Adenosine A1 receptor expression in spinal cord in an experimental epilepsy model

GIRARDI E, PICHEL M

Chicago- Estados Unidos

Congreso; Neuroscience Meeting. Society for Neuroscience; 2009

Society for Neuroscience

Adenosine is a neuromodulator which mediates a variety of central functions, such as sedation and pain and acts as an endogenous anticonvulsant. During seizures adenosine levels are increased. Adenosine inhibits glutamate release from neurons and regulates neuronal activity through specific receptors, being adenosine receptor A1R linked to inhibition of adenylate cyclase mediated by G protein, the most abundant of the four kinds of adenosine receptor described. Although the clinical signs associated with epilepsy have the origin in supraspinals structures,  it is the spinal cord responsible of generating the typical tonic clonic contractions associated with seizures. Isolated spinal cord from the brain has convulsive paroxystic motor activity, which is observed in intact animals.  In this work the distribution of adenosine A1 receptors in the spinal cord and the effect of repetitive administration of the convulsant drug 3-mercaptopropiónico acid (MP) have been studied. Methods: Lots of Wistar rats (250-300g) were administered with daily doses of MP, 45mg/kg, i.p., (MP) during seven days. MP induces tonic-clonic seizures. Control rats were injected with saline. One day after last injection rats were anesthetized and perfused extracting the spinal cord of each region and processed for immunohistochemical assays using antiadenosine A1R as primary antibody and peroxidase- antiperoxidase techniques. Results: Immunohistochemical studies showed A1R expression in ventral horn in all regions. Large neurons were positive marked. After MP 7, A1R decreased 76% respect to control in cervical region, 52% in thoracic area and 70% in lumbar area. In dorsal horns dense staining was observed in lamina II and III. A decrease of 35%, 38% and 45% in A1 expression was observed in cervical, thoracic and lumbar area respectively after MP administration. Conclusions: The decreased expression of the receptor A1 in the model of MP repetitive convulsions suggests that adenosine could not be protecting from convusive seizures.