Anticonvulsant effect of reduced NMDA receptor expression in audiogenic DBA/2 mice
Abstract
Pretreatment of DBA/2 mice (n = 14-15 per group) with an 18-mer antisense probe to the NMDA-receptor submit NR1 (2 x 1 micrograms, or 2 x 83 pmol, NR1 antisense probe intracerebroventricularly, -29 and -7 h before testing for seizure response) resulted in almost complete suppression of sound-induced clonic seizures. A saline-treated group gave a 100% seizures response, while the group treated with NR1 antisense probe gave a 7% seizure response to the sound stimulus. The group treated with NR1 nonsense-probe showed no anticonvulsant protection (93% seizure response). The anticonvulsant protection observed following NR1 antisense administration was of relatively short duration, with seizure response gradually returning to control levels 12 to 24 h following the termination of antisense administration. When NR1 receptor levels were assessed by receptor autoradiography ([3H]-MK 801 and -CGP 39653 binding) in the same groups of mice, significant (20%) reductions in NR1 levels were observed in the retrosplenial cortex and the overall cortex. The seizure-induced expression of c-fos and NGFI-A in thalamus, hypothalamus, inferior colliculus and medical geniculate seen in vehicle- and NR1 nonsense-treated mice was completely blocked by NR1 antisense pretreatment.
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Rbfox1−/− splicing changes affect transcripts encoding ion channels, neurotransmitter receptors, structural proteins and Ca2+ signalling molecules.
“However, these splicing changes affect transcripts encoding ion channels, neurotransmitter receptors, structural proteins and Ca2+ signalling molecules”
From The neurogenetics of alternative splicing (2016) · cites this paper as [134]
Many of the transcripts affected by Rbfox1−/− splicing changes are associated with seizure disorders in humans or mice.
“many of which are associated with seizure disorders in humans or mice, such as the GABAA receptor subunit Gabrg2, Grin1, the voltage-gated sodium channel Scn8a (which encodes NaV1.6), and synaptosomal-associated protein 25 (Snap25)133–137”
From The neurogenetics of alternative splicing (2016) · cites this paper as [134]
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The neurogenetics of alternative splicing
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The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain
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- Authors
- Chapman, A. G., Woodburn, V. L., Woodruff, G. N., & Meldrum, B. S.
- Affiliations
- Addenbrooke's Hospital (GB)
- Corresponding author
- Chapman, A.G.
- Venue
- Epilepsy Research
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 26
- Issue
- 1
- Pages
- 25-35
- ISSN
- 0920-1211 (ISSN-L)
- OpenAlex
- W2075772453
- Cited by
- 26
- References
- 54
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2016: 1 · 2015: 2 · 2013: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epilepsy 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
- NMDA receptor, NR1 subunit, antisense oligonucleotides, audiogenic seizures, DBA/2 mice, anticonvulsant activity, clonic seizures, c-fos, NGFI-A, retrosplenial cortex, thalamus, inferior colliculus, medial geniculate body, MK-801 binding
- MeSH terms
- Acoustic Stimulation, Animals, Autoradiography, Cerebral Cortex, Female, Inferior Colliculi, Male, Mice, Inbred DBA, RNA, Messenger, Seizures, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Antisense Elements (Genetics), Genes, Immediate-Early, Codon, Nonsense, Mice
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