NeuroMolecular Medicine

, Volume 15, Issue 2, pp 324–338

AMPA Receptor Properties are Modulated in the Early Stages Following Pilocarpine-induced Status Epilepticus

Authors

  • Isabella Russo
    • Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology and National Institute of NeuroscienceUniversity of Brescia
  • Daniela Bonini
    • Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology and National Institute of NeuroscienceUniversity of Brescia
  • Luca La Via
    • Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology and National Institute of NeuroscienceUniversity of Brescia
  • Sergio Barlati
    • Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology and National Institute of NeuroscienceUniversity of Brescia
    • Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology and National Institute of NeuroscienceUniversity of Brescia
Original Paper

DOI: 10.1007/s12017-013-8221-6

Cite this article as:
Russo, I., Bonini, D., Via, L.L. et al. Neuromol Med (2013) 15: 324. doi:10.1007/s12017-013-8221-6

Abstract

Glutamate over-activation and the consequent neuronal excitotoxicity have been identified as crucial players in brain dysfunctions such as status epilepticus (SE). Owing to the central function of 2-amino-3-(hydroxyl-5-methylisoxazole-4-yl) propionic acid receptors (AMPARs) in fast excitatory neurotransmission, these receptors have been recognized to play a prominent role in the development and generation of epileptic seizure. This study was undertaken to investigate both the early changes that affect glutamatergic neurons in the rat cerebral cortex and hippocampus and the level and channel properties of AMPARs in response to SE. The results obtained after 3 h of pilocarpine (PILO)-induced SE showed a disorganization of glutamatergic neurons in the CA3 and a thinner neuronal cell layer in the dentate gyrus (DG) region as compared with controls. A significant increase in AMPAR GluA2 protein expression, a decrease in GluA1, GluA3, and GluA4 expression, and a reduction in the phosphorylation of Ser831-GluA1 and Ser880-GluA2 were also observed. In addition, we report a downregulation of R/G editing levels and of Flip splicing isoforms, with a prominent effect on the hippocampus of PILO-treated rats. Our results suggest the presence of an attenuation of AMPARs’ post-synaptic excitatory response to glutamate after PILO treatment, thus conferring neuronal protection from the excitotoxic conditions observed in the SE. This study suggests a role for AMPARs in alterations of the glutamatergic pathway during the onset and early progression of epilepsy, thus indicating additional targets for potential therapeutic interventions.

Keywords

AMPA receptors RNA editing RNA splicing Pilocarpine Status epilepticus Excitotoxicity

Supplementary material

12017_2013_8221_MOESM1_ESM.doc (373 kb)
Supplementary material 1 (DOC 373 kb)

Copyright information

© Springer Science+Business Media New York 2013