Neurochemical research
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Neurochemical research · Jan 2004
ReviewBrain amino acids during hyponatremia in vivo: clinical observations and experimental studies.
Hyponatremia is a highly morbid condition, present in a wide range of human pathologies, that exposes patients to encephalopathic complication and the risk of permanent brain damage and death. Treating hyponatremia has proved to be difficult and still awaits safe management, avoiding the morbid sequelae of demyelinizing and necrotic lesions associated with the use of hypertonic solutions. During acute and chronic hyponatremia in vivo, the brain extrudes the excessive water by decreasing its content of electrolytes and organic osmolytes. ⋯ Additionally, new data are provided concerning changes in amino acid levels in different regions of the central nervous system after chronic hyponatremia. Results favor the role of taurine, glutamine, glutamate, and aspartate as the main amino acid osmolytes involved in the brain adaptive response to hyponatremia in vivo. Deeper knowledge of the adaptive overall and cellular brain mechanisms activated during hyponatremia would lead to the design of safer therapies for the hyponatremic patient.
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Neurochemical research · Jan 2004
Electroneutral cation-chloride cotransporters in the central nervous system.
Several members of the cation-chloride cotransporter (solute carrier family 12, SLC12) gene family are expressed within the central nervous system, with one family member, the K+-Cl- cotransporter KCC2, exclusive to neurons. These transporters are best known for their roles in cell volume regulation and epithelial salt transport, but are increasingly receiving attention in neuroscience. ⋯ This relationship has important implications for neuronal development, sensory perception, neuronal excitability, and the response to neuronal injury. Finally, the association between loss of function in the K+-Cl- cotransporter KCC3, with a severe peripheral neuropathy associated with agenesis of the corpus callosum, has revealed an unexpected role for K+-Cl- cotransport in the development and/or maintenance of both the central and peripheral nervous systems.
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Neurochemical research · Dec 2003
Effects of metabotropic glutamate receptor stimulation on cerebral O2 consumption and blood flow during focal cerebral ischemia in rats.
This investigation was performed to evaluate the effects of ACPD [(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid], a metabotropic glutamate receptor agonist, on cerebral O2 consumption during focal cerebral ischemia. Male Wistar rats were placed in control (n = 7) and ACPD (n = 7) groups under isoflurane anesthesia. Twenty minutes after middle cerebral artery (MCA) occlusion, gauze sponges with 10(-5) M ACPD or normal saline were placed on the ischemic cortex (IC) for a period of 40 min and were changed every 10 min. ⋯ ACPD did not change regional cerebral blood flow of the IC, but did significantly increase the oxygen extraction (7.8 +/- 0.2 vs. 6.9 +/- 0.3 ml O2/100 ml) and oxygen consumption of the IC (4.3 +/- 1.5 vs. 2.9 +/- 0.4) compared to the control IC. Our data demonstrated that topical application of 10(-5) M ACPD to the ischemic area worsened cerebral O2 balance. These data suggest that metabotropic glutamate receptors are not maximally activated during ischemia in the temporal cortex.
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Neurochemical research · Oct 2003
The production of reactive oxygen species in intact isolated nerve terminals is independent of the mitochondrial membrane potential.
Dependence on mitochondrial membrane potential (deltapsim) of hydrogen peroxide formation of in situ mitochondria in response to inhibition of complex I or III was studied in synaptosomes. Blockage of electron flow through complex I by rotenone or that through complex III by antimycin resulted in an increase in the rate of H2O2 generation as measured with the Amplex red assay. Membrane potential of mitochondria was dissipated by either FCCP (250 nM) or DNP (50 microM) and then the rate of H2O2 production was followed. ⋯ Inhibition of the F0F1-ATPase by oligomycin, which also eliminates deltapsim in the presence of rotenone and antimycin, respectively, was also without effect on the ROS formation induced by rotenone and only slightly reduced the antimycin-induced H2O2 production. These results indicate that ROS generation of in situ mitochondria in nerve terminals in response to inhibition of complex I or complex III is independent of deltapsim. In addition, we detected a significant antimycin-induced H2O2 production when the flow of electrons through complex I was inhibited by rotenone, indicating that the respiratory chain of in situ mitochondria in synaptosomes has a substantial electron influx distal from the rotenone site, which could contribute to ROS generation when the complex III is inhibited.
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Neurochemical research · Dec 2000
Calcium sequestering ability of mitochondria modulates influx of calcium through glutamate receptor channel.
The excitotoxicity of glutamate is believed to be mediated by sustained increase in the cytosolic Ca2+ concentration. Mitochondria play a vital role in buffering the cytosolic calcium overload in stimulated neurons. Here we have studied the glutamate induced Ca2+ signals in cortical brain slices under physiological conditions and the conditions that modify the mitochondrial functions. ⋯ To validate this, influx of Mn2+ through ionotropic glutamate receptor channel was monitored by measuring the quenching of Fura-2 fluorescence. Treatment of slices with oligomycin and rotenone prior to glutamate exposure conspicuously reduced the rate of glutamate induced fluorescence quenching as compared to untreated slices. Thus our data establish that the functional status of mitochondria can modify the activity of ionotropic glutamate receptor and suggest that blockade of mitochondrial Ca2+ sequestration may desensitize the NMDA receptor operated channel.