Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome
| Autor: | Martina Parente, Claudia Tonini, Valeria Buzzelli, Emilia Carbone, Viviana Trezza, Valentina Pallottini |
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| Přispěvatelé: | Parente, Martina, Tonini, Claudia, Buzzelli, Valeria, Carbone, Emilia, Trezza, Viviana, Pallottini, Valentina |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Autism Spectrum Disorder 3-Hydroxy 3-methylglutaryl Coenzyme A reductase brain cholesterol Fmr1-Δexon 8 rat Fragile X Syndrome low-density lipoprotein receptor liver plasma prenylated proteins Catalysis Inorganic Chemistry Fragile X Mental Retardation Protein Animals Physical and Theoretical Chemistry Molecular Biology Spectroscopy Organic Chemistry Brain General Medicine Computer Science Applications Biosynthetic Pathways Rats Cholesterol Fmr1-∆exon 8 rat |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 6; Pages: 3408 |
| Popis: | Fragile X Syndrome (FXS) is the most frequent form of inherited X-linked pathology, associated with an intellectual and developmental disability, and currently considered the first monogenic cause of autism spectrum disorder (ASD). 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-Δexon 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-Δexon 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. |
| Databáze: | OpenAIRE |
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