Pioglitazone abolishes cognition impairments as well as BDNF and neurotensin disturbances in a rat model of autism

Abstract

We have shown that exposure of rats to lipopolysaccharide (LPS) during gestation induces autistic-like behaviors in juvenile offspring and pioglitazone post treatment corrects social and communication deficits. The first objective of the present study was to evaluate the cognition of the rats, because this is also a behavioral sphere committed in autism. Second, biomarkers related to pioglitazone pathways and autism were studied to try to understand their mechanisms. We used our rat model of autism and pioglitazone was administered daily to these young offspring. T-maze spontaneous alternations tests, plasma levels of brain-derived neurotrophic factor (BDNF), beta-endorphin, neurotensin, oxytocin, and substance P were all studied. Exposure of rats to LPS during gestation induced cognitive deficits in the young offspring, elevated BDNF levels and decreased neurotensin levels. Daily postnatal pioglitazone treatment abolished cognition impairments as well as BDNF and neurotensin disturbances. Together with our previous studies, we suggest pioglitazone as a candidate for the treatment of autism, because it improved the responses of the three most typical autistic-like behaviors. BDNF and neurotensin also appeared to be related to the autistic-like behaviors and should be considered for therapeutic purposes.

Keywords

• Prenatal
• Maternal immune activation
• T-maze spontaneous alternations test
• LPS
• Neuropeptides