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Subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in schizophrenia and dissociative states, including impaired performance of frontal lobe-sensitive tests. Several lines of evidence suggest that ketamine may impair PFC(More)
Carbon monoxide, an activator of guanylyl cyclase, is formed by the action of the enzyme heme oxygenase. By in situ hybridization in brain slices, discrete neuronal localization of messenger RNA for the constitutive form of heme oxygenase throughout the brain has been demonstrated. This localization is essentially the same as that for soluble guanylyl(More)
The present study was performed to assess the role of excitatory amino acid and dopamine receptors on associative functions of the prefrontal cortex (PFC) of the rat. Spatial delayed alternation was used as a PFC-sensitive cognitive task. In addition, in vivo microdialysis was used to assess the release of dopamine in the PFC. The noncompetitive NMDA(More)
The occurrence of stress and anxiety disorders has been closely associated with alterations of the amygdala GABAergic system. In these disorders, dysregulation of the serotonergic system, a very important modulator of the amygdala GABAergic system, is also well recognized. The present study, utilizing a learned helplessness stress rat model, was designed to(More)
Cancer cells display high rates of aerobic glycolysis, a phenomenon known historically as the Warburg effect. Lactate and pyruvate, the end products of glycolysis, are highly produced by cancer cells even in the presence of oxygen. Hypoxia-induced gene expression in cancer cells has been linked to malignant transformation. Here we provide evidence that(More)
BACKGROUND Erythropoietin (Epo), induced by hypoxia, controls the survival, proliferation, and differentiation of Epo receptor (EpoR)-bearing erythroid progenitors and plays a role in the protection of neurons from hypoxic damage. Hypoxia in malignant disease is associated with invasion, metastasis, resistance to therapy, and selection for cells with(More)
Erythropoietin (EPO) stimulates the growth of erythroblasts in the bone marrow (C. Lacombe and P. Mayeux, NEPHROL: DIAL: TRANSPLANT:, 14 (SUPPL: 2): 22-28, 1999). We report basal and hypoxia-stimulated expression of EPO and its receptor, EPOR, in human breast cancer cells, and we demonstrate EPO-stimulated tyrosine phosphorylation and the proliferation of(More)
Tissue hypoxia is a characteristic property of cervical cancers that makes tumors resistant to chemo- and radiation therapy. Erythropoietin (Epo) is a hypoxia-inducible stimulator of erythropoiesis. Acting via its receptor (EpoR), Epo up-regulates bcl-2 and inhibits apoptosis of erythroid cells and rescues neurons from hypoxic damage. In addition to human(More)
Continuous hydroxylation of the HIF-1 transcription factor alpha subunit by oxygen and 2-oxoglutarate-dependent dioxygenases promotes decay of this protein and thus prevents the transcriptional activation of many genes involved in energy metabolism, angiogenesis, cell survival, and matrix modification. Hypoxia blocks HIF-1alpha hydroxylation and thus(More)
High lactate generation and low glucose oxidation, despite normal oxygen conditions, are commonly seen in cancer cells and tumors. Historically known as the Warburg effect, this altered metabolic phenotype has long been correlated with malignant progression and poor clinical outcome. However, the mechanistic relationship between altered glucose metabolism(More)