CRE-mediated transcription and COX-2 expression in the pilocarpine model of status epilepticus
Open accessAbstract
Status epilepticus (SE) triggers neuronal death, reactive gliosis and remodeling of synaptic circuitry, thus leading to profound pathological alterations in CNS physiology. These processes are, in part, regulated by the rapid upregulation of both cytotoxic and cytoprotective genes. One pathway that may couple SE to transcriptionally dependent alterations in CNS physiology is the CREB (cAMP response element-binding protein)/CRE (cAMP response element) cascade. Here, we utilized the pilocarpine model of SE on a mouse strain transgenic for a CRE-reporter construct (beta-galactosidase) to begin to characterize how seizure activity regulates the activation state of the CREB/CRE pathway in both glia and neurons of the hippocampus. SE triggered a rapid (4-8 h post-SE) but transient increase in CRE-mediated gene expression in the neuronal sublayers. In contrast to neurons, SE induced a lasting increase (up to 20 days) in CRE-mediated transcription in both reactive astrocytes and microglia. CRE-mediated gene expression correlated with expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2). To examine the role of CREB in SE-induced COX-2 expression, we generated a transgenic mouse strain that expresses A-CREB, a potent repressor of CREB-dependent transcription. In these animals, the capacity of SE to stimulate COX-2 expression was markedly attenuated, indicating that CREB is a key intermediate in SE-induced COX-2 expression. Collectively these data show that SE triggers two waves of CREB-mediated gene expression, a transient wave in neurons and a long-lasting wave in reactive glial cells, and that CREB couples SE to COX-2 expression.
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Seizures are associated with increased expression of several neurotrophic-related genes, including transcription factors, neuropeptides, and growth factors.
“Seizures have been associated with an increased expression of several neurotrophic-related genes, including transcription factors [176], neuropeptides [177], and growth factors [178].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [176]
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- Authors
- Lee, B., Dziema, H., Lee, K. H., Choi, Y.-S., & Obrietan, K.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Obrietan, Karl
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 25
- Issue
- 1
- Pages
- 80-91
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC1900429
- OpenAlex
- W2054401541
- Cited by
- 71
- References
- 84
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 4 · 2016: 3 · 2015: 6 · 2014: 2 · 2013: 2 · 2012: 6
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Heart Association
- Epilepsy Foundation
- Ohio State University
- National Institutes of Health
- National Institute of Mental Health (R01MH062335)
- National Institute of Neurological Disorders and Stroke (R01NS047176, P30NS045758, NS47176)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- status epilepticus, CREB, cyclooxygenase-2, pilocarpine model, reactive astrocytes, microglia, hippocampus, glial gene expression, neuronal cell death, neuroinflammation
- MeSH terms
- Animals, Astrocytes, Cell Line, Data Interpretation, Statistical, Fluoresceins, Fluorescent Antibody Technique, Fluorescent Dyes, Immunohistochemistry, Male, Mice, Inbred C57BL, Mice, Transgenic, Organic Chemicals, Pilocarpine, Status Epilepticus, Transcription, Genetic, Blotting, Western, Signal Transduction, Gene Expression Regulation, Enzymologic, Cyclic AMP Response Element-Binding Protein, Microglia, Genes, Reporter, Muscarinic Agonists, Mice, Cyclooxygenase 2
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