Disruption of CREB function in brain leads to neurodegeneration
Abstract
Control of cellular survival and proliferation is dependent on extracellular signals and is a prerequisite for ordered tissue development and maintenance. Activation of the cAMP responsive element binding protein (CREB) by phosphorylation has been implicated in the survival of mammalian cells. To define its roles in the mouse central nervous system, we disrupted Creb1 in brain of developing and adult mice using the Cre/loxP system. Mice with a Crem(-/-) background and lacking Creb in the central nervous system during development show extensive apoptosis of postmitotic neurons. By contrast, mice in which both Creb1 and Crem are disrupted in the postnatal forebrain show progressive neurodegeneration in the hippocampus and in the dorsolateral striatum. The striatal phenotype is reminiscent of Huntington disease and is consistent with the postulated role of CREB-mediated signaling in polyglutamine-triggered diseases.
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Removing the creb1 gene in adult mouse forebrain or chronic inhibition of CREB function leads to extensive neurodegeneration in the hippocampus.
“Removing the creb1 gene in adult mouse forebrain or chronic inhibition of CREB function leads to extensive neurodegeneration in the hippocampus (67,68).”
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References 37 · Cited by 684
- Authors
- Mantamadiotis, T., Lemberger, T., Bleckmann, S. C., Kern, H., Kretz, O., Villalba, A. M., Tronche, F., Kellendonk, C., Gau, D., Kapfhammer, J., Otto, C., Schmid, W., & Schütz, G.
- Affiliations
- German Cancer Research Center (DE)
- University of Basel (CH)
- Corresponding author
- Schütz, Günther
- ORCID
- Venue
- Nature Genetics
- Published
- 2002-04-22
- Volume
- 31
- Issue
- 1
- Pages
- 47-54
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2030575711
- Cited by
- 684
- References
- 37
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 13 · 2023: 18 · 2022: 19 · 2021: 19 · 2020: 26 · 2019: 23 · 2018: 27 · 2017: 26 · 2016: 25 · 2015: 23 · 2014: 34 · 2013: 26 · 2012: 37
- FWCI
- 9.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- CREB, CREB1, CREM, neurodegeneration, neuronal apoptosis, postmitotic neurons, hippocampus, dorsolateral striatum, Huntington's disease, polyglutamine, brain development, knockout mice, transcriptional regulation
- MeSH terms
- Animals, Brain, Corpus Striatum, DNA-Binding Proteins, Female, Humans, Huntington Disease, Male, Mice, Transgenic, Nerve Degeneration, Peptides, Phenotype, Repressor Proteins, Transcription Factors, Signal Transduction, Apoptosis, Cyclic AMP Response Element-Binding Protein, Mice, Knockout, Mice, Cyclic AMP Response Element Modulator
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