Barrier Mechanisms in the Developing Brain

Saunders, NR; Liddelow, Shane A.; Dzięgielewska, Katarzyna M.

doi:10.3389/fphar.2012.00046

Cited by 429 publications

(359 citation statements)

References 155 publications

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“…It also shows different influx of amino acids either due to a deficient blood brain barrier or to increased transport mechanisms (Saunders et al, 2012 and references herein). These factors may result in subtle changes in brain glutamate concentration related to environmental toxicant exposure, which eventually could be associated with neurological deficits observed in exposed children (Grandjean and Landrigan, 2006;Sunyer et al, 2010).…”

Section: Glutamate Transport In Human Placenta Is Inhibited By Enviromentioning

confidence: 99%

Influence of prenatal exposure to environmental pollutants on human cord blood levels of glutamate

et al. 2014

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Alteration of the glutamatergic system may be one mechanistic pathway. We aimed to determine whether mercury and seven OCs, including PCBs 138, 153, and 180, DDT and DDE, hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (β-HCH) influence the cord levels of two excitatory amino acids, glutamate and aspartate. Secondly, we evaluated if this association was mediated by glutamate uptake measured in human placental membranes. The study sample included 40 newborns from a Spanish cohort selected according to cord mercury levels. We determined the content of both amino acids in cord blood samples by means of HPLC and assessed their associations with the contaminants using linear regression analyses, and the effect of the contaminants on glutamate uptake by means of [ 3 H]-aspartate binding in human placenta samples. PCB138, β-HCH, and the sum of the 3 PCBs and seven OCs showed a significant negative association with glutamate levels (decrease of 51, 24, 56 and 54 %, respectively, in glutamate levels for each 10-fold increase in the contaminant concentration). Mercury did not show a significant correlation neither with glutamate nor aspartate levels in cord blood, however a compensatory effect between THg and both PCB138, and 4,4'-DDE was observed. The organo-metallic derivative methylmercury completely inhibited glutamate uptake in placenta while PCB138 and β-HCH partially inhibited it (IC50 values: 4.9 ± 0.8 μM, 14.2± 1.2nM and 6.9± 2.9nM, respectively).We conclude that some environmental toxicants may alter the glutamate content in the umbilical cord blood, which might underlie alterations in human development.Key words: methylmercury, polychlorobiphenyl (PCB), organochlorine pesticides, placenta, umbilical cord blood, glutamate, transport, pollutants. 3 IntroductionSocial and economic development have been mediated by strong industrial growth involving the synthesis, use and release of large numbers of chemicals many of which are potentially harmful to human health and the environment (Li and Macdonald, 2005;Porta et al., 2012).Several of these chemicals, e.g. lead, mercury, polychlorinated biphenyls (PCBs), arsenic and toluene, have been associated to subclinical brain dysfunction and neurodevelopmental disorders such as poorer cognitive and motor development, attention deficit, hyperactivity, and sensory deficits but the underlying processes leading to these effects are still unknown (Grandjean and Landrigan, 2006). Pollutants come from several different sources, move on the environment and eventually accumulate in the food chain. Daily exposure to environmental persistent pollutants results in detectable levels of metals, PCBs and organochlorine pesticides in woman bodies (Woodruff et al., 2011). During pregnancy, the pollutants accumulated by the women can reach the fetus crossing the placenta. Although the placenta regulates the exchange of nutrients and oxygen between mother and fetus and acts as a barrier of many toxicants, it does not provide protection against certain environmental contaminants (Proui...

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Section: Glutamate Transport In Human Placenta Is Inhibited By Enviromentioning

confidence: 99%

Influence of prenatal exposure to environmental pollutants on human cord blood levels of glutamate

et al. 2014

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“…This is due to placenta does not block the passage of fluoride from maternal circulation to foetal circulation 32 and poorly developed blood brain barrier (BBB). The poorly formed BBB vasculature fails to control the entry of fluoride into the brain 6 .…”

Section: Discussionmentioning

confidence: 99%

“…leaky, or even absent, rendering the developing brain more vulnerable to fluoride entering the fetal circulation from the mother 6 . Once it enter into the brain it can cause adverse effects on the brain cell ultra structure, metabolism, enzymes, the oxidantantioxidant status and on neurotransmitters and thus overall metabolism of brain 7,8 .…”

mentioning

confidence: 99%

Untitled

2018

IJPSR

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This study reports protective effect of Abelmoschus moschatus seed extract against sodium fluoride (NaF) induced alterations in behavior correlated with neurochemical changes in developing brain of rats. Excessive intake of fluoride during pregnancy cross the blood brain barrier (BBB) and cause adverse effects on neonatal development. As the BBB in fetuses, neonates and infants is immature, it cannot provide protection against the entries. The pregnant wistar rats were randomly categorized into six groups of five animals each. Group I is of control rats received normal tap water. Group II is NaF exposed group with 20 ppm (or 20 mgkg -1 body wt.) in their drinking water. Group III rats were treated with A. moschatus aqueous extract (AMAE) (300 mgkg -1 body wt./day/rat) along with NaF water (20 ppm). Group IV rats were treated with A. moschatus ethanolic extract (AMEE) (300 mgkg -1 body wt./day/rat) along with NaF water (20 ppm).Group V and VI rats were treated with AMAE (300 mgkg -1 body wt./day/rat), and AMEE (300 mgkg -1 body wt./day/rat) respectively. On 1 st , 7 th , 14 th , 21 st and 30 th day (postpartum days), the pups were sacrificed to assess oxidative stress markers (LPO, CAT), and measured body weight, brain weight, BSI, and estimated protein content of brain tissue of all experimental groups. On post-natal day 21 and day 30 pups behavioral activity (rota rod, hot plate test) was measured. Fluoride exposure significantly increased lipid peroxidation and decreased the activity of catalase, and decreased body and brain weight, BSI and also protein content of the brain of pups indicating oxidative stress and inhibited antioxidant system and protein synthesis which were reverted on administration of AMAE and AMEE against NaF intoxication. The altered behavioral responses on NaF exposure were also reversed to that of control. Hence, this study proves the vulnerability of developing brain to fluoride toxicity during development and growth and protection offered by AMAE and AMEE towards neurotoxicity of NaF.

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“…Indeed, in recent studies using pregnant mice, Gd was deposited in the brain of dams and pups with higher concentration in the pup brain after GBCA injection [8,9]. Higher levels of Gd deposition in the fetal brain may be due to the immaturity of the blood-brain barrier [10] and the bloodcerebrospinal fluid barrier, both of which are not fully developed in the perinatal period [6,11].…”

mentioning

confidence: 99%