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James O. McNamara1,2,3*,,
Yang Zhong Huang1,, and
A. Soren Leonard1,
1Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. 2Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA. 3Center for Translational Neuroscience, Duke University Medical Center, Durham, NC 27710, USA. These authors contributed equally to this work.
Gloss: The epilepsies, disorders of recurrent seizures, affect about 1% of the population worldwide. Available therapy is symptomatic in that drugs inhibit seizures but are not disease-modifying; that is, no effective pharmacological prevention or cure has been identified. The term "epileptogenesis" refers to the process by which a normal brain becomes epileptic. Understanding the cellular mechanisms of epileptogenesis in molecular terms may help identify molecular targets for which small-molecule therapeutics can be developed to prevent epileptogenesis in individuals at high risk. A number of acquired and genetic causes of this disorder have been identified, and various in vivo and in vitro models of epileptogenesis have been established. The objective of this STKE Review, with 5 figures, 2 tables, and 199 references, is to review current insights into the molecular signaling mechanisms underlying epileptogenesis, focusing on limbic epileptogenesis in particular.
Sharon A. Meyer and Randy L. Jirtle (7 May 2013) Sci. Signal.6 (274), pe16.
[DOI: 10.1126/scisignal.2004239] |Abstract »|Full Text »|PDF »
EDITORS' CHOICE
John F. Foley (13 April 2010) Sci. Signal.3 (117), ec111.
[DOI: 10.1126/scisignal.3117ec111] |Abstract »
EDITORS' CHOICE
Elizabeth M. Adler (25 August 2009) Sci. Signal.2 (85), ec284.
[DOI: 10.1126/scisignal.285ec284] |Abstract »
PERSPECTIVES
Hao Wu and Yi Eve Sun (31 March 2009) Sci. Signal.2 (64), pe17.
[DOI: 10.1126/scisignal.264pe17] |Abstract »|Full Text »|PDF »
EDITORIAL GUIDES
Elizabeth M. Adler (10 October 2006) Sci. STKE2006 (356), eg11.
[DOI: 10.1126/stke.3562006eg11] |Abstract »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy.
M. Cammarota, G. Losi, A. Chiavegato, M. Zonta, and G. Carmignoto (2013)
J. Physiol.
591, 807-822
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J. Neurosci.
32, 17800-17812
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Heterogeneous firing behavior during ictal-like epileptiform activity in vitro.
NMDA receptors regulate GABAA receptor lateral mobility and clustering at inhibitory synapses through serine 327 on the {gamma}2 subunit.
J. Muir, I. L. Arancibia-Carcamo, A. F. MacAskill, K. R. Smith, L. D. Griffin, and J. T. Kittler (2010)
PNAS
107, 16679-16684
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Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage.
H. Parfenova, C. W. Leffler, D. Tcheranova, S. Basuroy, and A. Zimmermann (2010)
Am J Physiol Heart Circ Physiol
298, H1687-H1698
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Mutual Regulation of Src Family Kinases and the Neurotrophin Receptor TrkB.
BC1 Regulation of Metabotropic Glutamate Receptor-Mediated Neuronal Excitability.
J. Zhong, S.-C. Chuang, R. Bianchi, W. Zhao, H. Lee, A. A. Fenton, R. K. S. Wong, and H. Tiedge (2009)
J. Neurosci.
29, 9977-9986
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Cellular Plasticity for Group I mGluR-Mediated Epileptogenesis.
R. Bianchi, S.-C. Chuang, W. Zhao, S. R. Young, and R. K. S. Wong (2009)
J. Neurosci.
29, 3497-3507
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Characterization of an epilepsy-associated variant of the human Cl-/HCOFormula exchanger AE3.
G. L. Vilas, D. E. Johnson, P. Freund, and J. R. Casey (2009)
Am J Physiol Cell Physiol
297, C526-C536
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BDNF Selectively Regulates GABAA Receptor Transcription by Activation of the JAK/STAT Pathway.
I. V. Lund, Y. Hu, Y. H. Raol, R. S. Benham, R. Faris, S. J. Russek, and A. R. Brooks-Kayal (2008)
Science Signaling
1, ra9
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Early Alterations of AMPA Receptors Mediate Synaptic Potentiation Induced by Neonatal Seizures.
S. N. Rakhade, C. Zhou, P. K. Aujla, R. Fishman, N. J. Sucher, and F. E. Jensen (2008)
J. Neurosci.
28, 7979-7990
|Abstract »|Full Text »|PDF »
Regulation of synaptic inhibition by phospho-dependent binding of the AP2 complex to a YECL motif in the GABAA receptor {gamma}2 subunit.
J. T. Kittler, G. Chen, V. Kukhtina, A. Vahedi-Faridi, Z. Gu, V. Tretter, K. R. Smith, K. McAinsh, I. L. Arancibia-Carcamo, W. Saenger, et al. (2008)
PNAS
105, 3616-3621
|Abstract »|Full Text »|PDF »