GIRARDI Elena Silvia
3-MERCAPTOPROPIONIC ACID - INDUCED REPETITIVE SEIZURES INCREASE GluN2A EXPRESSION IN RAT HIPPOCAMPUS. A POTENTIAL NEUROPROTECTIVE ROLE OF CYCLOPENTYLADENOSINE
GORI MB, GIRARDI E
CELLULAR AND MOLECULAR NEUROBIOLOGY.
Lugar: New York (En revisión); Año: 2013
Abstract The N-methyl-D-aspartate receptor (NMDAR) is involved in synaptic plasticity, learning, memory and neurological diseases like epilepsy and it is the major mediator of excitotoxicity. Functional NMDARs in the mature brain are heteromeric complexes composed of different subunits: GluN1 and GluN2. There are four different GluN2 subunits (A-D) and each of them critically determines the pharmacological and electrophysiological properties of NMDARs. GluN1 is ubiquitously expressed in the central nervous system while the highest GluN2A expression is in hippocampus. Adenosine, an endogenous anticonvulsant, is a neuromodulator with a critical role in the regulation of neuronal activity, mediating its effect on specific receptors, among which Adenosine A1 receptor is highly expressed in hippocampus. In the present work hippocampal GluN2A expression after the convulsant drug 3-mercaptopropionic acid (MP) -induced seizures and the effect of cyclopentyladenosine (CPA) given alone or prior to MP (CPA+MP) in an acute or repetitive experimental model was studied. CPA administered to rats for one or four days, increases seizure threshold induced by MP. After one administration of MP, CPA and CPA+MP no significant difference in GluN2A expression was observed by western blot, although immunohistochemistry revealed an increase in CA2/3 area. However, repetitive MP administration during four days showed a significant increase of GluN2A expression, and the repetitive administration of CPA 30 minutes prior to MP caused a significant decrease of GluN2A expression with respect to MP treatment, returning to control levels. These results show that GluN2A subunit is involved in repetitive MP-induced seizures, while CPA administration displays a protective effect against it.