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Open AccessArticle

P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse

Department of Psychology and Centro "Daniel Bovet", Sapienza University of Rome, I-00185 Rome, Italy
IRCCS Fondazione Santa Lucia, I-00143 Rome, Italy
European Brain Research Institute EBRI, I-00161 Rome, Italy
Service for Neurodevelopmental Disorders & Laboratory of Molecular Psychiatry and Neurogenetics, University “Campus Bio-Medico”, I-00128 Rome, Italy
IRCCS Neuromed, I-86077 Pozzilli, Italy
Interdepartmental Program “Autism 0-90”, “Gaetano Martino” University Hospital, University of Messina, I-98125 Messina, Italy
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(4), 233;
Received: 12 March 2020 / Revised: 8 April 2020 / Accepted: 9 April 2020 / Published: 13 April 2020
(This article belongs to the Special Issue Advances in Autism Research)
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. View Full-Text
Keywords: autism spectrum disorder (ASD); biomarker; p-cresol; mouse social behavior; dopamine autism spectrum disorder (ASD); biomarker; p-cresol; mouse social behavior; dopamine
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Pascucci, T.; Colamartino, M.; Fiori, E.; Sacco, R.; Coviello, A.; Ventura, R.; Puglisi-Allegra, S.; Turriziani, L.; Persico, A.M. P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse. Brain Sci. 2020, 10, 233.

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