Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis.

Abstract

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.

• Authors: Nicolette Gouder, Louis Scheurer, Jean-Marc Fritschy, Detlev Boison
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 24 Issue 3 Pg. 692-701 (Jan 21 2004) ISSN: 1529-2401 [Electronic] United States
• PMID: 14736855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A1 Receptor Antagonists
• Anticonvulsants
• Enzyme Inhibitors
• Glial Fibrillary Acidic Protein
• Xanthines
• 5-iodotubercidin
• 1,3-dipropyl-8-cyclopentylxanthine
• Adenosine Kinase
• Tubercidin
• Kainic Acid

Topics

• Action Potentials (drug effects)
• Adenosine A1 Receptor Antagonists
• Adenosine Kinase (antagonists & inhibitors, biosynthesis)
• Animals
• Anticonvulsants (pharmacology)
• Astrocytes (enzymology, pathology)
• Brain (enzymology, pathology)
• Disease Models, Animal
• Disease Progression
• Electroencephalography (drug effects)
• Enzyme Inhibitors (pharmacology)
• Epilepsy, Temporal Lobe (chemically induced, enzymology, pathology)
• Glial Fibrillary Acidic Protein (biosynthesis)
• Hippocampus (enzymology, pathology)
• Immunohistochemistry
• Kainic Acid
• Mice
• Neurons (enzymology, pathology)
• Tubercidin (analogs & derivatives, pharmacology)
• Xanthines (pharmacology)