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

Autor(es)

Mace, Ruan Carlos de ; Lima, Gabriely Cristina Alves ; Cardinali, Camila Aparecida Erreiras Fernandes ; Gonsalves, Alisson Carvalho ; Portari, Guilherme Vannucchi ; Guerra-Shinohara, Elvira Maria ; Leboucher, Antoine ; Junior, Jose Donato ; Kleinridders, Andrea ; Torrao, Andrea da Silva

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 306, p. 13-pg., 2022-08-05.

Resumo

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. (AU)

• Processo FAPESP: 17/10801-1 - Benfotiamina e hormônio tireoideano: influência sobre o metabolismo energético neuronal e a progressão da neurodegeneração em um modelo experimental semelhante à Doença de Alzheimer
• Beneficiário: Andréa da Silva Torrão
• Modalidade de apoio: Auxílio à Pesquisa - Regular