Percorrer por autor "Araujo, Renata Sandres de Souza"
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- Controlling the effect of injection in the hypothalamus of diet induced obese micePublication . Araujo, Renata Sandres de Souza; Nóbrega, ClévioDiet-induced obesity causes a central inflammatory process in the brain, more specifically in the arcuate nucleus of the hypothalamus; in addition to substantially altering cholesterol homeostasis in the brain. The brain is one of the richest organs in cholesterol and cholesterol homeostasis has proved to be very important not only to maintain healthy brain physiology, but also directly influencing the whole-body homeostasis. In addition, several metabolic disorders are correlated with different neurodegenerative diseases. Cholesterol in the brain is converted primarily to 24-hydroxycholesterol (24-OHC) by CYP46A1. Changes in oxysterol metabolism have been correlated with obesity. Previous studies from our laboratory have identified CYP46A1 as a relevant therapeutic target, not only for Machado de Joseph disease, but also for other neurodegenerative diseases. One of these studies revealed that the silencing of the expression of the Cyp46a1 gene (using AAV5-shCyp46A1), in the hypothalamus of C57BL/6J mice fed a low fat diet (Chow) (control diet) and a high fat diet (HFD), had a profound impact on the dysregulation of the entire physiological process of body homeostasis. In this sense, additional studies became necessary to demonstrate that the effect of silencing the Cyp46a1 gene in the arcuate nucleus was specific, discarding the effect of the surgical procedure or viral vectors administration. Thus, in this study, our main objective was to control the effect of Cyp46a1 silencing on the hypothalamus (arcuate nucleus). For this, through stereotaxic surgery, a control gene (GFP) was delivered by AAV vectors in the arcuate nucleus; both in animals fed with Chow ration and those fed with HFD ration. The project's main hypothesis is that the GFP protein does not interfere in the physiology of the hypothalamus and consequently in the metabolism of the whole-body, regardless of diet. Our data confirm that stereotaxic surgery and GFP expression did not alter the homeostasis of the hypothalamus and, consequently, there was no change in the whole-body metabolism of the mice.