Altered Brain Cholesterol/Isoprenoid Metabolism in a Rat Model of Autism Spectrum Disorders

Veronica Cartocci, Martina Catallo, Massimo Tempestilli, Marco Segatto, Frank W. Pfrieger, Maria Rosanna Bronzuoli, Caterina Scuderi, Michela Servadio, Viviana Trezza, Valentina Pallottini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalNeuroscience
Volume372
DOIs
Publication statusPublished - Feb 21 2018

Keywords

  • 3-hydroxy 3-methylglutaryl Coenzyme A reductase
  • autism
  • cholesterol
  • isoprenoid
  • rats
  • valproic acid

ASJC Scopus subject areas

  • Neuroscience(all)

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    Cartocci, V., Catallo, M., Tempestilli, M., Segatto, M., Pfrieger, F. W., Bronzuoli, M. R., Scuderi, C., Servadio, M., Trezza, V., & Pallottini, V. (2018). Altered Brain Cholesterol/Isoprenoid Metabolism in a Rat Model of Autism Spectrum Disorders. Neuroscience, 372, 27-37. https://doi.org/10.1016/j.neuroscience.2017.12.053