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Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus

Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic sign...

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Autores principales: Zimmermann, Tina, Maroso, Mattia, Beer, Annika, Baddenhausen, Sarah, Ludewig, Susann, Fan, Wenqiang, Vennin, Constance, Loch, Sebastian, Berninger, Benedikt, Hofmann, Clementine, Korte, Martin, Soltesz, Ivan, Lutz, Beat, Leschik, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215469/
https://www.ncbi.nlm.nih.gov/pubmed/30307491
http://dx.doi.org/10.1093/cercor/bhy258
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author Zimmermann, Tina
Maroso, Mattia
Beer, Annika
Baddenhausen, Sarah
Ludewig, Susann
Fan, Wenqiang
Vennin, Constance
Loch, Sebastian
Berninger, Benedikt
Hofmann, Clementine
Korte, Martin
Soltesz, Ivan
Lutz, Beat
Leschik, Julia
author_facet Zimmermann, Tina
Maroso, Mattia
Beer, Annika
Baddenhausen, Sarah
Ludewig, Susann
Fan, Wenqiang
Vennin, Constance
Loch, Sebastian
Berninger, Benedikt
Hofmann, Clementine
Korte, Martin
Soltesz, Ivan
Lutz, Beat
Leschik, Julia
author_sort Zimmermann, Tina
collection PubMed
description Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive. NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1). To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice. Here, we show that lack of CB1 in NSCs is sufficient to decrease proliferation of the stem cell pool, which consequently leads to a reduction in the number of newborn neurons. Furthermore, neuronal differentiation was compromised at the level of dendritic maturation pointing towards a postsynaptic role of CB1 in vivo. Deteriorated neurogenesis in NSC-specific CB1 knock-outs additionally resulted in reduced long-term potentiation in the hippocampal formation. The observed cellular and physiological alterations led to decreased short-term spatial memory and increased depression-like behavior. These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior.
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spelling pubmed-62154692018-11-06 Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus Zimmermann, Tina Maroso, Mattia Beer, Annika Baddenhausen, Sarah Ludewig, Susann Fan, Wenqiang Vennin, Constance Loch, Sebastian Berninger, Benedikt Hofmann, Clementine Korte, Martin Soltesz, Ivan Lutz, Beat Leschik, Julia Cereb Cortex Original Articles Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive. NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1). To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice. Here, we show that lack of CB1 in NSCs is sufficient to decrease proliferation of the stem cell pool, which consequently leads to a reduction in the number of newborn neurons. Furthermore, neuronal differentiation was compromised at the level of dendritic maturation pointing towards a postsynaptic role of CB1 in vivo. Deteriorated neurogenesis in NSC-specific CB1 knock-outs additionally resulted in reduced long-term potentiation in the hippocampal formation. The observed cellular and physiological alterations led to decreased short-term spatial memory and increased depression-like behavior. These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior. Oxford University Press 2018-12 2018-10-11 /pmc/articles/PMC6215469/ /pubmed/30307491 http://dx.doi.org/10.1093/cercor/bhy258 Text en © The Author(s) 2018. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Zimmermann, Tina
Maroso, Mattia
Beer, Annika
Baddenhausen, Sarah
Ludewig, Susann
Fan, Wenqiang
Vennin, Constance
Loch, Sebastian
Berninger, Benedikt
Hofmann, Clementine
Korte, Martin
Soltesz, Ivan
Lutz, Beat
Leschik, Julia
Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus
title Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus
title_full Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus
title_fullStr Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus
title_full_unstemmed Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus
title_short Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus
title_sort neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215469/
https://www.ncbi.nlm.nih.gov/pubmed/30307491
http://dx.doi.org/10.1093/cercor/bhy258
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