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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Pioglitazone abolishes autistic-like behaviors via the IL-6 pathway

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Author(s):
Kirsten, Thiago Berti [1, 2] ; Casarin, Renato C. [3] ; Bernardi, Maria M. [2, 3] ; Felicio, Luciano F. [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Sao Paulo - Brazil
[2] Univ Paulista, Environm & Expt Pathol, Sao Paulo - Brazil
[3] Univ Paulista, Grad Program Dent, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PLoS One; v. 13, n. 5 MAY 23 2018.
Web of Science Citations: 8
Abstract

Autism is characterized by social deficits, communication abnormalities, and repetitive behaviors. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infections by gram-negative bacteria, induces autistic-like behaviors. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism. We selected pioglitazone to block or ease the impairments induced by LPS because although this drug was designed as an anti-diabetic drug (it has an insulin effect), it also exerts anti-inflammatory effects. Juvenile offspring were treated daily with pioglitazone, and the main behaviors related to autism, namely, socialization (play behavior) and communication (50 kHz ultrasonic vocalizations), were studied. Biomarkers linked to autism and/or pioglitazone were also studied to attempt to understand the mechanisms involved, namely, IL-6, TNFalpha, MCP-1, insulin, and leptin. Prenatal LPS exposure induced social deficits and communicational abnormalities in juvenile rat offspring as well as elevated plasma IL-6 levels. Daily postnatal pioglitazone treatment blocked the impairments found in terms of the time spent on social interaction, the number of vocalizations (i.e., autistic-like behaviors) and the elevated plasma IL-6 levels. Thus, pioglitazone appears to be a relevant candidate for the treatment of autism. The present findings may contribute to a better understanding and treatment of autism and associated diseases. (AU)

FAPESP's process: 12/07007-8 - Possible prevention or treatment of impairments induced by an early prenatal exposure to lipopolysaccharide in an experimental model of autism
Grantee:Thiago Berti Kirsten
Support Opportunities: Scholarships in Brazil - Post-Doctoral