Levels and Determinants of DDT and DDE Exposure in the VHEMBE Cohort.

BackgroundAlthough indoor residual spraying (IRS) is an effective tool for malaria control, its use contributes to high insecticide exposure in sprayed communities and raises concerns about possible unintended health effects.ObjectiveThe Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort study initiated in 2012 to characterize prenatal exposure to IRS insecticides and exposures' impacts on child health and development in rural South Africa.MethodsIn this report, we describe the VHEMBE cohort and dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) serum concentrations measured in VHEMBE mothers when they presented for delivery. In addition, we applied a causal inference framework to estimate the potential reduction in population-level p,p'-DDT and p,p'-DDE serum concentrations under five hypothetical interventions. A total of 751 mothers were enrolled.ResultsSerum concentrations of p,p' isomers of DDT and DDE were above the limit of detection (LOD) in ≥98% of the samples, whereas the o,p' isomers were above the LOD in at least 80% of the samples. Median (interquartile range) p,p'-DDT and p,p'-DDE serum concentrations for VHEMBE cohort participants were 55.3 (19.0-259.3) and 242.2 (91.8-878.7) ng/g-lipid, respectively. Mothers reporting to have lived in a home sprayed with DDT for malaria control had ~5-7 times higher p,p'-DDT and p,p'-DDE serum concentrations than those who never lived in a home sprayed with DDT. Of the five potential interventions tested, we found increasing access to water significantly reduced p,p'-DDT exposure and increasing the frequency of household wet mopping significantly reduced p,p'-DDT and p,p'-DDE exposure.ConclusionOur findings suggest that several intervention approaches may reduce DDT/DDE exposure in pregnant women living in IRS communities. https://doi.org/10.1289/EHP353

Kainate Receptors Coexist in a Functional Complex with KCC2 and Regulate Chloride Homeostasis in Hippocampal Neurons

Peer reviewe

Cation Chloride Cotransporters Exist with NMDA Receptors in Molecular Complexes

In the central nervous system, the polarity of GABAergic synaptic transmission is predominantly determined by cation-chloride cotransporters NKCC1 and KCC2. During development, functional expression of chloride-loading NKCC1 decreases while chloride-extruding KCC2 is steeply upregulated and underlies the GABA switch from excitatory to inhibitory. Despite the critical role of KCC2 in inhibitory neurotransmission, excitatory kainate-type glutamate receptor subunit GluK2 interacts with and regulates KCC2 function. The aim of this study was to determine if N-methyl-D-aspartate receptors (NMDARs) interact with NKCC1 and KCC2. The salient findings of my work are: (i) NKCC1 and KCC2 interact with NMDARs in neurons throughout development and into maturity (ii) loss of NMDARs alters expression of KCC2 and (iii) traumatic brain injury alters cation-chloride cotransporter expression and interactions with NMDARs. This work contributes to our knowledge of the molecular interplay between the opposing forces of neuronal excitation and inhibition.M.Sc.2018-11-17 00:00:0

Levels and Determinants of DDT and DDE Exposure in the VHEMBE Cohort.

BackgroundAlthough indoor residual spraying (IRS) is an effective tool for malaria control, its use contributes to high insecticide exposure in sprayed communities and raises concerns about possible unintended health effects.ObjectiveThe Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort study initiated in 2012 to characterize prenatal exposure to IRS insecticides and exposures' impacts on child health and development in rural South Africa.MethodsIn this report, we describe the VHEMBE cohort and dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) serum concentrations measured in VHEMBE mothers when they presented for delivery. In addition, we applied a causal inference framework to estimate the potential reduction in population-level p,p'-DDT and p,p'-DDE serum concentrations under five hypothetical interventions. A total of 751 mothers were enrolled.ResultsSerum concentrations of p,p' isomers of DDT and DDE were above the limit of detection (LOD) in ≥98% of the samples, whereas the o,p' isomers were above the LOD in at least 80% of the samples. Median (interquartile range) p,p'-DDT and p,p'-DDE serum concentrations for VHEMBE cohort participants were 55.3 (19.0-259.3) and 242.2 (91.8-878.7) ng/g-lipid, respectively. Mothers reporting to have lived in a home sprayed with DDT for malaria control had ~5-7 times higher p,p'-DDT and p,p'-DDE serum concentrations than those who never lived in a home sprayed with DDT. Of the five potential interventions tested, we found increasing access to water significantly reduced p,p'-DDT exposure and increasing the frequency of household wet mopping significantly reduced p,p'-DDT and p,p'-DDE exposure.ConclusionOur findings suggest that several intervention approaches may reduce DDT/DDE exposure in pregnant women living in IRS communities. https://doi.org/10.1289/EHP353

Neto2-null mice have impaired GABAergic inhibition and are susceptible to seizures

Neto2 is a transmembrane protein that interacts with the neuron-specific K⁺-Cl⁻ cotransporter (KCC2) in the central nervous system (CNS). Efficient KCC2 transport is essential for setting the neuronal Cl⁻ gradient, which is required for fast GABAergic inhibition. Neto2 is required to maintain the normal abundance of KCC2 in neurons, and increases KCC2 function by binding to the active oligomeric form of this cotransporter. In the present study, we characterized GABAergic inhibition and KCC2-mediated neuronal chloride homeostasis in pyramidal neurons from adult hippocampal slices. Using gramicidin perforated patch clamp recordings we found that the reversal potential for GABA (EGABA) was significantly depolarized. We also observed that surface levels of KCC2 and phosphorylation of KCC2 serine 940 (Ser940) were reduced in Neto2⁻/⁻ neurons compared to wild-type controls. To examine GABAergic inhibition we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) and found that Neto2⁻/⁻ neurons had significant reductions in both their amplitude and frequency. Based on the critical role of Neto2 in regulating GABAergic inhibition we rationalized that Neto2-null mice would be prone to seizure activity. We found that Neto2-null mice demonstrated a decrease in the latency to pentylenetetrazole (PTZ)-induced seizures and an increase in seizure severity