia (FM) compared to healthy individuals. Methods: Data from 33 female volunteers with FM and 33 age- and education-matched healthy women were analyzed to assess cortical thickness using high-resolution T1-weighted magnetic resonance imaging (MRI) acquired on a 3T scanner. Furthermore, the Toronto Alexithymia Scale, the Positive and Negative Affect Schedule (PANAS), the Emotion Regulation Questionnaire (ERQ), and the Hamilton Depression and Anxiety Rating Scales were used to evaluate behavioral alterations. Results: The findings indicated significant differences in cortical structure in the right cerebral hemisphere between groups, specifically in the anterior insular cortex, precentral gyrus, and postcentral gyrus (p<0.001). No differences were found in the left hemisphere. The FM group scored higher in alexithymia (p<0.01), negative affect (p<0.01), anxiety symptoms (p<0.01), and depression (p<0.01), and lower in positive affect (p<0.01). Moreover, a negative correlation was observed between the right anterior insular cortex and the Toronto Alexithymia Scale (p<0.001). Conclusion: This study demonstrated long-term brain and behavioral alterations in FM patients, suggesting notable neurophysiological changes associated with this chronic pain condition. The study provides new insights into how FM may affect brain health and highlights potential biomarkers for the condition. Publisher: Universidade Federal do Rio de Janeiro Type: Dissertação

Interneurônios inibitórios do neocórtex e sua relação com a epileptogênese frente à exposição pré-natal ao álcool

Fri, 01 Aug 2025 00:00:00 GMT

Title: Interneurônios inibitórios do neocórtex e sua relação com a epileptogênese frente à exposição pré-natal ao álcool Author(s)/Inventor(s): Azevedo, Thamyres Bastos de Advisor: Mendonça, Henrique Rocha Abstract: Prenatal alcohol exposure (PAE) is considered a risk factor that can lead to alterations in the development of the central nervous system, such as structural and functional changes, including epileptogenesis. This study aimed to investigate the effects of PAE on cortical excitability and inhibitory interneurons in the neocortex of mice, focusing on the Parvalbumin+, Somatostatin+, and Vasoactive Intestinal Peptide (VIP)+ subtypes. Pregnant Swiss mice were subjected to oral administration of ethanol (3.0 g/kg, 30% v/v) from gestational day 14 to 19. On postnatal day 16 (PND16), the offspring were evaluated for susceptibility to febrile and pentylenetetrazol (PTZ)-induced seizures, as well as for brain morphology and immunofluorescence analysis to identify interneurons. The results showed that PAE did not cause significant changes in cortical thickness or length. However, an increased duration of stage 6 of the PTZ-induced seizure was observed in ethanolexposed animals, as well as a longer latency to febrile seizures. Immunolabeling revealed an increased density of Parvalbumin+ interneurons in the supragranular layers of the cortex, with no significant changes in the Somatostatin+ and VIP+ populations. These findings suggest that PAE alters the distribution of interneurons, impacting the regulation of cortical excitability and possibly contributing to the increased susceptibility to epileptogenesis observed in fetal alcohol spectrum disorder. Publisher: Universidade Federal do Rio de Janeiro Type: Dissertação