Enhancement of the oxygen consumption in the hippocampal slices of the guinea pig induced by glutamate and its related substances

Nishizaki, Tomoyuki; Yamauchi, Ryohei; Okada, Yasuhiro

doi:10.1016/0304-3940(88)90429-6

Cited by 5 publications

(3 citation statements)

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“…However, we are aware of only two studies that provide direct evidence for a change in energy metabolism in response to glutamatergic agents. Nishizaki et al (1988) reported an increase in the 0, consumption of hippocampal slices in response to glutamate, kainate, and NMDA. Raley-Susman et al (1992) found that kainate increased the energy metabolism of cultured hippocampal cells, as assessed by an increase in acid production.…”

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confidence: 98%

Energy requirements of glutamatergic pathways in rabbit retina

Ames

1992

J. Neurosci.

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In vitro rabbit retina was used as an example of CNS tissue in experiments designed to measure the energy requirements associated with the activation of different types of glutamate receptors. Retinas were exposed to glutamate and to four analogs: kainate, 2-amino-4-phosphonobutyric acid (APB), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 2-amino-5-phosphonovaleric acid (APV). The changes in O2 consumption and lactate production were determined using a recently developed experimental system that permitted simultaneous measurements of the rates at which O2 was removed from the medium and acid was added. The glutamatergic agents had relatively little effect on oxidative metabolism, but they caused large changes in glycolysis. Kainate increased retinal lactate production by 50%, whereas APB, CNQX, and APV reduced it by 23%, 19%, and 35%, respectively. Glutamate increased lactate production by 16% when administered after APB, but decreased it by 12% when administered after CNQX. The changes in energy metabolism coincided with changes in electrophysiological function. Since the energy metabolism of many retinal cells was presumably not much affected by the glutamatergic agents, the changes measured as a percent of total retinal glycolysis must have reflected considerably larger fractional changes in the cells most affected. From the response to inhibitors, it seems probable that even under resting conditions in darkness, activity in glutamatergic pathways is responsible for more than 50% of the glycolytically derived energy used by the cells involved. It also seems probable (particularly from the response to kainate) that under some circumstances the cells' energy metabolism and/or transport capability cannot meet the requirements imposed by glutamate-induced increases in function.(ABSTRACT TRUNCATED AT 250 WORDS)

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confidence: 98%

Energy requirements of glutamatergic pathways in rabbit retina

Ames

1992

J. Neurosci.

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“…and by NIH Grant ROl-AGO6633 (R.M.S.). Partial support was also provided by U.S. Army CRDEC and DARPA programs (to Molecular Devices, Inc. (Nishizaki et al, 1988) suffer from limitations relating to the diffusion of oxygen from the center of tissue whose edges are damaged. These technical difficulties also limit the ability to measure directly the effects of toxic concentrations of excitatory amino acids such as glutamate.…”

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confidence: 99%

“…For example, while in vivo studies have measured metabolic parameters, such as 14C-2-deoxyglucose uptake (Cremer et al, 1988) (which affords excellent cellular resolution), the time resolution necessary for responses to receptor activation is quite poor. Further, studies with brain slices measuring oxygen consumption in response to bath application of glutamate receptor agonists (Nishizaki et al, 1988) suffer from limitations relating to the diffusion of oxygen from the center of tissue whose edges are damaged. These technical difficulties also limit the ability to measure directly the effects of toxic concentrations of excitatory amino acids such as glutamate.…”

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Effects of excitotoxin exposure on metabolic rate of primary hippocampal cultures: application of silicon microphysiometry to neurobiology

et al. 1992

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Increasing evidence implicates glutamate receptor overstimulation in the neurotoxicity associated with a host of metabolic insults, including seizures and hypoxia-ischemia. To begin to understand more completely the role of energy metabolism in the mechanism of neuron death following excitatory amino acid exposure, we investigated the effects of kainic acid exposure on metabolic rate in cultured hippocampal cells using a recently developed silicon microphysiometer. The device gives a continual real-time measure of metabolism in relatively small numbers of cells, as assessed by efflux of protons generated at least in part by ATP hydrolysis and lactic acid production.In the first half of this report, we characterize the feasibility of using this device for measuring cellular metabolism in hippocampal cultures. Metabolic rate in both astrocytes and neurons was readily detectable, with a high signal-to-noise ratio. The rate was proportional to the number of cells and was sensitive to metabolic enhancement or depression. We then utilized this device to study metabolic responses to the excitotoxin kainit acid. We observed a receptor-mediated, dose-dependent increase in metabolic rate upon stimulation by kainic acid, with an EC, of -100 PM. Exposure to toxic levels of kainic acid for 10 min produced an initial elevation (for 2 hr) in metabolic rate and then a gradual decline in metabolism over the next 8 hr that preceded a measurable loss of cell viability. This study further delineates a time window for the onset of kainic acid-induced damage.The results clearly show the feasibility of using silicon microphysiometry for assessing metabolism of brain cultures and for exploring the relationship between metabolism and synaptic activation.Activation of glutamate receptors is thought to stimulate neuronal energy consumption for the operation of the cells' energy-dependent ion homeostatic mechanisms. However, the metabolic consequences of glutamate exposure under normal conditions are not well understood, largely because direct measurement of Received May 28, 1991; revised Oct. 1, 1991; accepted Oct. 7, 1991. This work was supported by an American Heart Association, Santa Barbara Chapter, postdoctoral fellowship (K.M.R.S.) and by NIH Grant ROl-AGO6633 (R.M.S.). Partial support was also provided by U.S. Army CRDEC and DARPA programs (to Molecular Devices, Inc. (Nishizaki et al., 1988) suffer from limitations relating to the diffusion of oxygen from the center of tissue whose edges are damaged. These technical difficulties also limit the ability to measure directly the effects of toxic concentrations of excitatory amino acids such as glutamate. This determination is important because it is generally thought that exposure to excitatory amino acids is damaging when energy stores are excessively taxed because of overstimulation of receptors (Choi, 1988;Novelli et al., 1988). This excitotoxicity hypothesis rests on the assumption that the mechanism of neuron damage is energetic in nature, and yet few direct assessments of the me...

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Changes in brain energy metabolism and the early detection of Alzheimer’s disease

Hoyer

1990

New Vistas in Drug Research

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Enhancement of the oxygen consumption in the hippocampal slices of the guinea pig induced by glutamate and its related substances

Cited by 5 publications

References 4 publications

Energy requirements of glutamatergic pathways in rabbit retina

Energy requirements of glutamatergic pathways in rabbit retina

Effects of excitotoxin exposure on metabolic rate of primary hippocampal cultures: application of silicon microphysiometry to neurobiology

Changes in brain energy metabolism and the early detection of Alzheimer’s disease

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