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Synaptogenesis is a critical process in nervous system development whereby neurons establish specialized contact sites which facilitate neurotransmission. Early life exposure to chemicals can result in persistent deficits in nervous system function at later life stages. These effects are often the result of abnormal development of synapses. Given the large(More)
This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19-21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by(More)
There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants.(More)
The generation of reactive oxygen species (ROS) and resultant oxidative stress have been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases or exposure to environmental chemicals. We have investigated intrinsic age-related differences in the ability of the various brain regions to generate ROS in the absence and(More)
The effect of hippocampal dynorphin administration on learning and memory was examined in spatial and nonspatial tasks. Bilateral infusion of dynorphin A(1-8) (DYN; 10 or 20 micrograms in one microliters) into the dorsal hippocampus resulted in a dose-related impairment of spatial working memory in a radial maze win-stay task. Subsequent experiments found(More)
Throughout development neurons undergo a number of morphological changes including neurite outgrowth from the cell body. Exposure to neurotoxic chemicals that interfere with this process may result in permanent deficits in nervous system function. Traditionally, rodent primary neural cultures and immortalized human and non-human clonal cell lines have been(More)
Neurotrophin signaling through Trk receptors is important for differentiation and survival in the developing nervous system. The present study examined the effects of CH(3)Hg on (125)I-nerve growth factor (NGF) binding to the TrkA receptor, NGF-induced activation of the TrkA receptor, and neurite outgrowth in an in vitro model of differentiation using PC12(More)
Mammals have a marked period of rapid brain growth and development (BGS), which is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching its peak around postnatal day 10. CaMKII, GAP-43 and BDNF play important roles during the BGS in mammals. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), are present and(More)
Male, Fischer-344 rats received bilateral injections of 2.5 micrograms of colchicine per site in the dorsal and ventral hippocampus. Intradentate colchicine preferentially destroyed dentate granule cells. Subsequent behavioral studies showed that 3 weeks after dosing, colchicine impaired the acquisition of a spatial, reference memory task in the Morris(More)
Using PC12 cells as a model of neuronal differentiation, we have shown that acute exposure to methylmercury (CH3Hg) inhibits nerve growth factor (NGF)-induced activation of TrkA. In the present study, we examined the effects of CH3Hg on pathways activated by NGF. NGF-induced phosphorylation of ERK1/2 in PC12 cells was time-dependent. Concurrent exposure to(More)