GIRARDI Elena Silvia
congresos y reuniones científicas
Experimental Epilepsy:Study of NMDAreceptor NR2A subunit and PSD-95 expression. Effect of Cyclopentyladenosine
GIRARDI E, GORI MB
Congreso; 23th biennial meeting ISN-ESN.; 2011
International Society for Neurochemistry and European Society for Neurochemistry
N-methyl-D-aspartate receptors (NMDARs) play key roles in excitatory synaptic transmission and have been implicated in neurological disorders. NMDARs are heteromeric complexes and and most of the NMDARs function as tetramer assemblies requires the subunit NR1 (essential) and two NR2 subunits of the four isoforms: NR2A-NR2D. The complex of proteins NR1/NR2A interacts with many of the synapse-associated proteins, including the protein postsynaptic density 95 (PSD-95). This interaction can be altered in CNS epilepsy. The objective of this work is to study the effect of the administration of the convulsant drug 3-mercaptopropionic acid (MP), during one or four days, and the adenosine analogue cyclopentyladenosine (CPA) on NR2A and PSD-95 expression. Methods: Wistar rats (250-300g) were daily injected with MP 45mg/kg i.p., or CPA (2mg/kg) or CPA 30 minutes previous MP (CPA + MP) during 1 or 4 days. Control rats were injected with saline. Western blot assays on the whole hippocampal tissue showed no change after an unique doses of MP in NR2A and PSd-95, while a significant increase in NR2A and PSD-95 expression (47-53%) with respect to control after 4 days of MP administration. CPA previuos MP recovered the normal values and a tendency to reduce NR2A and PSD-95 expression after CPA administration was observed. Immunoassays of NR2A and PSD-95 showed hippocampal pyramidal layer staining. These results show that repetitive MP-induced seizures increase NR2A and PSD-95 expression,but no a single administration, suggesting an excitotoxic effect sfter repetitivt doses, while the administration of the adenosine analogue CPA has a protective effect.