Nitric oxide synthase-, N -methyl- d -aspartate receptor-, glutamate- and aspartate-immunoreactive neurons in the mouse arcuate nucleus: effects of neonatal treatment with monosodium glutamate

Xue, Yangkui; Wong, Peter T.-H.; Leong, Siew Meng

doi:10.1007/s004010050752

Cited by 14 publications

(10 citation statements)

References 35 publications

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“…The present data showed that in the arcuate nucleus from control animals both neuronal and glial cells conformed to standard descriptions 19,20,26 . By contrast, in NMA‐treated rats, LM showed a typical marked cell depletion; furthermore, degenerated cells were identified by their pyknotic nuclei and edematous swelling of the surrounding cytoplasmic compartment giving the typical appearance of a “bull's eye.” These findings are in agreement with previous studies that reported cell loss and the appearance of degenerated neurons in the arcuate nucleus of rats and mice after NMDA receptor agonist administration 18–21 . At ultrastructural level, NMA induced several alterations including chromatin margination, nuclear shrinkage, mitochondria with matrix dilution, dilated endoplasmic cisternae, and electron dense cytoplasm.…”

Section: Discussionsupporting

confidence: 93%

“…Since it can be easily administered and rapidly enters the brain, xenon may be regarded as a good candidate for neuroprotectant agent. The hypothalamic region, including the arcuate nucleus–median eminence complex, has been frequently used in studies dealing with glutamate neurotoxicity 19–23 . Indeed, this area appears the most glutamatesensitive among the circumventricular organs where the fenestrated endothelium allows free access to amino acids present in circulating blood.…”

Section: Introductionmentioning

confidence: 99%

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Morphological Evidence that Xenon Neuroprotects against N‐Methyl‐dl‐Aspartic Acid‐Induced Damage in the Rat Arcuate Nucleus

Natale

Cattano

Abramo

et al. 2006

Annals of the New York Academy of Sciences

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The hyperactivation of glutamate receptors, especially those of the N-methyl-d-aspartate subtype (NMDA), can induce excess calcium entry into cells, leading to neuronal death. Since the anesthetic gas xenon behaves as an NMDA antagonist, the present article investigated, by distinct morphological approaches and after different times, the possible neuroprotectant effects of this gas in a model of neuronal damage induced by N-methyl-dl-aspartic acid (NMA) on rat arcuate nucleus. Rats were assigned to the following groups: controls; xenon exposure; NMA treatment; or xenon exposure + NMA treatment. Animals were placed in an experimental cage and after 10 min a mixture of xenon (or nitrogen) 70% and oxygen 30% was delivered. After 3 h, 1, 2, 5, or 7 days from gas exposure, rats were euthanized and the whole brain was removed and processed for either transmission electron microscopy or light microscopy. In the arcuate nucleus from NMA-treated animals only 40-60% of cell population survived in all times with several degenerating neurons giving the typical appearance of a "bull's eye." At ultrastructural level, chromatin margination, nuclear shrinkage, mitochondria with matrix dilution, dilated endoplasmic cisternae, and electrondense cytoplasm were detected. Xenon alone did not induce changes, but reduced of about 50% NMA-induced cell loss as well as degenerating neurons, with the maximal neuroprotection at 7 days. These results confirm that in the rat arcuate nucleus NMA can induce a severe neuronal damage that is already marked after 3 h. Xenon significantly reduced the neuronal damage at all times and can be then regarded as a promising neuroprotectant agent.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Morphological Evidence that Xenon Neuroprotects against N‐Methyl‐dl‐Aspartic Acid‐Induced Damage in the Rat Arcuate Nucleus

Natale

Cattano

Abramo

et al. 2006

Annals of the New York Academy of Sciences

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“…Administering Glu to newborn rodents at 2-4 mg/g BW results in complete destruction of the arcuate nucleus (AN) neurons 9 , and damages a number of other hypothalamic nuclei. Transporter proteins guarantee removal of Glu from the extracellular fluid and long-term maintenance of low and non-toxic concentrations in the central nervous system (CNS).…”

Section: Physiological Considerationsmentioning

confidence: 99%

Does High Glutamate Intake Cause Obesity?

Hermanussen¹,

Tresguerres²

2003

Journal of Pediatric Endocrinology and Metabolism

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World-wide obesity has risen to alarming levels. The average weight of German conscripts now increases by almost 400 g/year. Similar data were obtained in Austria, Norway and the UK. The rising prevalence of obesity coincides with a rising popularity of protein-rich diets. On average, Germans consume meat at 100 kg/year. Children eat some threefold more protein than recommended; infants of 6 to 12 months receive daily up to 5 g/kg body weight of protein. We hypothesise that it is not the protein, but the amino acid glutamate that determines the propensity of obesity. Chronic hyperglutamataemia may intoxicate arcuate nucleus (AN) neurons, thereby disrupting the hypothalamic signalling cascade of leptin action, causing hyperphagia, obesity and hyperleptinaemia. Hyperleptinaemia also exerts sympathetic effects including blood pressure elevation that are mediated via mechanisms different from the hypothalamic system, and other symptoms of the 'metabolic syndrome'. This may happen even before birth when in small-for-gestationalage foetuses with impaired umbilical plasma flow, foetal hyperglutamataemia induces AN damage followed by later impairment of feeding regulation, hyperleptinaemia and symptoms that characterise the 'thrifty phenotype'. We suggest abandoning the flavouring agent monosodium glutamate and reconsidering the recommended daily allowances of protein and amino acids, particularly during pregnancy.

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“…The N-methyl-D-aspartate receptor (NMDA-R) is fully functional in the rat early in embryogenesis. Xue et al (1997) found that GLU-and aspartate-immunoreactive neurones were completely absent in the monosodium glutamate (MSG)-lesioned arcuate nucleus as well as the ventromedial nucleus lateral to the arcuate nucleus, in mice treated neonatally with MSG. Similarly, NMDA-R1-immunoreactive neurones were mostly absent in the MSG-lesioned arcuate nucleus but remained intact in the ventromedial nucleus.…”

Section: Introductionmentioning

confidence: 99%

Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite

Hermanussen¹,

García

Sunder³

et al. 2005

Eur J Clin Nutr

108

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Background: World-wide obesity has risen to alarming levels. We present experimental support for a new and very challenging hypothesis linking obesity, voracity, and growth hormone (GH) deficiency, to the consumption of elevated amounts of the amino-acid glutamate (GLU). Supraphysiological doses of GLU are toxic for neuronal cells. Methods: Human data were obtained from 807 592 German conscripts born between 1974 and 1978, and from 1 432 368 women of the German birth statistics (deutsche Perinatalerhebung) 1995-1997. The effects of orally administered monosodium glutamate (MSG) were investigated in 30 pregnant Wistar rats and their offspring. Pregnant animals either received no extra MSG, or 2.5 g MSG, or 5 g MSG per day, up to the end of the weaning period. In all, 2.5 g, respectively 5 g, MSG accounted for some 10%, respectively 20%, of dry weight of the average daily food ration. After weaning, MSG feeding was continued in the offspring. Findings: Morbid obesity associates with short stature. Average stature of conscripts progressively declines when body mass index increases above 38 kg/m 2 . Also morbidly obese young women are shorter than average though to a lesser extent than conscripts. Oral administration of MSG to pregnant rats affects birth weight of the offspring. Maternal feeding with 5 g MSG per day results in severe birth weight reduction (Po0.01). Weight increments remain subnormal when MSG feeding to the mothers is maintained during weaning (Po0.01). GH serum levels are affected in animals that received MSG during prenatal life via maternal feeding. Animals that are kept on high MSG diet (5 g MSG per day) continue to show serum GH levels that are as low or even lower than those of MSG injected animals (Po0.05), both at day 30 and at day 90 of life. Animals that were kept on medium MSG diet (2.5 g MSG per day) showed low serum GH levels at day 30 of life (Po0.01), but seemed to partially recover before day 90. Almost identical results were observed in IGF-1 serum levels. Oral MSG resulted in dose dependent voracity. The animals fed 5 g MSG per day increased water uptake by threefold (Po0.01), and food uptake by almost two-fold (Po0.01). The influence of MSG is in general more marked in males than in females. Interpretation: GLU is a widely used nutritional substance that potentially exhibits significant neuronal toxicity. Voracity, and impaired GH secretion are the two major characteristics of parenterally administered GLU-induced neuronal damage. GLU maintains its toxicity in animals even when administered orally. Males appear to be more sensitive than females. The present study for the first time demonstrates, that a widely used nutritional monosubstance -the flavouring agent MSG -at concentrations that only slightly surpass those found in everyday human food, exhibits significant potential for damaging the hypothalamic regulation of appetite, and thereby determines the propensity of world-wide obesity. We suggest to reconsider the recommended daily allowances of amino acids and nutritional prot...

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Nitric oxide synthase-, N -methyl- d -aspartate receptor-, glutamate- and aspartate-immunoreactive neurons in the mouse arcuate nucleus: effects of neonatal treatment with monosodium glutamate

Cited by 14 publications

References 35 publications

Morphological Evidence that Xenon Neuroprotects against N‐Methyl‐dl‐Aspartic Acid‐Induced Damage in the Rat Arcuate Nucleus

Morphological Evidence that Xenon Neuroprotects against N‐Methyl‐dl‐Aspartic Acid‐Induced Damage in the Rat Arcuate Nucleus

Does High Glutamate Intake Cause Obesity?

Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite

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