RESUMO
Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer's disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels in the plasma of choline-treated APP/PS1 mice (an AD mouse model) with and without probiotic treatments. We found that declines in L.plantarum in the gut were associated with cognitive impairment. Moreover, 12-weeks of treatment with memantine plus L. plantarum ameliorated cognitive deterioration, decreased Αß levels in the hippocampus, and protected neuronal integrity and plasticity. These effects were accompanied by reductions in TMAO synthesis and neuroinflammation. These experiments demonstrate that L. plantarum augments the beneficial therapeutic effects of memantine treatment in APP/PS1 mice by remodeling the intestinal microbiota, inhibiting the synthesis of TMAO, and reducing clusterin levels. Our results thus highlight intestinal microbiota as a potential therapeutic target to decrease the risk of AD.
Assuntos
Doença de Alzheimer/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Lactobacillus plantarum , Memantina/farmacologia , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Animais , Animais Geneticamente Modificados , Biomarcadores , Colina/administração & dosagem , Suplementos Nutricionais , Modelos Animais de Doenças , Microbioma Gastrointestinal , Masculino , Metagenômica/métodos , Camundongos , Probióticos , Células Piramidais/metabolismoRESUMO
Whether neuronal inositol-requiring enzyme 1 (Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)-specific deficiency of Ire1α accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as "beiging" of white adipose tissue. We also demonstrate that loss of Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of Ire1α in Pomc neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed Pomc neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that Ire1α-Xbp1s and associated molecular targets link ER stress in arcuate Pomc neurons to aspects of normal energy and glucose homeostasis.
Assuntos
Glicemia/metabolismo , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/genética , Metabolismo Energético/genética , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/genética , Termogênese/genética , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/citologia , Núcleo Arqueado do Hipotálamo/metabolismo , Western Blotting , Temperatura Baixa , Glucose/metabolismo , Teste de Tolerância a Glucose , Homeostase/genética , Hipotálamo/metabolismo , Imuno-Histoquímica , Resistência à Insulina/genética , Leptina/metabolismo , Masculino , Camundongos , Técnicas de Patch-Clamp , Pró-Opiomelanocortina/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Emodin is an effective active ingredient extracted from Chinese herbal medicine, which has the function of antimicrobial, anti-inflammatory, antioxidant and scavenging oxygen free radicals, inhibiting platelet aggregation, improving microcirculation, protecting various organs and tissues as well as a wide range of anti-tumor effect. Primary biliary gallbladder is a common malignant tumor resection rate and lack of effective adjuvant treatment. It has been confirmed that emodin has broad spectrum antitumor effect, whereas, whether it has curative effect in the treatment of gallbladder carcinoma there is no reliable clinical trials confirmed that its resistance to gallbladder carcinoma function needs further experimental research. In this review, we report the research progress of emodin anti-gallbladder carcinoma.