Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of the NMDA receptors (NMDARs) to synaptic plasticity declines during aging, and the decline is thought to contribute to memory deficits. Here, we demonstrate that an age-related shift in intracellular redox state contributes to the decline in NMDAR responses through Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). The oxidizing agent xanthine/xanthine oxidase (X/XO) decreased the NMDAR-mediated synaptic responses at hippocampal CA3-CA1 synapses in slices from young (3-8 months) but not aged (20-25 months) rats. Conversely, the reducing agent dithiothreitol (DTT) selectively enhanced NMDAR response to a greater extent in aged hippocampal slices. The enhancement of NMDAR responses facilitated induction of long-term potentiation in aged but not young animals. The DTT-mediated growth in the NMDAR response was not observed for the AMPA receptor-mediated synaptic responses. A similar increase was observed by intracellular application of the membrane-impermeable reducing agent, L-glutathione (L-GSH), through the intracellular recording pipette, indicating that the increased NMDAR response was dependent on intracellular redox state. DTT enhancement of the NMDAR response was dependent on CaMKII activity and was blocked by the CaMKII inhibitor--myristoylated autocamtide-2-related inhibitory peptide (myr-AIP)--but not by inhibition of the activity of protein phosphatases--PP1 and calcineurin (CaN/PP2B) or protein kinase C. CaMKII activity assays established that DTT increased CaMKII activity in CA1 cytosolic extracts in aged but not in young animals. These findings indicate a link between oxidation of CaMKII during aging, a decline in NMDAR responses, and altered synaptic plasticity.
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PMID:Intracellular redox state alters NMDA receptor response during aging through Ca2+/calmodulin-dependent protein kinase II. 2013 Feb

Neural circuitry is a self-organizing arithmetic device that converts input to output and thereby remodels its computational algorithm to produce more desired output; however, experimental evidence regarding the mechanism by which information is modified and stored while propagating across polysynaptic networks is sparse. We used functional multineuron calcium imaging to monitor the spike outputs from thousands of CA1 neurons in response to the stimulation of two independent sites of the dentate gyrus in rat hippocampal networks ex vivo. Only pyramidal cells were analyzed based on post hoc immunostaining. Some CA1 pyramidal cells were observed to fire action potentials only when both sites were simultaneously stimulated (AND-like neurons), whereas other neurons fired in response to either site of stimulation but not to concurrent stimulation (XOR-like neurons). Both types of neurons were interlaced in the same network and altered their logical operation depending on the timing of paired stimulation. Repetitive paired stimulation for brief periods induced a persistent reorganization of AND and XOR operators, suggesting a flexibility in parallel distributed processing. We simulated these network functions in silico and found that synaptic modification of the CA3 recurrent excitation is pivotal to the shaping of logic plasticity. This work provides new insights into how microscopic synaptic properties are associated with the mesoscopic dynamics of complex microcircuits.
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PMID:Hippocampal polysynaptic computation. 2191

The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P<0.01) and the SOD activities were lower while the MDA levels were higher (P<0.01) in the HIBD group. No significant differences in ultrastructure, the latency of F-VEPs or SOD/MDA levels were identified between the HBO-treated HIBD group and the normal control group (P>0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.
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PMID:Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage. 2734 17