Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 9 May 1969:
Vol. 164. no. 3880, pp. 719 - 721
DOI: 10.1126/science.164.3880.719

Articles

Brain Lesions, Obesity, and Other Disturbances in Mice Treated with Monosodium Glutamate

John W. Olney 1

1 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium L-glutamate-obesity in mice.
A E Andreazzi, D X Scomparin, F P Mesquita, S L Balbo, C Gravena, J C De Oliveira, W Rinaldi, R M G Garcia, S Grassiolli, and P C F Mathias (2009)
J. Endocrinol. 201, 351-359
   Abstract »    Full Text »    PDF »
'That Won-Ton Soup Headache': The Chinese Restaurant Syndrome, MSG and the Making of American Food, 1968-1980.
I. Mosby (2009)
Soc Hist Med 22, 133-151
   Abstract »    Full Text »    PDF »
Specific Targeting of Pro-Death NMDA Receptor Signals with Differing Reliance on the NR2B PDZ Ligand.
F. X. Soriano, M.-A. Martel, S. Papadia, A. Vaslin, P. Baxter, C. Rickman, J. Forder, M. Tymianski, R. Duncan, M. Aarts, et al. (2008)
J. Neurosci. 28, 10696-10710
   Abstract »    Full Text »    PDF »
Hypothalamic neurodegeneration and adult-onset obesity in mice lacking the Ubb polyubiquitin gene.
K.-Y. Ryu, J. C. Garza, X.-Y. Lu, G. S. Barsh, and R. R. Kopito (2008)
PNAS 105, 4016-4021
   Abstract »    Full Text »    PDF »
Food deprivation-induced changes in body fat mobilization after neonatal monosodium glutamate treatment.
C. Leitner and T. J. Bartness (2008)
Am J Physiol Regulatory Integrative Comp Physiol 294, R775-R783
   Abstract »    Full Text »    PDF »
Leptin Sensitivity in the Developing Rat Hypothalamus.
A.-S. Carlo, M. Pyrski, C. Loudes, A. Faivre-Baumann, J. Epelbaum, L. M. Williams, and W. Meyerhof (2007)
Endocrinology 148, 6073-6082
   Abstract »    Full Text »    PDF »
Extensive Gut Metabolism Limits the Intestinal Absorption of Excessive Supplemental Dietary Glutamate Loads in Infant Pigs.
M. J. Janeczko, B. Stoll, X. Chang, X. Guan, and D. G. Burrin (2007)
J. Nutr. 137, 2384-2390
   Abstract »    Full Text »    PDF »
Compartmentalized NMDA receptor signalling to survival and death.
F. X. Soriano and G. E. Hardingham (2007)
J. Physiol. 584, 381-387
   Abstract »    Full Text »    PDF »
Undernutrition in Utero Augments Systolic Blood Pressure and Cardiac Remodeling in Adult Mouse Offspring: Possible Involvement of Local Cardiac Angiotensin System in Developmental Origins of Cardiovascular Disease.
M. Kawamura, H. Itoh, S. Yura, H. Mogami, S.-I. Suga, H. Makino, Y. Miyamoto, Y. Yoshimasa, N. Sagawa, and S. Fujii (2007)
Endocrinology 148, 1218-1225
   Abstract »    Full Text »    PDF »
Roles of Volume-Sensitive Chloride Channel in Excitotoxic Neuronal Injury.
H. Inoue and Y. Okada (2007)
J. Neurosci. 27, 1445-1455
   Abstract »    Full Text »    PDF »
Mitoenergetic failure in Alzheimer disease.
M. S Parihar and G. J. Brewer (2007)
Am J Physiol Cell Physiol 292, C8-C23
   Abstract »    Full Text »    PDF »
Peripheral ghrelin deepens torpor bouts in mice through the arcuate nucleus neuropeptide Y signaling pathway.
E. F. Gluck, N. Stephens, and S. J. Swoap (2006)
Am J Physiol Regulatory Integrative Comp Physiol 291, R1303-R1309
   Abstract »    Full Text »    PDF »
Synergistic Interactions between Commonly Used Food Additives in a Developmental Neurotoxicity Test.
K. Lau, W. G. McLean, D. P. Williams, and C. V. Howard (2006)
Toxicol. Sci. 90, 178-187
   Abstract »    Full Text »    PDF »
MTH1, an Oxidized Purine Nucleoside Triphosphatase, Suppresses the Accumulation of Oxidative Damage of Nucleic Acids in the Hippocampal Microglia during Kainate-Induced Excitotoxicity.
K. Kajitani, H. Yamaguchi, Y. Dan, M. Furuichi, D. Kang, and Y. Nakabeppu (2006)
J. Neurosci. 26, 1688-1698
   Abstract »    Full Text »    PDF »
Hormonal Regulation of Food Intake.
S. Stanley, K. Wynne, B. McGowan, and S. Bloom (2005)
Physiol Rev 85, 1131-1158
   Abstract »    Full Text »    PDF »
TRPM7 and Ischemic CNS Injury.
M. M. Aarts and M. Tymianski (2005)
Neuroscientist 11, 116-123
   Abstract »    PDF »
Minireview: Leptin and Development of Hypothalamic Feeding Circuits.
S. G. Bouret and R. B. Simerly (2004)
Endocrinology 145, 2621-2626
   Abstract »    Full Text »    PDF »
The Nature of Human Hazards Associated with Excessive Intake of Amino Acids.
P. J. Garlick (2004)
J. Nutr. 134, 1633S-1639S
   Abstract »    Full Text »    PDF »
Neural transplantation in hypogonadal (hpg) mice - physiology and neurobiology.
H. Charlton (2004)
Reproduction 127, 3-12
   Abstract »    Full Text »    PDF »
Monosodium Glutamate-Sensitive Hypothalamic Neurons Contribute to the Control of Bone Mass.
F. Elefteriou, S. Takeda, X. Liu, D. Armstrong, and G. Karsenty (2003)
Endocrinology 144, 3842-3847
   Abstract »    Full Text »    PDF »
Role of PPAR-{gamma} Ligands In Neuroprotection against Glutamate-Induced Cytotoxicity in Retinal Ganglion Cells.
P. Aoun, J. W. Simpkins, and N. Agarwal (2003)
Invest. Ophthalmol. Vis. Sci. 44, 2999-3004
   Abstract »    Full Text »    PDF »
Orexin Excites GABAergic Neurons of the Arcuate Nucleus by Activating the Sodium--Calcium Exchanger.
D. Burdakov, B. Liss, and F. M. Ashcroft (2003)
J. Neurosci. 23, 4951-4957
   Abstract »    Full Text »    PDF »
Functional Hemichannels in Astrocytes: A Novel Mechanism of Glutamate Release.
Z.-C. Ye, M. S. Wyeth, S. Baltan-Tekkok, and B. R. Ransom (2003)
J. Neurosci. 23, 3588-3596
   Abstract »    Full Text »    PDF »
Estrogen Receptor-Mediated Neuroprotection from Oxidative Stress Requires Activation of the Mitogen-Activated Protein Kinase Pathway.
A. L. Mize, R. A. Shapiro, and D. M. Dorsa (2003)
Endocrinology 144, 306-312
   Abstract »    Full Text »    PDF »
Neuroprotective and neurotoxic properties of the 'inert' gas, xenon.
D. Ma, S. Wilhelm, M. Maze, and N. P. Franks (2002)
Br. J. Anaesth. 89, 739-746
   Abstract »    Full Text »    PDF »
Determinants Affecting Physical Activity Levels In Animal Models.
J. C.L. Tou and C. E. Wade (2002)
Experimental Biology and Medicine 227, 587-600
   Abstract »    Full Text »    PDF »
MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure.
C. Schoelch, T. Hubschle, I. Schmidt, and B. Nuesslein-Hildesheim (2002)
Am J Physiol Endocrinol Metab 283, E604-E611
   Abstract »    Full Text »    PDF »
Light-Dependent Induction of cFos during Subjective Day and Night in PACAP-Containing Ganglion Cells of the Retinohypothalamic Tract.
J. Hannibal, N. Vrang, J. P. Card, and J. Fahrenkrug (2001)
J Biol Rhythms 16, 457-470
   Abstract »    PDF »
Sindbis Virus-Induced Neuronal Death Is both Necrotic and Apoptotic and Is Ameliorated by N-Methyl-D-Aspartate Receptor Antagonists.
J. L. Nargi-Aizenman and D. E. Griffin (2001)
J. Virol. 75, 7114-7121
   Abstract »    Full Text »
Glutamate antagonists: Deadly liaisons with cancer.
E. A. Cavalheiro and J. W. Olney (2001)
PNAS 98, 5947-5948
   Full Text »    PDF »
How Protein Kinase C Activation Protects Nerve Cells from Oxidative Stress-Induced Cell Death.
P. Maher (2001)
J. Neurosci. 21, 2929-2938
   Abstract »    Full Text »    PDF »
Glutamate Transporters in Neurologic Disease.
N. J. Maragakis and J. D. Rothstein (2001)
Arch Neurol 58, 365-370
   Full Text »    PDF »
Disruption of Arcuate/Paraventricular Nucleus Connections Changes Body Energy Balance and Response to Acute Stress.
M. E. Bell, S. Bhatnagar, S. F. Akana, S. Choi, and M. F. Dallman (2000)
J. Neurosci. 20, 6707-6713
   Abstract »    Full Text »    PDF »
Solitary Tract Nuclei in Acute Heart Failure.
Raffaele De Caro, A. Parenti, M. Montisci, D. Guidolin, and V. Macchi (2000)
Stroke 31, 1187-1193
   Abstract »    Full Text »    PDF »
Pituitary Hormone Secretion in Normal Male Humans: Acute Responses to a Large, Oral Dose of Monosodium Glutamate.
J. D. Fernstrom (2000)
J. Nutr. 130, 1053
   Abstract »    Full Text »
Expression of Ciliary Neurotrophic Factor Activated by Retinal Muller Cells in Eyes with NMDA- and Kainic Acid-Induced Neuronal Death.
M. Honjo, H. Tanihara, N. Kido, M. Inatani, K. Okazaki, and Y. Honda (2000)
Invest. Ophthalmol. Vis. Sci. 41, 552-560
   Abstract »    Full Text »
Central Administration of Cocaine-Amphetamine-Regulated Transcript Activates Hypothalamic Neuroendocrine Neurons in the Rat.
N. Vrang, P. J. Larsen, P. Kristensen, and M. Tang-Christensen (2000)
Endocrinology 141, 794-801
   Abstract »    Full Text »    PDF »
Mitochondria and Neuronal Survival.
D. G. Nicholls and S. L. Budd (2000)
Physiol Rev 80, 315-360
   Abstract »    Full Text »    PDF »
Current and Potential Drugs for Treatment of Obesity.
G. A. Bray and F. L. Greenway (1999)
Endocr. Rev. 20, 805-875
   Abstract »    Full Text »
Alteration of the Leptin Network in Late Morbid Obesity Induced in Mice by Brain Infection with Canine Distemper Virus.
A. Bernard, R. Cohen, S.-T. Khuth, B. Vedrine, O. Verlaeten, H. Akaoka, P. Giraudon, and M.-F. Belin (1999)
J. Virol. 73, 7317-7327
   Abstract »    Full Text »
Agouti-Related Protein Containing Nerve Terminals Innervate Thyrotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus.
G. Légrádi and R. M. Lechan (1999)
Endocrinology 140, 3643-3652
   Abstract »    Full Text »
The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice.
C. Broberger, J. Johansen, C. Johansson, M. Schalling, and T. Hokfelt (1998)
PNAS 95, 15043-15048
   Abstract »    Full Text »    PDF »
Obesity and Insulin Resistance in Human Growth Hormone Transgenic Rats.
A. Ikeda, K.-T. Chang, Y. Matsumoto, Y. Furuhata, M. Nishihara, F. Sasaki, and M. Takahashi (1998)
Endocrinology 139, 3057-3063
   Abstract »    Full Text »    PDF »
The Arcuate Nucleus Is the Major Source for Neuropeptide Y-Innervation of Thyrotropin-Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus.
G. Legradi and R. M. Lechan (1998)
Endocrinology 139, 3262-3270
   Abstract »    Full Text »    PDF »
Topical Review: Glutamate in Neurologic Diseases.
P. Bittigau and C. Ikonomidou (1997)
J Child Neurol 12, 471-485
   Abstract »    PDF »
Overexpression of CuZn-Superoxide Dismutase Reduces Hippocampal Injury After Global Ischemia in Transgenic Mice.
K. Murakami, T. Kondo, C. J. Epstein, and P. H. Chan (1997)
Stroke 28, 1797-1804
   Abstract »    Full Text »
Amino Acid Neurotransmission and Initiation of Puberty: Evidence from Nonketotic Hyperglycinemia in a Female Infant and Gonadotropin-Releasing Hormone Secretion by Rat Hypothalamic Explants.
J.-P. Bourguignon, J. Jaeken, A. Gerard, and F. de Zegher (1997)
J. Clin. Endocrinol. Metab. 82, 1899-1903
   Abstract »    Full Text »    PDF »
Selective N-Type Calcium Channel Antagonist Omega Conotoxin MVIIA Is Neuroprotective Against Hypoxic Neurodegeneration in Organotypic Hippocampal-Slice Cultures.
A.K. Pringle, C.D. Benham, L. Sim, J. Kennedy, F. Iannotti, L.E. Sundstrom, and D. W. Choi (1996)
Stroke 27, 2124-2130
   Abstract »    Full Text »
The Role of Monoamine Metabolism in Oxidative Glutamate Toxicity.
P. Maher and J. B. Davis (1996)
J. Neurosci. 16, 6394-6401
   Abstract »    Full Text »    PDF »
Ischemic Delayed Neuronal Death : A Mitochondrial Hypothesis.
K. Abe, M. Aoki, J. Kawagoe, T. Yoshida, A. Hattori, K. Kogure, and Y. Itoyama (1995)
Stroke 26, 1478-1489
   Abstract »    Full Text »
Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia.
C. K. Rokkas, C. S. Cronin, T. Nitta, L. R. Helfrich Jr., D. C. Lobner, D. W. Choi, and N. T. Kouchoukos (1995)
J. Thorac. Cardiovasc. Surg. 110, 27-35
   Abstract »    Full Text »
REVIEW {blacksquare} : Neuroprotection in Brain Ischemia: An Update (Part I.
M. D. Ginsberg (1995)
Neuroscientist 1, 95-103
   Abstract »    PDF »
Excitatory Amino Acids in Neurologic Disorders.
A. Samuels, S. Seifter, S. A. Lipton, and P. A. Rosenberg (1994)
N. Engl. J. Med. 331, 274-275
   Full Text »
Supplemental Alanylglutamine, Organ Growth, and Nitrogen Metabolism in Neonatal Pigs Fed by Total Parenteral Nutrition.
D. G. Burrin, R. J. Shulman, C. Langston, and M. C. Storm (1994)
JPEN J Parenter Enteral Nutr 18, 313-319
   Abstract »    PDF »
Targeted expression of a toxin gene to adipose tissue: transgenic mice resistant to obesity..
S R Ross, R A Graves, and B M Spiegelman (1993)
Genes & Dev. 7, 1318-1324
   Abstract »    PDF »
Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.
G. Hotamisligil, N. Shargill, and B. Spiegelman (1993)
Science 259, 87-91
   Abstract »    PDF »
Glutamate, a Neurotoxic Transmitter.
J. W. Olney (1989)
J Child Neurol 4, 218-226
   PDF »
Glutamate Antagonist Therapy Reduces Neurologic Deficits Produced by Focal Central Nervous System Ischemia.
A. Kochhar, J. A. Zivin, P. D. Lyden, and V. Mazzarella (1988)
Arch Neurol 45, 148-153
   Abstract »    PDF »
Severely impaired adipsin expression in genetic and acquired obesity.
J. Flier, K. Cook, P Usher, and B. Spiegelman (1987)
Science 237, 405-408
   Abstract »    PDF »
Perinatal exposure to cannabinoids alters male reproductive function in mice.
S Dalterio and A Bartke (1979)
Science 205, 1420-1422
   Abstract »    PDF »
alpha-Melanocyte-stimulating hormone: reduction in adult rat brain after monosodium glutamate treatment of neonates.
R. Eskay, M. Brownstein, and R. Long (1979)
Science 205, 827-829
   Abstract »    PDF »
Axon-sparing brain lesioning technique: the use of monosodium-L-glutamate and other amino acids.
E. Simson, R. Gold, L. Standish, and P. Pellett (1977)
Science 198, 515-517
   Abstract »    PDF »
Monosodium glutamate admlinistration to the newborn reduces reproductive ability in female and male mice.
W. Pizzi, J. Barnhart, and D. Fanslow (1977)
Science 196, 452-454
   Abstract »    PDF »
Saltiness of Monosodium Glutamate And Sodium Intake.
L. M. Bartoshuk, W. S. Cain, C. T. Cleveland, L. S. Grossman, L. E. Marks, J. C. Stevens, and J. A. J. Stolwijk (1974)
JAMA 230, 670
   Abstract »    PDF »
Clinical Features of the Lesch-Nyhan Syndrome.
W. L. Nyhan (1972)
Arch Intern Med 130, 186-192
   Abstract »    PDF »
Monosodium Glutamate: Absence of Hypothalamic Lesions after Ingestion by Newborn Primates.
W. A. Reynolds, N. Lemkey-Johnston, L. J. Filer Jr., and R. M. Pitkin (1971)
Science 172, 1342-1344
   Abstract »    PDF »
Monosodium Glutamate-Induced Brain Lesions: Electron Microscopic Examination.
E. A. Arees and J. Mayer (1970)
Science 170, 549-550
   Abstract »    PDF »
Monosodium Glutamate: Feeding of Large Amounts in Man and Gerbils.
G. Bazzano, J. A. D'Elia, and R. E. Olson (1970)
Science 169, 1208-1209
   Abstract »    PDF »
Monosodium Glutamate: Lack of Effects on Brain and Reproductive Function in Rats.
N. J. Adamo and A. Ratner (1970)
Science 169, 673-674
   Abstract »    PDF »
Brain Lesions in an Infant Rhesus Monkey Treated with Monosodium Glutamate.
J. W. Olney and L. G. Sharpe (1969)
Science 166, 386-388
   Abstract »    PDF »
Monosodium Glutamate.
F. R. Blood, B. L. Oser, P. L. White, and J. W. Olney (1969)
Science 165, 1028-1029
   PDF »
Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes.
T. Imai, M. Jiang, P. Chambon, and D. Metzger (2001)
PNAS 98, 224-228
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)