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.

P-cresol alters brain dopamine metabolism and exacerbates autism-like behaviors in the BTBR mouse / Pascucci, T.; Colamartino, M.; Fiori, E.; Sacco, R.; Coviello, A.; Ventura, R.; Puglisi-Allegra, S.; Turriziani, L.; Persico, A. M.. - In: BRAIN SCIENCES. - ISSN 2076-3425. - 10:4(2020), pp. 233-248. [10.3390/brainsci10040233]

P-cresol alters brain dopamine metabolism and exacerbates autism-like behaviors in the BTBR mouse

Persico A. M.
2020

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.
2020
10
4
233
248
P-cresol alters brain dopamine metabolism and exacerbates autism-like behaviors in the BTBR mouse / Pascucci, T.; Colamartino, M.; Fiori, E.; Sacco, R.; Coviello, A.; Ventura, R.; Puglisi-Allegra, S.; Turriziani, L.; Persico, A. M.. - In: BRAIN SCIENCES. - ISSN 2076-3425. - 10:4(2020), pp. 233-248. [10.3390/brainsci10040233]
Pascucci, T.; Colamartino, M.; Fiori, E.; Sacco, R.; Coviello, A.; Ventura, R.; Puglisi-Allegra, S.; Turriziani, L.; Persico, A. M.
File in questo prodotto:
File Dimensione Formato  
Pascucci_brainsci-10-00233-v2_2020.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 777.99 kB
Formato Adobe PDF
777.99 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1250973
Citazioni
  • ???jsp.display-item.citation.pmc??? 30
  • Scopus 54
  • ???jsp.display-item.citation.isi??? 43
social impact