| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Animal Model |
From the Neuroinflammation Research Laboratories of the Department
of Psychiatry,
and the Brookdale Center for
Developmental and Molecular Biology,*
Mount Sinai School of
Medicine, New York, New York; the Department of
Inflammation,
Roche-Bioscience, Palo Alto,
California; and the Department of Neurology,§
Georgetown University School of Medicine, Washington, D.C.
In this study we describe the generation of a transgenic mouse model with neuronal overexpression of the human cyclooxygenase-2, h(COX)-2, to explore its role in excitotoxicity. We report that overexpression of neuronal hCOX-2 potentiates the intensity and lethality of kainic acid excitotoxicity in coincidence with potentiation of expression of the immediate early genes c-fos and zif-268. In vitro studies extended the in vivo findings and revealed that glutamate excitotoxicity is potentiated in primary cortico-hippocampal neurons derived from hCOX-2 transgenic mice, possibly through potentiation of mitochondrial impairment. This study is the first to demonstrate a cause-effect relationship between neuronal COX-2 expression and excitotoxicity. This model system will allow the systematic examination of the role of COX-2 in mechanisms of neurodegeneration that involve excitatory amino acid pathways.
This article has been cited by other articles:
 |
|
 |
|
  J. V. Gardiner, A. Bataveljic, N. A. Patel, G. A. Bewick, D. Roy, D. Campbell, H. C. Greenwood, K. G. Murphy, S. Hameed, P. H. Jethwa, et al. Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake Diabetes, February 1, 2010; 59(2): 397 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Sharma, G. H. Searfoss, R. Y. Reams, W. H. Jordan, P. W. Snyder, A. Y. Chiang, R. A. Jolly, and T. P. Ryan Kainic Acid-induced F-344 Rat model of Mesial Temporal Lobe Epilepsy: Gene Expression and Canonical Pathways Toxicol Pathol, October 1, 2009; 37(6): 776 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Qin, V. Haroutunian, P. Katsel, C. P. Cardozo, L. Ho, J. D. Buxbaum, and G. M. Pasinetti PGC-1{alpha} Expression Decreases in the Alzheimer Disease Brain as a Function of Dementia Arch Neurol, March 1, 2009; 66(3): 352 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. X. Albuquerque, E. F. R. Pereira, M. Alkondon, and S. W. Rogers Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function Physiol Rev, January 1, 2009; 89(1): 73 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ma, R. Langenbach, S. I. Rapoport, and M. Basselin Altered brain lipid composition in cyclooxygenase-2 knockout mouse J. Lipid Res., April 1, 2007; 48(4): 848 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Hewett, J. M. Silakova, and J. A. Hewett Oral Treatment with Rofecoxib Reduces Hippocampal Excitotoxic Neurodegeneration J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1219 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sang and C. Chen Lipid Signaling and Synaptic Plasticity Neuroscientist, October 1, 2006; 12(5): 425 - 434. [Abstract] [PDF]
|
|
|
|
 |
|
 W. Qin, T. Yang, L. Ho, Z. Zhao, J. Wang, L. Chen, W. Zhao, M. Thiyagarajan, D. MacGrogan, J. T. Rodgers, et al. Neuronal SIRT1 Activation as a Novel Mechanism Underlying the Prevention of Alzheimer Disease Amyloid Neuropathology by Calorie Restriction J. Biol. Chem., August 4, 2006; 281(31): 21745 - 21754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Simmons, R. M. Botting, and T. Hla Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition Pharmacol. Rev., September 1, 2004; 56(3): 387 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Silakova, J. A. Hewett, and S. J. Hewett Naproxen Reduces Excitotoxic Neurodegeneration in Vivo with an Extended Therapeutic Window J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1060 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Qin, L. Ho, P. N. Pompl, Y. Peng, Z. Zhao, Z. Xiang, N. K. Robakis, J. Shioi, J. Suh, and G. M. Pasinetti Cyclooxygenase (COX)-2 and COX-1 Potentiate {beta}-Amyloid Peptide Generation through Mechanisms That Involve {gamma}-Secretase Activity J. Biol. Chem., December 19, 2003; 278(51): 50970 - 50977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Mizuno, K. A. Kelley, G. M. Pasinetti, J. L. Roberts, and C. V. Mobbs Transgenic Neuronal Expression of Proopiomelanocortin Attenuates Hyperphagic Response to Fasting and Reverses Metabolic Impairments in Leptin-Deficient Obese Mice Diabetes, November 1, 2003; 52(11): 2675 - 2683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Li, B. W. Row, E. Gozal, L. Kheirandish, Q. Fan, K. R. Brittian, S. Z. Guo, L. R. Sachleben Jr., and D. Gozal Cyclooxygenase 2 and Intermittent Hypoxia-induced Spatial Deficits in the Rat Am. J. Respir. Crit. Care Med., August 15, 2003; 168(4): 469 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Salzberg-Brenhouse, E.-Y. Chen, D. F. Emerich, S. Baldwin, K. Hogeland, S. Ranelli, D. Lafreniere, B. Perdomo, L. Novak, T. Kladis, et al. Inhibitors of Cyclooxygenase-2, but Not Cyclooxygenase-1 Provide Structural and Functional Protection against Quinolinic Acid-Induced Neurodegeneration J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 218 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Acarin, B. Gonzalez, and B. Castellano Decrease of Proinflammatory Molecules Correlates With Neuroprotective Effect of the Fluorinated Salicylate Triflusal After Postnatal Excitotoxic Damage Stroke, October 1, 2002; 33(10): 2499 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ciceri, Y. Zhang, A. F. Shaffer, K. M. Leahy, M. B. Woerner, W. G. Smith, K. Seibert, and P. C. Isakson Pharmacology of Celecoxib in Rat Brain after Kainate Administration J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 846 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Basu, J. K. Krady, M. O'Malley, S. D. Styren, S. T. DeKosky, and S. W. Levison The Type 1 Interleukin-1 Receptor Is Essential for the Efficient Activation of Microglia and the Induction of Multiple Proinflammatory Mediators in Response to Brain Injury J. Neurosci., July 15, 2002; 22(14): 6071 - 6082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mirjany, L. Ho, and G. M. Pasinetti Role of Cyclooxygenase-2 in Neuronal Cell Cycle Activity and Glutamate-Mediated Excitotoxicity J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 494 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. I. Andreasson, A. Savonenko, S. Vidensky, J. J. Goellner, Y. Zhang, A. Shaffer, W. E. Kaufmann, P. F. Worley, P. Isakson, and A. L. Markowska Age-Dependent Cognitive Deficits and Neuronal Apoptosis in Cyclooxygenase-2 Transgenic Mice J. Neurosci., October 15, 2001; 21(20): 8198 - 8209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ho, D. Purohit, V. Haroutunian, J. D. Luterman, F. Willis, J. Naslund, J. D. Buxbaum, R. C. Mohs, P. S. Aisen, and G. M. Pasinetti Neuronal Cyclooxygenase 2 Expression in the Hippocampal Formation as a Function of the Clinical Progression of Alzheimer Disease Arch Neurol, March 1, 2001; 58(3): 487 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Iadecola, K. Niwa, S. Nogawa, X. Zhao, M. Nagayama, E. Araki, S. Morham, and M. E. Ross Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice PNAS, January 30, 2001; 98(3): 1294 - 1299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Petersen, S. Petersen, L. Milas, F. F. Lang, and P. J. Tofilon Enhancement of Intrinsic Tumor Cell Radiosensitivity Induced by a Selective Cyclooxygenase-2 Inhibitor Clin. Cancer Res., June 1, 2000; 6(6): 2513 - 2520. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
