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
Abstract
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.
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NPTXs could contribute to the long-term E/I imbalance characteristic of epilepsy by altering AMPAR neurotransmission.
“NPTXs could contribute to the long-term E/I imbalance characteristic of epilepsy by altering AMPAR neurotransmission (Bonansco and Fuenzalida 2016; Lopes et al. 2013).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Lopes et al. 2013
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- Authors
- Lopes, M. W., Soares, F. M. S., de Mello, N., Nunes, J. C., Cajado, A. G., de Brito, D., de Cordova, F. M., da Cunha, R. M. S., Walz, R., & Leal, R. B.
- Affiliations
- Universidade Federal de Santa Catarina (BR)
- State University of Vale do Acaraú (BR)
- Corresponding author
- Leal, Rodrigo Bainy
- ORCID
- Venue
- Experimental Brain Research
- Published
- 2013-02-08
- Volume
- 226
- Issue
- 2
- Pages
- 153-163
- ISSN
- 0014-4819 (ISSN-L)
- 1432-1106
- OpenAlex
- W2043247184
- Cited by
- 78
- References
- 50
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 8 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 11 · 2015: 8 · 2014: 9 · 2013: 1
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Experimental Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- pilocarpine-induced status epilepticus, mesial temporal lobe epilepsy, hippocampal sclerosis, NMDA receptor 1, glial glutamate transporters, GLAST, GLT-1, glutamatergic neurotransmission, epileptogenesis, hippocampus, cerebral cortex, time-dependent changes
- MeSH terms
- Animals, Cerebral Cortex, Disease Models, Animal, Epilepsy, Temporal Lobe, Gene Expression Regulation, Hippocampus, Male, Neuroglia, Phosphorylation, Pilocarpine, RNA, Messenger, Time Factors, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Receptors, AMPA, Excitatory Amino Acid Transporter 1, Excitatory Amino Acid Transporter 2, Rats
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