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.

Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior?

“…Kirsten et al established a mouse model for ASD by prenatal Lipopolysaccharide exposure and reported autistic like behavior and reduced NTS (protein) plasma levels in male offspring. Postnatal treatment with the anti-diabetic drug Pioglitazone corrected social and communication deficits and abolished the reduction in the NTS levels [80,81]. We found reduced Nts mRNA levels in VPA exposed male and female mice that were corrected by SAM administration.…”

Acute rapamycin treatment reveals novel mechanisms of behavioral, physiological, and functional dysfunction in a maternal inflammation mouse model of autism and sensory over-responsivity

“…Our analysis of both young and older adult MIR offspring showed a persistent elevation in pro-inflammatory cytokines in the blood and increased brain-wide increases in microglia, suggesting a chronic inflammatory state across the life-span compared to age-matched controls. Both clinical and pre-clinical studies have previously reported some success in the clinical treatment of ASD in children with an anti-inflammatory drug, pioglitazone, which improved behavioral phenotypes along with reducing neuro-inflammation [216][217][218][219][220][221][222][223][224] . We also found a concomitant chronic elevation of mTOR signaling in the neurogenic adult subventricular niche 118 and now in several more regions in adult (cortex, amygdala, and striatum).…”