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Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive skeletal muscle degeneration and systemic effects, including the central nervous system (CNS). This study aimed to assess the impact of a 14-day ketogenic diet (DCet) on biochemical and clinical parameters in a DMD mouse model. Young adult mice (50 days old) were fed DCet, while control groups received a standard diet. On the 14th day, memory and behavior tests were conducted, followed by biochemical evaluations of oxidative stress, inflammatory biomarkers, body weight, feed intake, and brain-derived neurotrophic factor (BDNF) levels. mdx + DCet mice showed reduced mass (0.2 g ± 2.49) and improved memory retention (p < 0.05) compared to controls. Oxidative damage in muscle tissue and CNS decreased, along with a significant cytokine level reduction (p <0.05). The protocol led to an increase in hippocampal BDNF and mitochondrial respiratory complex activity in muscle tissue and the central nervous system (CNS), while also decreasing creatine kinase activity only in the striatum. Overall, a 14-day DCet showed protective effects by improving spatial learning and memory through reductions in oxidative stress and immune response, as well as increases in BDNF levels, consistent with our study's findings.
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INTRODUCTION: Congenital Muscular Dystrophy type 1D (MDC1D) is characterized by a hypoglycosylation of α-dystroglycan protein (α-DG), and this may be strongly implicated in increased skeletal muscle tissue degeneration and abnormal brain development, leading to cognitive impairment. However, the pathophysiology of brain involvement is still unclear. Low-intensity exercise training (LIET) is known to contribute to decreased muscle degeneration in animal models of other forms of progressive muscular dystrophies. AIM: The objective of this study was to analyze the effects of LIET on cognitive involvement and oxidative stress in brain tissue and gastrocnemius muscle. METHODS: Male homozygous (Largemyd-/-), heterozygous (Largemyd+/-), and wild-type mice were used. To complete 28 days of life, they were subjected to a low-intensity exercise training (LIET) for 8 weeks. After the last day of training, 24 h were expected when the animals were submitted to inhibitory avoidance and open-field test. The striatum, prefrontal cortex, hippocampus, cortex, and gastrocnemius were collected for evaluation of protein carbonylation, lipid peroxidation, and catalase and superoxide dismutase activity. RESULTS: LIET was observed to reverse the alteration in aversive and habituation memory. Increased protein carbonylation in the striatum, prefrontal cortex, and hippocampus and lipid peroxidation in the prefrontal cortex and hippocampus were also reversed by LIET. In the evaluation of the antioxidant activity, LIET increased catalase activity in the hippocampus and cortex. In the gastrocnemius, LIET decreased the protein carbonylation and lipid peroxidation and increased catalase and superoxide dismutase activity. CONCLUSION: In conclusion, it can be inferred that LIET for 8 weeks was able to reverse the cognitive damage and oxidative stress in brain tissue and gastrocnemius muscle in MDC1D animals.
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Encéfalo , Músculo Esquelético , Distrofias Musculares , Condicionamento Físico Animal , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Catalase , Deficiência Intelectual , Masculino , Camundongos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Distrofias Musculares/terapia , Estresse Oxidativo/fisiologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
At the end of 2019, a new disease with pandemic potential appeared in China. It was a novel coronavirus called coronavirus disease 2019 (COVID-19). Later, in the first quarter of 2020, the World Health Organization declared the outbreak of this disease a pandemic. Elderly people, people with comorbidities, and health care professionals are more vulnerable to COVID-19. Obesity has been growing exponentially worldwide, affecting several age groups. It is a morbidity that is associated with genetic, epigenetic, environment factors and/or interaction between them. Obesity is associated with the development of several diseases including diabetes mellitus, mainly type 2. Diabetes affects a significant portion of the global population. Obesity and diabetes are among the main risk factors for the development of severe symptoms of COVID-19, and individuals with these conditions constitute a risk group. Based on a literature review on obesity in people with diabetes in the framework of the COVID-19 pandemic, this study presents updated important considerations and care to be taken with this population.
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Duchenne muscular dystrophy (DMD) is a genetic disease associated with progressive skeletal muscle degeneration. In humans, DMD has an early onset, causes developmental delays, and is a devastating disease that drastically diminishes the quality of life of young individuals affected. The objective of this study was to evaluate the effects of a swimming protocol on memory and oxidative stress in an animal model of DMD. Male mdx and wild-type mice aged ≥ 28 days were used in this study. The animals were trained for a stepped swimming protocol for four consecutive weeks. The swimming protocol significantly reduced the levels of lipid peroxidation and protein carbonylation in the gastrocnemius, hippocampus, and striatum in the exercised animals. It also prevented lipid peroxidation in the diaphragm. Moreover, it increased the free thiol levels in the gastrocnemius, the diaphragm, and all central nervous system structures. The results showed that the protocol that applied swimming as a low-intensity aerobic exercise for 4 weeks prevented aversive memory and habituation in mdx mice.
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Antioxidantes/metabolismo , Memória/fisiologia , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/terapia , Condicionamento Físico Animal/fisiologia , Natação/fisiologia , Animais , Encéfalo/metabolismo , Masculino , Transtornos da Memória/genética , Transtornos da Memória/metabolismo , Transtornos da Memória/terapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/psicologia , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/psicologia , Natação/psicologiaRESUMO
OBJECTIVE: To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA). METHODS: To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements. RESULTS: It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1ß levels on 7, 14 and 45 postnatal days. CONCLUSION: This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.
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Animais Recém-Nascidos/psicologia , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Esquizofrenia/diagnóstico , Animais , Animais Recém-Nascidos/metabolismo , Escala de Avaliação Comportamental/normas , Encéfalo/metabolismo , Feminino , Idade Gestacional , Comportamento de Doença/fisiologia , Imunidade Ativa/efeitos dos fármacos , Inflamassomos/imunologia , Injeções Intraperitoneais , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mães , Transtornos Neurocognitivos/imunologia , Esquizofrenia/sangueRESUMO
Duchenne muscular dystrophy (DMD) is a condition caused by an amendment to the X chromosome, inherited as a recessive trait, and affects 1:3500 live births, especially males. Low-intensity exercise is known to decrease certain parameters associated with muscular degeneration in animal models of progressive muscular dystrophies. In the present study, 28-day-old male mdx and wild-type (wild) mice were used. The animals were subjected to a low-intensity physical exercise protocol for 8 weeks. It was found that this protocol was able to reduce oxidative stress in muscle tissue and in most of the CNS structures analyzed, with a significant increase in antioxidant activity in all analyzed structures. It is thus possible to infer that this exercise protocol was able to reduce oxidative stress and improve the energy metabolism in brain tissue and in the gastrocnemius muscle of animals with DMD.
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Terapia por Exercício/métodos , Distrofia Muscular de Duchenne/terapia , Condicionamento Físico Animal/métodos , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Estresse OxidativoRESUMO
BACKGROUND: Studies have shown the relationship between neuroinflammation and depressive- like parameters. However, research still has not been carried out to evaluate neuroinflammation in the neonatal period and psychiatric disorders in adulthood. OBJECTIVE: To verify the association between neonatal immune activation and depressive-like parameters in adulthood using an animal model. METHODS: Two days old C57BL/6 animals were exposed to lipopolysaccharides (LPS) or phosphate- buffered saline (PBS). When the animals were 46 days old, they received PBS or Imipramine at 14 days. At 60 days, the consumption of sucrose; immobility time; adrenal gland and the hippocampus weight; levels of plasma corticosterone and hippocampal Brain-derived neurotrophic factor (BDNF) were evaluated. RESULTS: It was observed that the animals exposed to LPS in the neonatal period and evaluated in adulthood decreased the consumption of sucrose and had reducted hippocampus weight. Also, the exposed animals presented an increase of immobility time, adrenal gland weight and plasma levels of corticosteroids. The use of imipramine did not only modify the decreased hippocampal weight. On the other hand, there were no alterations in the BDNF levels in the hippocampus with or without the use of imipramine. CONCLUSION: These results suggest that neonatal immune activation may be associated with depressive- like parameters in adulthood. It is believed that endotoxemia may trigger physiological and behavioral alterations, increasing vulnerability for the development of depression in adulthood.
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Depressão/tratamento farmacológico , Hipocampo/imunologia , Imipramina/farmacologia , Tempo , Animais , Animais Recém-Nascidos , Corticosterona/farmacologia , Depressão/induzido quimicamente , Depressão/imunologia , Transtorno Depressivo/induzido quimicamente , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/imunologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BLRESUMO
The neonatal immune system is still immature, which makes it more susceptible to the infectious agents. Neonatal immune activation is associated with increased permeability of the blood-brain barrier, causing an inflammatory cascade in the CNS and altering behavioral and neurochemical parameters. One of the hypotheses that has been studied is that neuroinflammation may be involved in neurodegenerative processes, such as Alzheimer's disease (AD). We evaluate visuospatial memory, cytokines levels, and the expression of tau and GSK-3ß proteins in hippocampus and cortex of animals exposed to neonatal endotoxemia. C57BL/6 mice aging two days received a single injection of subcutaneous lipopolysaccharide (LPS). At 60,120, and 180 days of age, visual-spatial memory was evaluated and the hippocampus and cortex were dissected to evaluate the cytokines levels and expression of tau and GSK-3ß proteins. The animals exposed to LPS in the neonatal period present with visuospatial memory impairment at 120 and 180 days of age. Here there was an increase of TNF-α and IL-1ß levels in the hippocampus and cortex only at 60 days of age. Here there was an increase in the expression of GSK-3ß in hippocampus of the animals at 60, 120, and 180 days of age. In the cortex, this increase occurred in the 120 and 180 days of age. Tau protein expression was high in hippocampus and cortex at 120 days of age and in hippocampus at 180 days of age. The data observed show that neonatal immune activation may be associated with visuospatial memory impairment, neuroinflammation, and increased expression of GSK-3ß and Tau proteins in the long term.
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Animais Recém-Nascidos/imunologia , Encéfalo/imunologia , Endotoxemia/imunologia , Inflamação/imunologia , Animais , Animais Recém-Nascidos/genética , Barreira Hematoencefálica/imunologia , Encéfalo/crescimento & desenvolvimento , Córtex Cerebelar/imunologia , Endotoxemia/induzido quimicamente , Glicogênio Sintase Quinase 3 beta/genética , Hipocampo/imunologia , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Lipopolissacarídeos/toxicidade , Camundongos , Proteínas tau/genéticaRESUMO
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that affects muscles and also the brain, resulting in memory and behavioral problems. In the pathogenesis of DMD, inflammation is an important factor during the degenerative process. However, the involvement of the brain is still unclear. Therefore, the objective of this study is to evaluate the cognitive involvement, BDNF levels, cytokine levels through the levels of TNF-α and IL-1ß, the myeloperoxidase (MPO) activity, and the expression of proteins postsynaptic density (PSD)-95 and synaptophysin in the brain of mdx mice. To this aim, we used adult mdx mice. It was observed that mdx mice presented deficits on the habituation, aversive, and object recognition memory. These animals also had a depression-like behavior and an anxiety-like behavior, a decrease of BDNF levels, an increase in the levels of TNF-α and IL-1ß, an increase of MPO activity, and an overexpression of synaptophysin and PSD-95 in brain tissue. In conclusion, these data show that mdx mice possibly present a neuroinflammatory component and the involvement of synaptic proteins associated to memory storage and restoring process impairment as well as a depressive- and anxiety-like behavior.