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- Title
P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse.
- Authors
Pascucci, Tiziana; Colamartino, Marco; Fiori, Elena; Sacco, Roberto; Coviello, Annalisa; Ventura, Rossella; Puglisi-Allegra, Stefano; Turriziani, Laura; Persico, Antonio M.
- Abstract
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction/communication, stereotypic behaviors, restricted interests, and abnormal sensory-processing. Several studies have reported significantly elevated urinary and foecal levels of p-cresol in ASD children, an aromatic compound either of environmental origin or produced by specific gut bacterial strains. Methods: Since p-cresol is a known uremic toxin, able to negatively affect multiple brain functions, the present study was undertaken to assess the effects of a single acute injection of low- or high-dose (1 or 10 mg/kg i.v. respectively) of p-cresol in behavioral and neurochemical phenotypes of BTBR mice, a reliable animal model of human ASD. Results: P-cresol significantly increased anxiety-like behaviors and hyperactivity in the open field, in addition to producing stereotypic behaviors and loss of social preference in BTBR mice. Tissue levels of monoaminergic neurotransmitters and their metabolites unveiled significantly activated dopamine turnover in amygdala as well as in dorsal and ventral striatum after p-cresol administration; no effect was recorded in medial-prefrontal cortex and hippocampus. Conclusion: Our study supports a gene x environment interaction model, whereby p-cresol, acting upon a susceptible genetic background, can acutely induce autism-like behaviors and produce abnormal dopamine metabolism in the reward circuitry.
- Subjects
BRAIN metabolism; AUTISM spectrum disorders; HYPERACTIVITY; DOPAMINE analysis; MICE; AROMATIC compounds
- Publication
Brain Sciences (2076-3425), 2020, Vol 10, Issue 4, p233
- ISSN
2076-3425
- Publication type
Article
- DOI
10.3390/brainsci10040233