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Altered distribution and function of A2A adenosine receptors in the brain of WAG/Rij rats with genetic absence epilepsy, before and after appearance of the disease
- Source :
- The European journal of neuroscience. 30(6)
- Publication Year :
- 2009
-
Abstract
- The involvement of excitatory adenosine A(2A) receptors (A(2A)Rs), which probably contribute to the pathophysiology of convulsive seizures, has never been investigated in absence epilepsy. Here, we examined the distribution and function of A(2A)Rs in the brain of Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a model of human absence epilepsy in which disease onset occurs 2-3 months after birth. In the cerebral areas that are mostly involved in the generation of absence seizures (somatosensory cortex, reticular and ventrobasal thalamic nuclei), A(2A)R density was lower in presymptomatic WAG/Rij rats than in control rats, as evaluated by immunohistochemistry and western blotting. Accordingly, in cortical/thalamic slices prepared from the brain of these rats, A(2A)R stimulation with the agonist 2-[4-(-2-carboxyethyl)-phenylamino]-5'-N-ethylcarboxamido-adenosine failed to modulate either cAMP formation, mitogen-activated protein kinase system, or K(+)-evoked glutamate release. In contrast, A(2A)R expression, signalling and function were significantly enhanced in brain slices from epileptic WAG/Rij rats as compared with matched control animals. Additionally, the in vivo injection of the A(2A)R agonist CGS21680, or the antagonist 5-amino-7-(2-phenylethyl)-2-(2-fuyl)-pyrazolo-(4,3-c)1,2,4-triazolo(1,5-c)-pyrimidine, in the examined brain areas of epileptic rats, increased and decreased, respectively, the number/duration of recorded spontaneous spike-wave discharges in a dose-dependent manner during a 1-5 h post-treatment period. Our results support the hypothesis that alteration of excitatory A(2A)R is involved in the pathogenesis of absence seizures and might represent a new interesting target for the therapeutic management of this disease.
- Subjects :
- Agonist
Male
medicine.medical_specialty
Adenosine
Microinjections
Receptor, Adenosine A2A
medicine.drug_class
MAP Kinase Signaling System
Blotting, Western
Glutamic Acid
Stimulation
Somatosensory system
Epilepsy
Thalamus
Internal medicine
Phenethylamines
Medicine
Animals
Receptor
Analysis of Variance
business.industry
General Neuroscience
Glutamate receptor
Antagonist
Age Factors
Electroencephalography
Somatosensory Cortex
Triazoles
medicine.disease
Adenosine receptor
Immunohistochemistry
Rats
Disease Models, Animal
Endocrinology
Pyrimidines
Epilepsy, Absence
Disease Progression
business
Subjects
Details
- ISSN :
- 14609568
- Volume :
- 30
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- The European journal of neuroscience
- Accession number :
- edsair.doi.dedup.....82796d331d80a86d185dddcb647ce5e2