Neurotoxicology
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The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes among occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or prenatal exposure.
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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element, a cis-acting regulatory element that increases expression of detoxifying enzymes and antioxidant proteins. Kelch-like ECH associating protein 1 (Keap1) protein is a negative regulator of Nrf2. Previous work has shown that genetic overexpression of Nrf2 is protective in vitro and in vivo. ⋯ Moreover, Keap1 siRNA resulted in a persistent upregulation of the Nrf2-ARE pathway and protection against oxidative stress in primary astrocytes. Keap1 siRNA injected into the striatum was also modestly protective against MPTP-induced dopaminergic terminal damage. These data indicate that activation of endogenous intracellular levels of Nrf2 is sufficient to protect in models of oxidative stress and Parkinson's disease.
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Biological and psychosocial factors affect child development and behavior. Whereas biological underpinnings behind the neurotoxic effects of lead are studied extensively, the effects of psychosocial factors contributing to poor behavioral outcomes in lead-exposed children are not well understood. Parental attributes and practices may moderate or mediate the effects of lead on children's behavioral outcomes. ⋯ BLLs ≥ 5 μg/dL in mother or child were associated with lower maternal perceptions of being skilled at discipline (p<0.05). Maternal anemia was associated with lower likelihood that mothers would let their children explore and play (p<0.05), whereas child anemia was associated with maternal perception of lower emotional support (p<0.01). In addition to shared environmental exposures, parenting and family interactions need to be considered as potentially contributing factors to poorer outcomes in lead-exposed children.
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Methylmercury (MeHg) is a widespread environmental toxicant with major actions on the central nervous system. Among the neurons reportedly affected in cases of Hg poisoning are motor neurons; however, the direct cellular effects of MeHg on motor neurons have not been reported. Ratiometric fluorescence imaging, using the Ca(2+)-sensitive fluorophore fura-2, was used to examine the effect of MeHg on Ca(2+) homeostasis in primary cultures of mouse spinal motor neurons. ⋯ The voltage-dependent Na(+) channel blocker tetrodotoxin (TTX, 1 μM) did not alter the MeHg-induced increases in fura-2 fluorescence ratio. Thus, MeHg alters Ca(2+) homeostasis in mouse spinal motor neurons through excitatory amino acid receptor-mediated pathways, and nifedipine and ω-conotoxin-GVIA-sensitive pathways. Spinal motor neurons are highly sensitive to this effect of acute exposure to MeHg.