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Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development

Endocannabinoid (eCB) signaling system (ECS), encompassing cannabinoid receptors and enzymes involved in the synthesis and degradation of the endogenous cannabinoid signaling lipids, is highly expressed in the cerebellar cortex of adult humans and rodents. In addition to their well-established role...

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Autores principales: Martinez, Luis Ricardo, Black, Kylie Caroline, Webb, Brynna Tellas, Bell, Alexandria, Baygani, Shawyon Kevin, Mier, Tristen Jay, Dominguez, Luis, Mackie, Ken, Kalinovsky, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189485/
https://www.ncbi.nlm.nih.gov/pubmed/32179579
http://dx.doi.org/10.1523/ENEURO.0471-19.2020
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author Martinez, Luis Ricardo
Black, Kylie Caroline
Webb, Brynna Tellas
Bell, Alexandria
Baygani, Shawyon Kevin
Mier, Tristen Jay
Dominguez, Luis
Mackie, Ken
Kalinovsky, Anna
author_facet Martinez, Luis Ricardo
Black, Kylie Caroline
Webb, Brynna Tellas
Bell, Alexandria
Baygani, Shawyon Kevin
Mier, Tristen Jay
Dominguez, Luis
Mackie, Ken
Kalinovsky, Anna
author_sort Martinez, Luis Ricardo
collection PubMed
description Endocannabinoid (eCB) signaling system (ECS), encompassing cannabinoid receptors and enzymes involved in the synthesis and degradation of the endogenous cannabinoid signaling lipids, is highly expressed in the cerebellar cortex of adult humans and rodents. In addition to their well-established role in neuromodulation, eCBs have been shown to play key roles in aspects of neurodevelopment in the fore- and mid-brain, including neurogenesis, cell migration, and synapse specification. However, little is known about the role of ECS in cerebellar development. In this study, we conducted immunohistochemical characterization of ECS components through key stages of cerebellar development in mice using antibodies for 2-arachidonoylglycerol (2-AG) synthetizing and degrading enzymes and the major brain cannabinoid receptor, cannabinoid receptor 1 (CB1), in combination with cerebellar cell markers. Our results reveal a temporally, spatially, and cytologically dynamic pattern of expression. Production, receptor binding, and degradation of eCBs are tightly controlled, thus localization of eCB receptors and the complementary cannabinoid signaling machinery determines the direction, duration, and ultimately the outcome of eCB signaling. To gain insights into the role of eCB signaling in cerebellar development, we characterized gross anatomy of cerebellar midvermis in CB1 knock-out (CB1 KO) mice, as well as their performance in cerebellar-influenced motor tasks. Our results show persistent and selective anatomic and behavioral alterations in CB1 KOs. Consequently, the insights gained from this study lay down the foundation for investigating specific cellular and molecular mechanisms regulated by eCB signaling during cerebellar development.
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spelling pubmed-71894852020-04-29 Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development Martinez, Luis Ricardo Black, Kylie Caroline Webb, Brynna Tellas Bell, Alexandria Baygani, Shawyon Kevin Mier, Tristen Jay Dominguez, Luis Mackie, Ken Kalinovsky, Anna eNeuro Research Article: New Research Endocannabinoid (eCB) signaling system (ECS), encompassing cannabinoid receptors and enzymes involved in the synthesis and degradation of the endogenous cannabinoid signaling lipids, is highly expressed in the cerebellar cortex of adult humans and rodents. In addition to their well-established role in neuromodulation, eCBs have been shown to play key roles in aspects of neurodevelopment in the fore- and mid-brain, including neurogenesis, cell migration, and synapse specification. However, little is known about the role of ECS in cerebellar development. In this study, we conducted immunohistochemical characterization of ECS components through key stages of cerebellar development in mice using antibodies for 2-arachidonoylglycerol (2-AG) synthetizing and degrading enzymes and the major brain cannabinoid receptor, cannabinoid receptor 1 (CB1), in combination with cerebellar cell markers. Our results reveal a temporally, spatially, and cytologically dynamic pattern of expression. Production, receptor binding, and degradation of eCBs are tightly controlled, thus localization of eCB receptors and the complementary cannabinoid signaling machinery determines the direction, duration, and ultimately the outcome of eCB signaling. To gain insights into the role of eCB signaling in cerebellar development, we characterized gross anatomy of cerebellar midvermis in CB1 knock-out (CB1 KO) mice, as well as their performance in cerebellar-influenced motor tasks. Our results show persistent and selective anatomic and behavioral alterations in CB1 KOs. Consequently, the insights gained from this study lay down the foundation for investigating specific cellular and molecular mechanisms regulated by eCB signaling during cerebellar development. Society for Neuroscience 2020-04-21 /pmc/articles/PMC7189485/ /pubmed/32179579 http://dx.doi.org/10.1523/ENEURO.0471-19.2020 Text en Copyright © 2020 Martinez et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: New Research
Martinez, Luis Ricardo
Black, Kylie Caroline
Webb, Brynna Tellas
Bell, Alexandria
Baygani, Shawyon Kevin
Mier, Tristen Jay
Dominguez, Luis
Mackie, Ken
Kalinovsky, Anna
Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development
title Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development
title_full Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development
title_fullStr Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development
title_full_unstemmed Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development
title_short Components of Endocannabinoid Signaling System Are Expressed in the Perinatal Mouse Cerebellum and Required for Its Normal Development
title_sort components of endocannabinoid signaling system are expressed in the perinatal mouse cerebellum and required for its normal development
topic Research Article: New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189485/
https://www.ncbi.nlm.nih.gov/pubmed/32179579
http://dx.doi.org/10.1523/ENEURO.0471-19.2020
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