Altered Brain Cholesterol/Isoprenoid Metabolism in a Rat Model of Autism Spectrum Disorders
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These changes suggest that low intracellular cholesterol content, as a consequence of HMGCR activity suppression in RTT fibroblasts, induces the classic feedback mechanism with activation of SREBP2 and the increase of its transcriptional targets such as LDLR and HMGCR.
“These changes suggest that low intracellular cholesterol content, as a consequence of HMGCR activity suppression in RTT fibroblasts, induces the classic feedback mechanism with activation of SREBP2 and the increase of its transcriptional targets such as LDLR (LDL receptor) and HMGCR [23,55,103,104,105,106,107].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [55]
Adolescent VPA-exposed rats showed a strong increase of membrane-attached geranylgeranylated RhoA in the cerebellum, a reduced level of the farnesylated Ras in the Nucleus Accumbens and a reduction of oligodendrocytes.
“Adolescent VPA-exposed rats showed a strong increase of membrane-attached geranylgeranylated RhoA in the cerebellum, a reduced level of the farnesylated Ras in the Nucleus Accumbens and a reduction of oligodendrocytes were observed [55].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [55]
A recent study reveals age- and region-dependent alterations of proteins involved in cholesterol metabolism in the brains of a well-established rat model based on prenatal exposure to valproic acid (VPA).
“A recent study reveals age- and region-dependent alterations of proteins involved in cholesterol metabolism in the brains of a well-established rat model [54] based on prenatal exposure to valproic acid (VPA) [55].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [55]
The MVA pathway is altered in a region-, sex-, and age-dependent manner in the brain of a preclinical model of ASD, such as rats prenatally exposed to valproate.
“the MVA pathway results altered in dependence of the region, the sex and the age in the brain of a preclinical model of ASD, such as rats prenatally exposed to valproate [22,23,24].”
From Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome (2022) · cites this paper as [22]
Cholesterol metabolism is altered in numerous neurological pathologies, including ASD.
“It is widely supported that cholesterol metabolism is altered in numerous neurological pathologies, including ASD [22].”
From Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome (2022) · cites this paper as [22]
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 70 · Cited by 57
- Authors
- Cartocci, V., Catallo, M., Tempestilli, M., Segatto, M., Pfrieger, F. W., Bronzuoli, M. R., Scuderi, C., Servadio, M., Trezza, V., & Pallottini, V.
- Affiliations
- Roma Tre University (IT)
- University of Milan (IT)
- Centre National de la Recherche Scientifique (FR)
- Sapienza University of Rome (IT)
- Corresponding author
- Pallottini, Valentina
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 372
- Pages
- 27-37
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2782332921
- Cited by
- 57
- References
- 70
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 5
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Iris (Roma Tre University) (submittedVersion)
- Funders
- MIUR (2015SHM58M_004)
- Netherlands Organization for Scientific Research (91611052)
- Marie Curie Career Reintegration (PCIG09-GA-2011-293589)
- FIRB Futuro in Ricerca (RBFR10XKHS_001)
- SAPIENZA University (C26A15X58E)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- autism spectrum disorder, cholesterol metabolism, isoprenoid metabolism, valproic acid, prenatal drug exposure, oligodendrocytes, myelination, hippocampus, autism-like behavior
- MeSH terms
- Autism Spectrum Disorder, Adenylate Kinase, Animals, Brain, Cholesterol, Disease Models, Animal, Female, Liver, Male, Oligodendroglia, Pregnancy, Prenatal Exposure Delayed Effects, Terpenes, Valproic Acid, Rats, Wistar
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
