Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

Environmental insults including pesticide exposure and their entry into the immature brain are of increased
concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota
influences in utero fetal development via modulation of host’s microbial composition with prebiotics. Hence we
examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate
brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT)
neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6–19 with 0
(control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general
fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and
cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with
inulin (2×/day, 2 g/kg/bw) on GD 0–21 were administered ROT (50 mg/kg, GD 6–19). IN supplements increased
maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related
behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD
19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation
biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and
fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROTinduced
reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential
role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative
disorders