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Low levels of total cholesterol reported in the serum of FXS patients, and evidence that FMRP targets a subset of mRNAs encoding proteins of lipid synthesis and transport suggests that the cholesterol metabolism impairments could be involved in FXS. Thus, the aim of the presented work was to investigate the modulations of the cholesterol biosynthetic pathway and its end-products in a recently developed Fmr1-\u0394exon 8 rat model of FXS. Here, we show that this experimental model mimics what is found in FXS patients, exhibiting a lower serum cholesterol content, accompanied by a reduction in food intake and body weight compared to WT animals. Moreover, alterations of proteins committed to cholesterol synthesis and uptake have been observed in the amygdala, prefrontal cortex and nucleus accumbens. Interestingly, the end-products show a brain region-dependent modulation in Fmr1-\u0394exon 8 rats. Overall, our results demonstrate that the cholesterol biosynthetic pathway is altered in some brain regions of this preclinical model of FXS. This finding has relevance for future studies to delve deeper into the involvement of this metabolic process in FXS, and thus its possible role as a therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms23063408","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T13:24:59Z","timestamp":1647869099000},"page":"3408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9135-567X","authenticated-orcid":false,"given":"Martina","family":"Parente","sequence":"first","affiliation":[{"name":"Department of Science, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9979-1142","authenticated-orcid":false,"given":"Claudia","family":"Tonini","sequence":"additional","affiliation":[{"name":"Department of Science, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Buzzelli","sequence":"additional","affiliation":[{"name":"Department of Science, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Science, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-6045","authenticated-orcid":false,"given":"Viviana","family":"Trezza","sequence":"additional","affiliation":[{"name":"Department of Science, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2511-6168","authenticated-orcid":false,"given":"Valentina","family":"Pallottini","sequence":"additional","affiliation":[{"name":"Department of Science, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy"},{"name":"Neuroendocrinology Metabolism and Neuropharmacology Unit, IRCSS Fondazione Santa Lucia, Via del Fosso Fiorano 64, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Musetti, A., Manari, T., Dioni, B., Raffin, C., Bravo, G., Mariani, R., Esposito, G., Dimitriou, D., Plazzi, G., and Franceschini, C. 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