Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate.
09 May 1969-Science (American Association for the Advancement of Science)-Vol. 164, Iss: 3880, pp 719-721
TL;DR: It is postulated that the aduls syndrome represents a multifacted nueroendocrine disturbance arising from the disruption of developing nueral centers concered in the mediation of endocrine function.
Abstract: In newborn mice subcutaneous injectionis of monosodium glutamate induced acute neuronal necrosis in several regions of developing brain including the hypothanamus. As adults, treated animals showed stunted skeletal development, marked obesity, and female sterility. Pathological changes were also found in several organs associated with endocrine function. Studies of food consumption failed to demonstrate hyperphagia to explain the obesity. It is postulated that the aduls syndrome represents a multifacted nueroendocrine disturbance arising from the disruption of developing nueral centers concered in the mediation of endocrine function.
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TL;DR: A role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity is indicated.
Abstract: Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.
7,347 citations
01 Jan 1986
TL;DR: It is suggested that glutamate plays a key role in ischemic brain damage, and that drugs which decrease the accumulation of glutamate or block its postsynaptic effects may be a rational therapy for stroke.
Abstract: Information obtained over the past 25 years indicates that the amino acid glutamate functions as a fast excitatory transmitter in the mammalian brain. Studies completed during the last 15 years have also demonstrated that glutamate is a powerful neurotoxin, capable of killing neurons in the central nervous system when its extracellular concentration is sufficiently high. Recent experiments in a variety of preparations have shown that either blockade of synaptic transmission or the specific antagonism of postsynaptic glutamate receptors greatly diminishes the sensitivity of central neurons to hypoxia and ischemia. These experiments suggest that glutamate plays a key role in ischemic brain damage, and that drugs which decrease the accumulation of glutamate or block its postsynaptic effects may be a rational therapy for stroke.
2,331 citations
TL;DR: On average, NMDA receptors activation may be able to trigger lethal injury more rapidly than AMPA or kainate receptor activation, perhaps reflecting a greater ability to induce calcium influx and subsequent cellular calcium overload.
Abstract: Excitotoxicity refers to the ability of glutamate or related excitatory amino acids to mediate the death of central neurons under certain conditions, for example, after intense exposure. Such excitotoxic neuronal death may contribute to the pathogenesis of brain or spinal cord injury associated with several human disease states. Excitotoxicity has substantial cellular specificity and, in most cases, is mediated by glutamate receptors. On average, NMDA receptors activation may be able to trigger lethal injury more rapidly than AMPA or kainate receptor activation, perhaps reflecting a greater ability to induce calcium influx and subsequent cellular calcium overload. It is possible that excitotoxic death may share some mechanisms with other forms of neuronal death.
2,326 citations
TL;DR: In this paper, it was shown that either blockade of synaptic transmission or specific antagonism of postsynaptic glutamate receptors greatly diminishes the sensitivity of central neurons to hypoxia and ischemia.
Abstract: Information obtained over the past 25 years indicates that the amino acid glutamate functions as a fast excitatory transmitter in the mammalian brain. Studies completed during the last 15 years have also demonstrated that glutamate is a powerful neurotoxin, capable of killing neurons in the central nervous system when its extracellular concentration is sufficiently high. Recent experiments in a variety of preparations have shown that either blockade of synaptic transmission or the specific antagonism of postsynaptic glutamate receptors greatly diminishes the sensitivity of central neurons to hypoxia and ischemia. These experiments suggest that glutamate plays a key role in ischemic brain damage, and that drugs which decrease the accumulation of glutamate or block its postsynaptic effects may be a rational therapy for stroke.
2,283 citations
TL;DR: 'The following abbreviations have been used in the text'; I3-N-uxalyl-L-a,l3diaminu-prupiunic acid; ACPD, Trans-l-aminu-cydupentyl-I,3-dicarbuxylate; AMPA, a aminU-3-hydruxy-5-methyl-isoxazole-4-propionate; AP4, 2-
Abstract: 'The following abbreviations have been used in the text; I3-L-ODAP, I3-N-uxalyl-L-a,l3diaminu-prupiunic acid; ACPD, Trans-l-aminu-cydupentyl-I,3-dicarbuxylate; AMPA, a aminu-3-hydruxy-5-methyl-isoxazole-4-propionate; AP4, 2-amino-4-phosphonobutyrate; AP5, 2-amino-5-phuphonovalerate; ASP, aspartate; CNQX, 6-cyano-7-nitro-quinoxaline-2,3-dione; CPP, 3-(2-earboxypiperazin-4-yl)prupyl-l -phosphate; cyelo-Leu, eydo-Ieucine; DAA, D-a amino-adipate; DGG, y-D-glutamylglycine; DNQX, 6,7-dinitro-quinoxaline-2,3dione; EAA, excitatory amino acids; GABA, gamma-aminu-butyric acid; GDEE, glutamate diethyl ester; GLU, glutamate; GL Y, glycine; HA-966, 3-amino-l-hydroxypyrrolidone-2; lBO, ibotenate; IP, inositol phosphate; KA, kainate; KYN, kynurenate; MK-801, dibenzoeyclohepteneimine; NMDA, N-methyl-D-aspartate; PCP, phencyclidine; QA, quisqualate; SER, serine; SOP, serine O-phosphate; TCP, 1-[1-(2-thienyl)-eyclohexyIJpiperidine
2,226 citations
References
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TL;DR: During an investigation of the influence of various substances of biochemical importance upon the progress in the mouse of an hereditary retinal dystrophy it was observed that the parenteral administration of sodium L-glutamate damaged the inner layers of the retina, which are not themselves involved in the genetic lesion.
Abstract: L-Glutamic acid and its sodium salt have been widely used in the oral treatment of petit mal and mental deficiency (e. g., Zimmerman, Burgemeister, and Putnam, 1949; Milliken and Standen, 1951). Single doses of 20-30 gm. have also been administered intravenously without permanent illeffects (Sapirstein, 1943; Elman, 1946; Mayer-Gross and Walker, 1949; Weil-Malherbe, 1949). During an investigation of the influence of various substances of biochemical importance upon the progress in the mouse of an hereditary retinal dystrophy it was observed that the parenteral administration of sodium L-glutamate damaged the inner layers of the retina, which are not themselves involved in the genetic lesion. Since this lesion could also be produced in normal mice, a limited study was made of its histological development and the conditions necessary for its appearance in mouselings and adults of the Strong A2 (Glaxo) strain. Among substances related chemically or physiologically to glutamate, which were also
1,077 citations
312 citations
TL;DR: Monosodium L-glutamate is the cause of the Chinese restaurant syndrome and can precipitate headaches, and in appropriate doses it causes burning sensations, facial pressure, and chest pain.
Abstract: Monosodium L-glutamate is the cause of the Chinese restaurant syndrome and can precipitate headaches. In appropriate doses it causes burning sensations, facial pressure, and chest pain. These are pharmacological effects obeying a dose-effect relationship. There is considerable variation in oral threshold does among individuals.
262 citations
TL;DR: Preliminary examinations of animals one year after glutamate treatment showed receptor deterioration in albino animals and further retinal deterioration in both groups, and a description is given of normal synaptic arrangements.
Abstract: Sodium-L-glutamate was administered to post-natal Swiss albino and agouti C3H/HeJ “rodless” mice. In both cases there was at two months a marked reduction in myelinated axons of the optic nerve from about 25,000 to less than 225 axons but Swiss mice had more ganglion cell somas than axons. Glutamate-treated eyes seemed smaller and the lenses were 65% of the weight of control lenses. The inner nuclear layer of Swiss-glutamate retinas was reduced from 5–7 nuclei deep to 1–2. In treated Swiss mice the receptor concentration appears unchanged and electron microscopy revealed that both spheroidal and pedicular receptor terminals were contacted by presumed neurites of second order neurons. There was a small, relative increase in terminals of bipolar neurons in the markedly reduced inner plexiform layer. Relative to these findings a description is given of normal synaptic arrangements. In glutamate-treated “rodless” mice at two months the retina contained two rows of nuclei. Imbricated processes of glial cells of Muller faced the pigment epithelium and the retina contained scattered ganglion cells, bipolar cells, and other neurons less readily characterized. At two months most glutamate-treated mice, rod containing or “rodless,” had a direct pupillary response and a detectable but obviously weaker consensual response. Preliminary examinations of animals one year after glutamate treatment showed receptor deterioration in albino animals and further retinal deterioration in both groups. The two surviving C3H-glutamate animals possessed milky cataractous lenses, however full but sluggish direct iris constrictions could be elicited.
97 citations
TL;DR: Marked weight gains were produced in stock albino mice by single injections of goldthioglucose, and analysis of total body lipids, protein, water, and ash showed these weight gains to be primarily due to an increase in adipose tissue.
Abstract: SummaryMarked weight gains were produced in stock albino mice by single injections of goldthioglucose. Analysis of total body lipids, protein, water, and ash showed these weight gains to be primarily due to an increase in adipose tissue. This obesity occurred in approximately one-third of the survivors of sublethal doses of goldthioglucose. Except for centrolubular fatty infiltration of the liver in obese animals, no-anatomic lesions were found in the organs examined.
93 citations