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Zinc is present in presynaptic nerve terminals throughout the mammalian central nervous system and likely serves as an endogenous signaling substance. However, excessive exposure to extracellular zinc can damage central neurons. After transient forebrain ischemia in rats, chelatable zinc accumulated specifically in degenerating neurons in the hippocampal(More)
Zn(2+) is the second most prevalent trace element in the body and is present in particularly large concentrations in the mammalian brain. Although Zn(2+) is a cofactor for many enzymes in all tissues, a unique feature of brain Zn(2+) is its vesicular localization in presynaptic terminals, where its release is dependent on neural activity. Although the(More)
The effects of neurotrophins on several forms of neuronal degeneration in murine cortical cell cultures were examined. Consistent with other studies, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 all attenuated the apoptotic death induced by serum deprivation or exposure to the calcium channel antagonist nimodipine. Unexpectedly,(More)
We used the ratioable fluorescent dye mag-fura-5 to measure intracellular free Zn2+ ([Zn2+]i) in cultured neocortical neurons exposed to neurotoxic concentrations of Zn2+ in concert with depolarization or glutamate receptor activation and identified four routes of Zn2+ entry. Neurons exposed to extracellular Zn2+ plus high K+ responded with a peak cell body(More)
The antagonist pharmacology of glutamate neurotoxicity was quantitatively examined in murine cortical cell cultures. Addition of 1-3 mM DL-2-amino-5-phosphonovalerate (APV), or its active isomer D-APV, acutely to the exposure solution selectively blocked the neuroexcitation and neuronal cell selectively blocked the neuroexcitation and neuronal cell loss(More)
Staurosporine, a nonselective protein kinase inhibitor, has been shown to induce apoptosis in several different nonneuronal cell types. We tested the hypothesis that staurosporine would also induce apoptosis in central neurons. Exposure of murine cortical cell cultures to 30-100 nM staurosporine induced concentration-dependent selective neuronal(More)
Quantitative concentration-toxicity relationships were determined for the injury of cultured murine cortical neurons by several excitatory amino acid (EAA) agonists. All tested agonists produced concentration-dependent neuronal injury at concentrations between 1 and 1000 microM. With 5 min exposure, glutamate, aspartate, N-methyl-D-aspartate (NMDA),(More)
This study examined the possibility that the excitotoxin-induced death of cultured cortical neurons might occur by apoptosis, specifically focusing on the slowly triggered death induced by low concentrations of excitotoxin. Cultured murine cortical neurons (days in vitro 10-12) were exposed continuously to N-methyl-D-aspartate (10-15 microM),(More)
Recent studies have implicated the ingestion of the structurally related plant excitotoxins, beta-N-methylamino-L-alanine (BMAA), and beta-N-oxalylamino-L-alanine (BOAA), in the pathogenesis of two human motor system diseases, the amyotrophic lateral sclerosis-Parkinsonism-dementia complex of Guam (Guam ALS-PD), and lathyrism, respectively. We have(More)