Abstract
ABSTRACTWe 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.
Highlights
Autism spectrum disorder (ASD) is a developmental disorder that is characterized by social, communicative and cognitive deficits and has a higher prevalence in males (DSM-IV, 1994)
Postnatal pioglitazone treatment with 0.25 mg/kg/day did not affect the performance in the T-maze task, postnatal pioglitazone treatment with 1.0 mg/kg/day increased spontaneous alternation in the rats prenatally exposed to LPS (LPS+PI1.0 group versus LPS+DMSO group, P
Both doses (0.25 and 1.0 mg/kg/day) of the post-treatment with pioglitazone decreased brain-derived neurotrophic factor (BDNF) levels in the rats that were prenatally exposed to LPS to the same levels as those in the control group
Summary
Autism spectrum disorder (ASD) is a developmental disorder that is characterized by social, communicative and cognitive deficits and has a higher prevalence in males (DSM-IV, 1994). It is considered that the etiology of autism is unknown, genetic and environmental factors (such as prenatal infections and maternal dietary disturbs) have been described as autistic triggers (Herbert, 2010; Johnson et al, 2013; Theoharides et al, 2009). (GD) 9.5] induces socialization and communication deficits as well as repetitive/restricted behavior in juvenile offspring. These behavioral impairments are found just in males and not in the female offspring (Kirsten et al, 2010a, 2012; Kirsten and Bernardi, 2017). Our model of exposure of rats to LPS during gestation induces autistic-like behaviors in juvenile offspring (Kirsten et al, 2012). The mechanisms that are involved in fetal brain disturbances include the production and release of proinflammatory cytokines within the maternal environment (circulation and placenta) (Ashdown et al, 2006; Urakubo et al, 2001; Cai et al, 2000)
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