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Obesity is a significant health concern that is correlated with various adverse health outcomes. Diet-induced obesity (DIO) is associated with impaired cognitive function. Pharmacological treatments for obesity are limited and may have serious adverse effects. Zingiber officinale (ZO) has anti-inflammatory and antioxidant effects, in addition to metabolic effects. This study aimed to assess the effects of Zingiber officinale supplementation on cognitive function, anxiety levels, neurotrophin levels, and the inflammatory and oxidative status in the cortex following DIO in mice. Two-month-old male Swiss mice were fed DIO or standard chow for 4 months and subsequently subdivided into the following groups (n = 10 mice/group): (i) control - vehicle (CNT + vehicle); (ii) CNT supplemented with ZO (CNT + ZO); (iii) obese mice (DIO + vehicle); and (iv) obese mice supplemented with ZO (DIO + ZO) (n = 10). Zingiber officinale extract (400 mg/kg/day) was administered for 35 days via oral gavage. The DIO + vehicle group exhibited impaired recognition memory. The CNT + ZO group presented a greater number of crossings in the open field. No difference between the groups was observed in the plus maze test. DIO + vehicle increased the DCFH and carbonylation levels in the cortex. The DIO + vehicle group presented a reduction in catalase activity. The expression of inflammatory or neurotrophin markers in the cerebral cortex was not different. In conclusion, our findings indicate that supplementation with ZO reverses the cognitive impairment in DIO mice and enhances the antioxidant status of the cerebral cortex.

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The accumulation of oxidized low-density lipoprotein (oxLDL) and its toxicity in the arterial wall have been implicated in atherosclerosis. This study aimed to investigate the mechanisms underlying the atheroprotective effect of bixin, a carotenoid obtained from the seeds of the tropical plant Bixa orellana, on Cu2+-induced LDL oxidation and oxLDL-mediated effects in J774A.1 macrophage cells. Bixin's effects were compared to those of lycopene, a carotenoid widely studied for its cardiovascular protective effects. LDL was isolated from human plasma, incubated with bixin or lycopene (positive control), and subjected to oxidation with CuSO4. Afterward, bixin or lycopene was incubated with J774A.1 macrophage cells and exposed to oxLDL. The levels of ROS, RNS, GSH, nitrite, mitochondrial function, and foam cell formation, as well as the expression of proteins related to the antioxidant and inflammatory status, were evaluated. The effect of bixin in inhibiting in vitro human-isolated LDL oxidation was more potent (5-6-fold) than that of lycopene. Bixin pretreatment reduced the atherogenic signaling triggered by oxLDL in the macrophages, namely the generation of reactive species, disturbance of nitric oxide homeostasis, mitochondrial dysfunction, and foam cell formation. The cytoprotective effects of bixin were accompanied by the upregulation of Nrf2 and the downregulation of the NF-kB pathways. Lycopene showed the same protective effect as bixin, except that it did not prevent mitochondrial dysfunction. The efficient performance of bixin makes it an ideal candidate for further trials as a new nutraceutical compound for the prevention of atherosclerosis.

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Major Depressive Disorder (MDD) is a severe and multifactorial psychiatric condition. Evidence has shown that environmental factors, such as stress, significantly explain MDD pathophysiology. Studies have hypothesized that changes in histone methylation patterns are involved in impaired glutamatergic signaling. Based on this scenario, this study aims to investigate histone 3 involvement in depression susceptibility or resilience in MDD pathophysiology by investigating cellular and molecular parameters related to i) glutamatergic neurotransmission, ii) astrocytic functioning, and iii) neurogenesis. For this, we subjected male Wistar rats to the Chronic Unpredictable Mild Stress (CUMS) model of depression. We propose that by evaluating the sucrose consumption, open field, and object recognition test performance from animals submitted to CUMS, it is possible to predict with high specificity rats with susceptibility to depressive-like phenotype and resilient to the depressive-like phenotype. We also demonstrated, for the first time, that patterns of H3K4me3, H3K9me3, H3K27me3, and H3K36me3 trimethylation are strictly associated with the resilient or susceptible to depressive-like phenotype in a brain-region-specific manner. Additionally, susceptible animals have reduced DCx and GFAP and resilient animals present increase of AQP-4 immunoreactivity. Together, these results provide evidence that H3 trimethylations are related to the development of the resilient or susceptible to depressive-like phenotype, contributing to further advances in the pathophysiology of MDD and the discovery of mechanisms behind resilience.

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RESUMO Objetivo: Avaliar o impacto da pandemia da COVID-19 nas doações de córnea e na atuação de um banco de olhos na região da Zona da Mata Mineira. Métodos: Análise retrospectiva de prontuários de todas as doações obtidas pelo Banco de Olhos Hospital Regional Dr. João Penido, de Juiz de Fora (MG), entre 2017 e 2022, comparando-se os períodos pré (janeiro de 2017 a 11 de março de 2020) e pós-pandemia (12 de março de 2020 a dezembro de 2022). Resultados: Verificou-se uma redução nas doações de córnea e no número de tecidos corneanos liberados para transplantes no período pós pandemia, 68,2 e 67,3% respectivamente. Não houve diferença estatística no sexo, idade média, causa básica de óbito dos doadores, nos números de globos oculares não preservados e de córneas não preservadas entre os períodos pré e pós-pandemia. As taxas de liberação de córneas preservadas e aproveitamento das doações foram maiores no período pós-pandemia: 86,5 versus 79,0% e 68,1 versus 63,0%, respectivamente. O número de tecidos corneanos liberados para transplantes óptico e tectônico foram estatisticamente maiores no período pré-pandemia (p<0,001). Conclusão: A pandemia da COVID-19 impactou negativamente nas doações de córnea e na atuação do banco de olhos na região da Zona da Mata Mineira.

ABSTRACT Objective: To assess the impact of the COVID-19 pandemic on corneal donations and the operation of the eye bank in the Zona da Mata Mineira Region. Methods: Retrospective analysis of medical records of all donations obtained by the Banco de Olhos Hospital Regional Dr. João Penido/FHEMIG, Juiz de Fora - MG between 2017 and 2022, comparing pre (January/2017 - March 11/2020) and post-pandemic (12/March/2020 - December/2022) periods. Results: There was a reduction in cornea donations and the number of corneal tissues released for transplants in the post-pandemic period, 68.2% and 67.3%, respectively. There was no statistical difference in gender, average age, basic cause of death of donors, in the number of non-preserved eyeballs and non-preserved corneas between the pre- and post-pandemic periods. The rates of release of preserved corneas and use of donations were higher in the post-pandemic period, 86.5% vs 79.0%, and 68.1% vs 63.0%, respectively. The number of corneal tissues released for optical and tectonic transplants were statistically higher in the pre-pandemic period (P<0.001). Conclusion: The COVID-19 pandemic had a negative impact on cornea donations and the eye bank's operations in the Zona da Mata Mineira region.

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Inflammatory bowel diseases (IBD) cause increased inflammatory signalling and oxidative damage. IBDs are correlated with an increased incidence of brain-related disorders suggesting that the gut-brain-axis exerts a pivotal role in IBD. Butyrate is one of the main microbial metabolites in the colon, and it can cross the blood-brain barrier, directly affecting the brain. We induced ulcerative colitis (UC) in mice utilizing dextran sodium sulfate (DSS) in the drinking water for 7 days. Animals were divided into four groups, receiving water or DSS and treated with saline or 0,066 g/kg of Sodium Butyrate for 7 days. We also used an integrative approach, combining bioinformatics functional network and experimental strategies to understand how butyrate may affect UC. Butyrate was able to attenuate colitis severity and intestinal inflammation. Butyrate protected the colon against oxidative damage in UC and protected the prefrontal cortex from neuroinflammation observed in DSS group. Immunocontent of tight junction proteins Claudin-5 and Occludin were reduced in colon of DSS group mice and butyrate was able to restore to control levels. Occludin and Claudin-5 decrease in DSS group indicate that an intestinal barrier disruption may lead to the increased influx of gut-derived molecules, causing neuroinflammation in the prefrontal cortex, observed by increased IBA-1 marker. The probable protection mechanism of butyrate treatment occurs through NRF2 through Nrf2 and HIF-1α activation and consequent activation of catalase and superoxide dismutase. Our data suggest that systemic inflammation associated with intestinal barrier disruption in UC leads to neuroinflammation in the prefrontal cortex, which was atenuated by butyrate.

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Familial hypercholesterolemia (FH) is caused by mutations in the gene that encodes the low-density lipoprotein (LDL) receptor, which leads to an excessive increase in plasma LDL cholesterol levels. Previous studies have shown that FH is associated with gliosis, blood-brain barrier dysfunction, and memory impairment, but the mechanisms associated with these events are still not fully understood. Therefore, we aimed to investigate the role of microgliosis in the neurochemical and behavioral changes associated with FH using LDL receptor knockout (LDLr-/- ) mice. We noticed that microgliosis was more severe in the hippocampus of middle-aged LDLr-/- mice, which was accompanied by microglial morphological changes and alterations in the immunocontent of synaptic protein markers. At three months of age, the LDLr-/- mice already showed increased microgliosis and decreased immunocontent of claudin-5 in the prefrontal cortex (PFC). Subsequently, 6-month-old male C57BL/6 wild-type and LDLr-/- mice were treated once daily for 30 days with minocycline (a pharmacological inhibitor of microglial cell reactivity) or vehicle (saline). Adult LDLr-/- mice displayed significant hippocampal memory impairment, which was ameliorated by minocycline treatment. Non-treated LDLr-/- mice showed increased microglial density in all hippocampal regions analyzed, a process that was not altered by minocycline treatment. Region-specific microglial morphological analysis revealed different effects of genotype or minocycline treatment on microglial morphology, depending on the hippocampal subregion analyzed. Moreover, 6-month-old LDLr-/- mice exhibited a slight but not significant increase in IBA-1 immunoreactivity in the PFC, which was reduced by minocycline treatment without altering microglial morphology. Minocycline treatment also reduced the presence of microglia within the perivascular area in both the PFC and hippocampus of LDLr-/- mice. However, no significant effects of either genotype or minocycline treatment were observed regarding the phagocytic activity of microglia in the PFC and hippocampus. Our results demonstrate that hippocampal microgliosis, microglial morphological changes, and the presence of these glial cells in the perivascular area, but not increased microglial phagocytic activity, are associated with cognitive deficits in a mouse model of FH.

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a persistent impairment of social skills, including aspects of perception, interpretation, and response, combined with restricted and repetitive behavior. ASD is a complex and multifactorial condition, and its etiology could be attributed to genetic and environmental factors. Despite numerous clinical and experimental studies, no etiological factor, biomarker, and specific model of transmission have been consistently associated with ASD. However, an imbalance in cholesterol levels has been observed in many patients, more specifically, a condition of hypocholesterolemia, which seems to be shared between ASD and ASD-related genetic syndromes such as fragile X syndrome (FXS), Rett syndrome (RS), and Smith- Lemli-Opitz (SLO). Furthermore, it is known that alterations in cholesterol levels lead to neuroinflammation, oxidative stress, impaired myelination and synaptogenesis. Thus, the aim of this review is to discuss the cholesterol metabolic pathways in the ASD context, as well as in genetic syndromes related to ASD, through clinical observations and animal models. In fact, SLO, FXS, and RS patients display early behavioral markers of ASD followed by cholesterol disturbances. Several studies have demonstrated the role of cholesterol in psychiatric conditions and how its levels modulate brain neurodevelopment. This review suggests an important relationship between ASD pathology and cholesterol metabolism impairment; thus, some strategies could be raised - at clinical and pre-clinical levels - to explore whether cholesterol metabolism disturbance has a generally adverse effect in exacerbating the symptoms of ASD patients.

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Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we reported the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We now demonstrate that the striatum rules the ergogenic effects of caffeine through neuroplasticity changes. Thirty-four Swiss (8-10 weeks, 47 ± 1.5 g) and twenty-four C57BL/6J (8-10 weeks, 23.9 ± 0.4 g) adult male mice were studied behaviorly and electrophysiologically using caffeine and energy metabolism was studied in SH-SY5Y cells. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 µg) caffeine was psychostimulant in the open field (p < 0.05) and increased grip efficiency (p < 0.05). Caffeine also shifted long-term depression (LTD) to potentiation (LTP) in striatal slices and increased the mitochondrial mass (p < 0.05) and membrane potential (p < 0.05) in SH-SY5Y dopaminergic cells. Our results demonstrate the role of the striatum in the ergogenic effects of caffeine, with changes in neuroplasticity and mitochondrial metabolism.

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Women older than 60 have a higher risk of dementia, aging-related cognitive decline, and Alzheimer's Disease (AD) than the rest of the population. The main reason is hormonal senescence after menopause, a period characterized by a decline in estrogen levels. Since the effectiveness of drugs currently approved for the treatment of AD is limited, it is necessary to seek the development of new therapeutic strategies. Vitamin D deficiency is prevalent in AD patients and individuals with dementia in general. The supplementation of this vitamin in dementia patients might be an interesting approach for increasing the effectiveness of pre-existing medications for dementia treatment. Thus, the present study aims to investigate the effect of vitamin D treatment associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for five months and subjected to a dementia animal model induced by intracerebroventricular injection of aggregated amyloid ßeta (Aß1-42). For this purpose, Balb/c mice were divided into five experimental groups, which received 17 days of combined therapy with vitamin D, donepezil, and memantine. Then, animals were subjected to behavioral tests. OVX groups exhibited reduced levels of estradiol (E2) in serum, which was not altered by the combined therapy. Higher levels of vitamin D3 were found in the OVX animals submitted to the triple-association treatment. Mice exposed to both OVX and the dementia animal model presented impairment in short and long-term spatial and habituation memories. Also, female mice exposed to Aß and OVX exhibited a reduction in brain-derived neurotrophic factor (BDNF) and interleukin-4 (IL-4) levels, and an increase in tumor necrose factor-α (TNFα) levels in the hippocampus. Besides, increased levels of IL-1ß in the hippocampus and cerebral cortex were observed, as well as a significant increase in immunoreactivity for glial fibrillary acidic protein (GFAP), an astrocytes marker, in the hippocampus. Notably, triple-association treatment reversed the effects of the exposition of mice to Aß and OVX in the long-term spatial and habituation memories impairment, as well as reversed changes in TNFα, IL-1ß, IL-4, and GFAP immunoreactivity levels in the hippocampus of treated animals. Our results indicate that the therapeutic association of vitamin D, memantine, and donepezil has beneficial effects on memory performance and attenuated the neuroinflammatory response in female mice subjected to OVX associated with a dementia animal model.

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Nanotechnology is an emerging and expanding technology worldwide. The manipulation of materials on a nanometric scale generates new products with unique properties called nanomaterials. Due to its significant expansion, nanotechnology has been applied in several fields of study, including developing materials for biomedical applications, i.e., nanomedicine. The use of nanomaterials, including nanoparticles, in nanomedicine, is promising and has been associated with pharmacokinetics, bioavailability, and therapeutic advantages. In this regard, it is worth mentioning the Gold Nanoparticles (AuNPs). AuNPs' biomedical application is extensively investigated due to their high biocompatibility, simple preparation, catalytic, and redox properties. Experimental studies have pointed out critical therapeutic actions related to AuNPs in different pathophysiological contexts, mainly due to their anti-inflammatory and antioxidant effects. Thus, in this review, we will discuss the main experimental findings related to the therapeutic properties of AuNPs in metabolic, neurodegenerative diseases, and ultimately brain dysfunctions related to metabolic diseases.

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