Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

• Published in: Experimental brain research 2013-04, Vol.226 (2), p.153-163
• Main Authors: Lopes, Mark William, Soares, Flávia Mahatma Schneider, de Mello, Nelson, Nunes, Jean Costa, Cajado, Aurilene Gomes, de Brito, Daniel, de Cordova, Fabiano Mendes, da Cunha, Rodrigo Maranguape Silva, Walz, Roger, Leal, Rodrigo Bainy
• Format: Article
• Language: English
• Subjects: AMPA receptors; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Care and treatment; Cerebral cortex; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Convulsions & seizures; Diagnosis; Disease Models, Animal; Epilepsy; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - genetics; Epilepsy, Temporal Lobe - metabolism; Excitatory Amino Acid Transporter 1 - biosynthesis; Excitatory Amino Acid Transporter 1 - genetics; Excitatory Amino Acid Transporter 2 - biosynthesis; Excitatory Amino Acid Transporter 2 - genetics; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - drug effects; Hippocampus - metabolism; Kinases; Male; Medical sciences; Nervous system (semeiology, syndromes); Neuroglia - metabolism; Neurology; Neurosciences; Phosphorylation; Phosphorylation - drug effects; Phosphorylation - physiology; Physiological aspects; Pilocarpine - toxicity; Proteins; Rats; Rats, Wistar; Receptors, AMPA - biosynthesis; Receptors, AMPA - genetics; Receptors, N-Methyl-D-Aspartate - biosynthesis; Receptors, N-Methyl-D-Aspartate - genetics; Research Article; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal transduction; Time Factors; Vertebrates: nervous system and sense organs
• ISSN: 0014-4819; 1432-1106
• DOI: 10.1007/s00221-013-3421-8

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N -methyl- d -aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser 845 in the Ctx and GluR1-Ser 831 in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.