title: Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats.
abstract: Accumulating evidence suggests that the developing brain is more susceptible to a variety of chemicals. Recent studies have shown a link between the enteric microbiota and brain function. While supplementation of non-digestible oligosaccharides during pregnancy has been demonstrated to positively influence human health mediated through stimulation of beneficial microbiota, our understanding on their neuromodulatory propensity is limited. In the present study, our primary focus was to examine whether supplementation of inulin (a well known fructan) during gestation can abrogate acrylamide (ACR)-induced oxidative impairments and neurotoxicity in maternal and fetal brain of rats. Initially, in a dose-determinative study, we recapitulated the impact of ACR exposure during gestation days (GD 6-19) on gestational parameters, extent of oxidative impairments in brain (maternal/fetal), cholinergic function and neurotoxicity. Subsequently, pregnant rats orally (gavage) administered with inulin (IN, 2 g/kg/day in two equal installments) supplements during gestation days (GD 0-19) were exposed to ACR (200 ppm) in drinking water. IN supplements significantly attenuated ACR-induced changes in exploratory activity (reduced open field exploration) measured on GD 14. Further, IN restored the placental weights among ACR exposed dams. Analysis of biochemical markers revealed that IN supplements effectively offset ACR associated oxidative stress not only in the maternal brain, but in the fetal brain as well. Elevated levels of protein carbonyls in maternal brain regions were completely normalized with IN supplements. More importantly, IN supplements significantly augmented the number of Bifidobacteria in the cecum of ACR rats which correlated well with the neurorestorative effect as evidenced by restored dopamine levels in the maternal cortex and fetal brain acetylcholinesterase activity among ACR-exposed dams. Further, IN supplements also conferred significant protection against mitochondrial dysfunction induced by ACR in both milieus. Although the precise mechanism/s by which IN supplements during pregnancy attenuate ACR induced neurotoxic impact merits further investigations, we hypothesize that it may mediate through enhanced enteric microbiota and abrogation of oxidative stress. Further, our study provides an experimental approach to explore the neuroprotective role of prebiotic oligosaccharides during pregnancy in reducing the adverse impact of developmental neurotoxicants.
authors: Department of Biochemistry and Nutrition, CSIR-Central Food Technological Research Institute (CFTRI), Mysore 570020, Karnataka, India.
authors: Gokul
authors: G
authors: Krishna
authors: Department of Biochemistry and Nutrition, CSIR-Central Food Technological Research Institute (CFTRI), Mysore 570020, Karnataka, India. Electronic address: mura16@yahoo.com.
authors: Muralidhara
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D020106:Acrylamide / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002432:Cecum / Q000187:drug effects / Q000382:microbiology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D007444:Inulin / Q000008:administration & dosage*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D020106:Acrylamide; D007444:Inulin; D000110:Acetylcholinesterase; D004298:Dopamine
keywords: Acrylamide; Fetus; Gestation; Inulin; Oxidative stress; Prebiotic