Benfotiamine protects against hypothalamic dysfunction in a STZ-induced model of neurodegeneration in rats.

Autor: Moraes RCM; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil; Central Regulation of Metabolism, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany. Electronic address: moraes.ruan@usp.br., Lima GCA; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil., Cardinali CAEF; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil., Gonçalves AC; Federal Institute of Education, Science and Technology Goiano, Urutaí, GO, Brazil; Laboratory of Experimental Nutrition, Institute of Health Sciences, Federal University of Triângulo Mineiro, Brazil., Portari GV; Laboratory of Experimental Nutrition, Institute of Health Sciences, Federal University of Triângulo Mineiro, Brazil., Guerra-Shinohara EM; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Brazil; Faculty of Pharmaceutical Sciences, Food and Nutrition, Federal University of Mato Grosso do Sul, Brazil., Leboucher A; Central Regulation of Metabolism, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany., Donato J Júnior; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil., Kleinridders A; Central Regulation of Metabolism, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany; Institute of Nutritional Science, Department of Molecular and Experimental Nutritional Medicine, University of Potsdam, Germany., Torrão ADS; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2022 Oct 01; Vol. 306, pp. 120841. Date of Electronic Publication: 2022 Jul 27.
DOI: 10.1016/j.lfs.2022.120841
Abstrakt: The neurodegeneration of Alzheimer's disease (AD) affects not only brain structures associate with cognition early in the progression of the disease, but other areas such as the hypothalamus, a region involved in the control of metabolism and appetite. In this context, we evaluated the effects of benfotiamine (BFT), a vitamin B1 analog that is being proposed as a therapeutical approach for AD-related cognitive alterations, which were induced by intracerebroventricular injection of streptozotocin (STZ). In addition to the already described effect of STZ on cognition, we show that this drug also causes metabolic changes which are linked to changes in hypothalamic insulin signaling and orexigenic and anorexigenic circuitries, as well as a decreased cellular integrated stress response. As expected, the supplementation with 150 mg/kg of BFT for 30 days increased blood concentrations of thiamine and its phosphate esters. This led to the prevention of body weight and fat loss in STZ-ICV-treated animals. In addition, we also found an improvement in food consumption, despite hypothalamic gene expression linked to anorexia after STZ exposure. Additionally, decreased apoptosis signaling was observed in the hypothalamus. In in vitro experiments, we noticed a high ability of BFT to increase insulin sensitivity in hypothalamic neurons. Furthermore, we also observed that BFT decreases the mitochondrial unfolded stress response damage by preventing the loss of HSP60 and reversed the mitochondria dysfunction caused by STZ. Taken together, these results suggest that benfotiamine treatment is a potential therapeutic approach in the treatment of hypothalamic dysfunction and metabolic disturbances associated with sporadic AD.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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