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

Iolanda D'Alimonte, Mariagrazia D'Auro, Rita Citraro, Francesca Biagioni, Shucui Jiang, Eleonora Nargi, Silvana Buccella, Patrizia Di Iorio, Patricia Giuliani, Patrizia Ballerini, Francesco Caciagli, Emilio Russo, Giovambattista De Sarro, Renata Ciccarelli

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Abstract

The involvement of excitatory adenosine A2A receptors (A 2ARs), which probably contribute to the pathophysiology of convulsive seizures, has never been investigated in absence epilepsy. Here, we examined the distribution and function of A2ARs 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), A2AR 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, A2AR 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 2AR 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 A2AR 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 A2AR is involved in the pathogenesis of absence seizures and might represent a new interesting target for the therapeutic management of this disease.

Original languageEnglish
Pages (from-to)1023-1035
Number of pages13
JournalEuropean Journal of Neuroscience
Volume30
Issue number6
DOIs
Publication statusPublished - Sep 2009

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Keywords

  • CAMP levels
  • Electroencephalographic (EEG) recordings
  • Glutamate release
  • MAPK system
  • Spike-wave discharge (SWD)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

D'Alimonte, I., D'Auro, M., Citraro, R., Biagioni, F., Jiang, S., Nargi, E., Buccella, S., Di Iorio, P., Giuliani, P., Ballerini, P., Caciagli, F., Russo, E., De Sarro, G., & Ciccarelli, R. (2009). 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. European Journal of Neuroscience, 30(6), 1023-1035. https://doi.org/10.1111/j.1460-9568.2009.06897.x