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The Endocannabinoid Anandamide Inhibits Neuronal Progenitor Cell Differentiation through Attenuation of the Rap1/B-Raf/ERK Pathway
Open accessAbstract
Endocannabinoids are neuromodulators that act as retrograde synaptic messengers inhibiting the release of different neurotransmitters in cerebral areas such as hippocampus, cortex, and striatum. However, little is known about other roles of the endocannabinoid system in brain. In the present work we provide substantial evidence that the endocannabinoid anandamide (AEA) regulates neuronal differentiation both in culture and in vivo. Thus AEA, through the CB(1) receptor, inhibited cortical neuron progenitor differentiation to mature neuronal phenotype. In addition, human neural stem cell differentiation and nerve growth factor-induced PC12 cell differentiation were also inhibited by cannabinoid challenge. AEA decreased PC12 neuronal-like generation via CB(1)-mediated inhibition of sustained extracellular signal-regulated kinase (ERK) activation, which is responsible for nerve growth factor action. AEA thus inhibited TrkA-induced Rap1/B-Raf/ERK activation. Finally, immunohistochemical analyses by confocal microscopy revealed that adult neurogenesis in dentate gyrus was significantly decreased by the AEA analogue methanandamide and increased by the CB(1) antagonist SR141716. These data indicate that endocannabinoids inhibit neuronal progenitor cell differentiation through attenuation of the ERK pathway and suggest that they constitute a new physiological system involved in the regulation of neurogenesis.
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Cites
Molecular characterization of a peripheral receptor for cannabinoids
Munro, S., Thomas, K. L., & Abu-Shaar, M. (1993) · Nature · doi:10.1038/365061a0 · Cited by 5,092
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Functional neurogenesis in the adult hippocampus
van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., & Gage, F. H. (2002) · Nature · doi:10.1038/4151030a · Cited by 2,853
Cited by
Adult neurogenesis and functional plasticity in neuronal circuits
Lledo, P.-M., Alonso, M., & Grubb, M. S. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1867 · Cited by 1,366
Adult neurogenesis: from precursors to network and physiology
Abrous, D. N., Koehl, M., & Le Moal, M. (2005) · Physiological Reviews · doi:10.1152/physrev.00055.2003 · Cited by 971
Genomic Analysis of Mouse Retinal Development
Blackshaw, S., Harpavat, S., Trimarchi, J., Cai, L., Huang, H., Kuo, W. P., Weber, G., Lee, K., Fraioli, R. E., Cho, S.-H., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020247 · Cited by 585
Jiang, W. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25509 · Cited by 527
Cannabinoid Receptor Signaling
Howlett, A. C. (2005) · Handbook of Experimental Pharmacology · doi:10.1007/3-540-26573-2_2 · Cited by 446
Metadata
- Authors
- Rueda, D., Navarro, B., Martı́nez-Serrano, A., Guzmán, M., & Galve-Roperh, I.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 277
- Issue
- 48
- Pages
- 46645-46650
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1984145099
- Cited by
- 254
- References
- 4
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rueda, D., Navarro, B., Martı́nez-Serrano, A., Guzmán, M., & Galve-Roperh, I. (2002). The Endocannabinoid Anandamide Inhibits Neuronal Progenitor Cell Differentiation through Attenuation of the Rap1/B-Raf/ERK Pathway. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m206590200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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