期刊
NEUROSCIENCE
卷 372, 期 -, 页码 27-37出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2017.12.053
关键词
autism; cholesterol; 3-hydroxy 3-methylglutaryl Coenzyme A reductase; isoprenoid; rats; valproic acid
资金
- PRIN, MIUR - Italy [2015SHM58M_004]
- CAL Roma Tre University - Italy
- Netherlands Organization for Scientific Research (NWO) Veni [91611052]
- Marie Curie Career Reintegration [PCIG09-GA-2011-293589]
- FIRB Futuro in Ricerca - Italy [RBFR10XKHS_001]
- SAPIENZA University - Italy [C26A15X58E]
Autism spectrum disorders (ASDs) present a wide range of symptoms characterized by altered sociability, compromised communication and stereotypic/repetitive behaviors. These symptoms are caused by developmental changes, but the mechanisms remain largely unknown. Some lines of evidence suggest an impairment of the cholesterol/isoprenoid metabolism in the brain as a possible cause, but systematic analyses in rodent models of ASDs are lacking. Prenatal exposure to the antiepileptic drug valproate (VPA) is a risk factor for ASDs in humans and generates a well-established model for the disease in rodents. Here, we studied cholesterol/isoprenoid metabolism in different brain areas of infant, adolescent and adult rats prenatally exposed to VPA. VPA-treated rats present autistic-like symptoms, they show changes in cholesterol/isoprenoid homeostasis in some brain areas, a decreased number of oligodendrocytes and impaired myelination in the hippocampus. Together, our data suggest a relation between brain cholesterol/isoprenoid homeostasis and ASDs. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
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