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Uncoupling of astrogliosis from epileptogenesis in adenosine kinase (ADK) transgenic mice

Published online by Cambridge University Press:  13 August 2009

Tianfu Li ,
Jing-Quan Lan  and
Detlev Boison
Tianfu Li
Affiliation:
R. S. Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
Jing-Quan Lan
Affiliation:
R. S. Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
Detlev Boison*
Affiliation:
R. S. Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA
*
Correspondence should be addressed to: Detlev Boison, R. S. Dow Neurobiology Laboratories, Legacy Research, Portland, OR 97232, USA phone: (503) 413 1754 fax: (503) 413 5465 email: dboison@downeurobiology.org
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Abstract

The astrocytic enzyme adenosine kinase (ADK) is a key negative regulator of the brain’s endogenous anticonvulsant adenosine. Astrogliosis with concomitant upregulation of ADK is part of the epileptogenic cascade and contributes to seizure generation. To molecularly dissect the respective roles of astrogliosis and ADK-expression for seizure generation, we used a transgenic approach to uncouple ADK-expression from astrogliosis: in Adk-tg mice the endogenous Adk-gene was deleted and replaced by a ubiquitously expressed Adk-transgene with novel ectopic expression in pyramidal neurons, resulting in spontaneous seizures. Here, we followed a unique approach to selectively injure the CA3 of these Adk-tg mice. Using this strategy, we had the opportunity to study astrogliosis and epileptogenesis in the absence of the endogenous astrocytic Adk-gene. After triggering epileptogenesis we demonstrate astrogliosis without upregulation of ADK, but lack of seizures, whereas matching wild-type animals developed astrogliosis with upregulation of ADK and spontaneous recurrent seizures. By uncoupling ADK-expression from astrogliosis, we demonstrate that global expression levels of ADK rather than astrogliosis per se contribute to seizure generation.

Keywords

Astrogliosisseizureskainic acidepileptogenesisCA3
Type
Research Article
Information
Neuron Glia Biology , Volume 4 , Issue 2 , May 2008 , pp. 91 - 99
Copyright
Copyright © Cambridge University Press 2009

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