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

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Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice.

Astrogliosis is a pathological hallmark of the epileptic brain. The identification of mechanisms that link astrogliosis to neuronal dysfunction in epilepsy may provide new avenues for therapeutic intervention. Here we show that astrocyte-expressed adenosine kinase (ADK), a key negative regulator of the brain inhibitory molecule adenosine, is a potential predictor and modulator of epileptogenesi...

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Traditionally, epilepsy has been considered to be a disorder of neuronal dysfunction. Based on this dogma, drug development efforts have largely focused on neurocentric model systems to screen for compounds that affect the function of neurons. Unfortunately, about 30% of all patients with epilepsy - or more than 20 million worldwide - are refractory to classical neurocentric pharmacotherapy. Th...

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Overexpression of adenosine kinase in epileptic hippocampus contributes to epileptogenesis.

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-induc...

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Astrogliosis in epilepsy leads to overexpression of adenosine kinase, resulting in seizure aggravation.

Adenosine kinase (ADK) is considered to be the key regulator of the brain's endogenous anticonvulsant, adenosine. In adult brain, ADK is primarily expressed in a subpopulation of astrocytes and striking upregulation of ADK in these cells has been associated with astrogliosis after kainic acid-induced status epilepticus (KASE) in the kainic acid mouse model of temporal lobe epilepsy. To investig...

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ژورنال

عنوان ژورنال: Neuron Glia Biology

سال: 2008

ISSN: 1740-925X,1741-0533

DOI: 10.1017/s1740925x09990135