Abnormalities in A1 and A2A Receptor Binding in the Neocortex of Patients with Frontal Lobe Epilepsy
Abstract number :
1.085
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2021
Submission ID :
1826333
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:53 AM
Authors :
Luisa Rocha, PhD - Centro de Investigación y de Estudios Avanzados; Monserrat Fuentes-Mejia - Pharmacobiology - Centro de Investigación y de Estudios Avanzados; Daniel Fonseca-Barriendos - Pharmacobiology - Centro de Investigación y de Estudios Avanzados; Sandra Orozco-Suarez - Unidad de Investigación Médica en Enfermedades Neurológicas - Hospital de Especialidades del Centro Médico Nacional; Mario Alonso-Vanegas - Hospital HMG
Rationale: A1 and A2A adenosine receptors induce inhibitory and excitatory effects, respectively. Changes in A1 and A2A receptors have been found in brain tissue obtained from patients with temporal lobe epilepsy, the most common type of epilepsy. Although frontal lobe epilepsy (FLE) represents the most important extratemporal type of focal epilepsy, characterization of A1 and A2A receptor binding is lacking. The aim of the present study was to characterize the A1 and A2A receptor binding in surgical tissue from patients with FLE.
Methods: Experiments were designed to determine A1 and A2A receptor binding in frontal cortex of surgically treated patients with FLE (n=21). Six patients had frontal lobe tumor, three had post-traumatic epilepsy and twelve had focal cortical dysplasia. In vitro autoradiography experiments were carried out using parallel brain section exposed to different experimental conditions: a) total binding: 5 nM [3H]CGS 21680 (30 Ci/mmol, an agonist of A1 and A2A receptors); b) A2A receptor binding: 5 nM [3H]CGS 21680 plus 100 nM of DPCPX (an antagonist of A1 receptors); c) non-specific binding: 5 nM [3H]CGS 21680 plus 100 nM of DPCPX plus 100 nM of SCH 58261 (an A2A antagonist). A1 receptor binding was estimated with the difference between total binding and A2A receptor binding. Cell count was evaluated in parallel sections processed with Nissl staining and unbiased stereology. Results obtained from patients with FLE were compared with those found in experiments using frontal cortex of autopsies (n=18).
Results: In contrast to the autopsy group, the neocortex of patients with FLE demonstrated lower cell count in the different cortical layers (layers I-II, 40.5%, p< 0.0001; layers III-IV, 36.7%, p< 0.0001; layers V-VI, 33.2%, p< 0.0001). Patients with FLE showed A2A binding values similar to those obtained from the autopsy group. This result was despite the cell loss found in cortex suggesting high A2A receptor binding. Concerning A1 receptors, the analysis revealed reduced binding in the neocortex of patients with FLE (layers I-II, 49.6%, p< 0.001; layers III-IV, 55 %, p< 0.0001; layers V-VI, 60.9%, p< 0.0001). These changes were maintained when the results were evaluated according to the etiology of the FLE.
Translational Research