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Insights on the modulatory role of non-digestible saccharides against developmental neurotoxicants

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Relation http://ir.cftri.com/12166/
 
Title Insights on the modulatory role of
non-digestible saccharides against
developmental neurotoxicants
 
Creator Gokul, K.
 
Subject 05 Carbohydrate Biochemistry
17 Toxicology
 
Description Non-digestible oligosaccharides (NDOs) positively influence health
targeting the indigenous gut bacterial community. Specifically, during
pregnancy, NDOs may be used to abrogate various pregnancy-related
metabolic disturbances. Strong evidence implicates that numerous chemicals
can cause neurodevelopmental toxicity, and the developing brain is uniquely
vulnerable to such exposures during in utero/ postnatal period. Further, there is
now compelling evidence for a link between the enteric microbiota and brain
function. Thus from the neurodevelopmental perspective, the microbiota has
emerged as a key modulator in neurodevelopment. Accordingly, this proposal
aims to assess the potential of selected NDOs during pregnancy to alleviate
developmental neurotoxicity in rodent model. The second objective was to
investigate the utilization of Drosophila model to assess the efficacy of NDOs
and NDO-enriched phytochemical extract to alleviate neurotoxic implications.
In the prenatal model, initially recapitulating the impact of acrylamide
(ACR, 200 ppm in drinking water) exposure during gestation days (GD 6–19),
inulin (IN) and combined fructo- and xylo-oligosaccharides (FOS + XOS)
supplements to pregnant rats significantly attenuated ACR-induced changes in
exploratory activity and gestational outcomes. More importantly, prebiotic
supplements augmented cecal bacterial numbers that correlated well with the
neurorestorative effect as evidenced by restored dopamine, γ-aminobutyric
acid levels, and acetylcholinesterase. Cytoarchitectural damage evidenced with
gliosis, pyknotic nuclei together with decreased Purkinje cells were prevented
with FOS + XOS supplements. Further, the neuroprotective effects of IN in the
maternal striatum and other limbic structures/ fetal milieu was tested employing
rotenone (ROT, a dopaminergic neurotoxin) neurotoxicity model. The
propensity of IN and FOS + XOS supplements to attenuate the impact of
perinatal ACR exposure (GD6–LD21) in dams and postnatal day (PND 21)
offsprings was investigated in terms of its effects on neuropathic signs, litter
outcomes, preweaning behavioral alterations, offspring developmental
landmarks, brain mitochondrial oxidative dysfunctions and neurotoxicity.
Further, in the Drosophila model NDOs enrichment markedly abrogated the
Abstract
xiii
ACR and ROT induced lethality, locomotor deficits, and oxidative stress. The
protective effect was also discernible in the cholinesterase and motor neuronal
markers among flies co-exposed to ROT (500 μM) and NDO-enriched
phytochemical (tomato seed aqueous extract) supplements.
Taken together, current findings clearly demonstrate the protective ability
of NDOs to render resistance following neurotoxicant exposure and during the
neurodevelopmentally sensitive period in the rat model. In this regard, it is
proposed the use of microbial-based therapeutics to modulate beneficial
microbiota, which possesses the propensity to abrogate the neurotoxic
implications during brain development. Evidence obtained in the Drosophila
system demonstrates the utility value of the model in understanding the
propensity of NDOs to modulate experimentally induced oxidative stress and
neurotoxicity.
 
Contributor Dr., Muralidhara
 
Date 2015
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Language en
 
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Identifier http://ir.cftri.com/12166/1/Gokul%20PhD%20Thesis.pdf
Gokul, K. (2015) Insights on the modulatory role of non-digestible saccharides against developmental neurotoxicants. PhD thesis, University of Mysore.