Questions have been raised regarding the possible neurotoxic effects of DU in humans based on follow-up studies in Gulf War veterans, where a decrease in neurocognitive
behavior in a small population was noted. Additional studies in rodents indicated that DU readily traverses the blood-brain barrier, accumulates in specific brain regions, and results in increased oxidative stress, altered electrophysiological profiles, and sensorimotor deficits. This review summarizes the toxic potential of DU with emphasis on studies on thiol metabolite levels, high-energy phosphate levels, and isoprostane levels in primary rat cortical neurons. Studies in Caenorhabditis elegans detail the role of metallothioneins, small thiol-rich proteins, in protecting against DU exposure. In addition, recent studies
also demonstrate that only one of the check details two forms, metallothionein-1, is important in the accumulation of uranium in worms.”
“The effect of endogenous dopamine on the activity of target neurons recorded with patch clamp or Ca(2+) imaging techniques in slices has been studied to date with intrastriatal stimuli. Yet, this approach is severely handicapped by the non physiological and nonspecific stimulation of local neurons and fibers within the striatum. We now report a new juvenile and adult mouse slice preparation in which a component of the nigro-striatal dopaminergic click here pathway is preserved in its entirety, from cell bodies to axon terminals. This tilted U0126 price parasagittal slice (380-400 mu m) just medial to the subthalamic nucleus contains functional nigro-striatal neurons as assessed by morphological examination of tyrosine hydroxylase positive cell bodies and axons, combined with electrochemical assays of dopamine
release in the striatum in response to stimulation of the substantia nigra pars compacta. The nigro-striatal slice constitutes a suitable in vitro preparation to determine the impact of endogenously released dopamine on target neurons of the striatum. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Transport of the glutathione conjugates (GS-E) of electrophilic compounds generated during biotransformation of drugs and environmental pollutants is central to the mechanisms of defense against oxidative/electrophilic stress. In recent years emphasis has been placed on ATP-binding cassette (ABC) transport proteins in the transport of GS-E and their involvement in the detoxification mechanisms, including drug resistance. Recent studies, however, suggested that the majority of GS-E transport in human and rodent cells is mediated by a non-ABC, multifunctional stress-response protein, RLIP76 or RalBP1 (ral-binding GTPase activating protein 1), which also functions as an effector in the Ral-Ras-Rho signaling pathway.