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The Journal of Neuroscience, January 21, 2004, 24(3):692-701; doi:10.1523/JNEUROSCI.4781-03.2004

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Neurobiology of Disease
Overexpression of Adenosine Kinase in Epileptic Hippocampus Contributes to Epileptogenesis

Nicolette Gouder,¹ Louis Scheurer,¹ Jean-Marc Fritschy,¹ and Detlev Boison^1,2

¹Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland, and ²Department of Chemistry and Applied Biosciences, Federal Institute of Technology (ETH), CH-8057 Zurich, Switzerland

Endogenous adenosine in the brain is thought to prevent the development and spread of seizures via a tonic anticonvulsant effect. Brain levels of adenosine are primarily regulated by the activity of adenosine kinase. To establish a link between adenosine kinase expression and seizure activity, we analyzed the expression of adenosine kinase in the brain of control mice and in a kainic acid-induced mouse model of mesial temporal lobe epilepsy. Immunohistochemical analysis of brain sections of control mice revealed intense staining for adenosine kinase, mainly in astrocytes, which were more or less evenly distributed throughout the brain, as well as in some neurons, particularly in olfactory bulb, striatum, and brainstem. In contrast, hippocampi lesioned by a unilateral kainic acid injection displayed profound astrogliosis and therefore a significant increase in adenosine kinase immunoreactivity accompanied by a corresponding increase of enzyme activity, which paralleled chronic recurrent seizure activity in this brain region. Accordingly, seizures and interictal spikes were suppressed by the injection of a low dose of the adenosine kinase inhibitor 5-iodotubercidin. We conclude that overexpression of adenosine kinase in discrete parts of the epileptic hippocampus may contribute to the development and progression of seizure activity.

Key words: adenosine kinase; adenosine; epilepsy; seizure susceptibility; kainic acid; iodotubercidin

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Received Aug 26, 2003; revised November 17, 2003; accepted November 17, 2003.

This article has been cited by other articles:

				T. Li, J. A. Steinbeck, T. Lusardi, P. Koch, J. Q. Lan, A. Wilz, M. Segschneider, R. P. Simon, O. Brustle, and D. Boison Suppression of kindling epileptogenesis by adenosine releasing stem cell-derived brain implants Brain, May 1, 2007; 130(5): 1276 - 1288. [Abstract] [Full Text] [PDF]

				D. E. Fedele, N. Gouder, M. Guttinger, L. Gabernet, L. Scheurer, T. Rulicke, F. Crestani, and D. Boison Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation Brain, October 1, 2005; 128(10): 2383 - 2395. [Abstract] [Full Text] [PDF]

				D. Boison Adenosine and Epilepsy: From Therapeutic Rationale to New Therapeutic Strategies Neuroscientist, February 1, 2005; 11(1): 25 - 36. [Abstract] [PDF]

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