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Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2

The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disea...

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Autores principales: Schoettner, Konrad, Alonso, Mariana, Button, Margo, Goldfarb, Cassandra, Herrera, Juliana, Quteishat, Nour, Meyer, Christiane, Bergdahl, Andreas, Amir, Shimon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216244/
https://www.ncbi.nlm.nih.gov/pubmed/35755440
http://dx.doi.org/10.3389/fphys.2022.922080
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author Schoettner, Konrad
Alonso, Mariana
Button, Margo
Goldfarb, Cassandra
Herrera, Juliana
Quteishat, Nour
Meyer, Christiane
Bergdahl, Andreas
Amir, Shimon
author_facet Schoettner, Konrad
Alonso, Mariana
Button, Margo
Goldfarb, Cassandra
Herrera, Juliana
Quteishat, Nour
Meyer, Christiane
Bergdahl, Andreas
Amir, Shimon
author_sort Schoettner, Konrad
collection PubMed
description The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of Bmal1 or Per2 from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of Gpr88. Whereas the conditional knockout of Bmal1 and Per2 had mild effects on affective behaviors, a pronounced effect on motor functions was found in Bmal1 knockout mice. Subsequent investigation revealed an attenuated response of Bmal1 knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of Bmal1 within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice.
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spelling pubmed-92162442022-06-23 Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2 Schoettner, Konrad Alonso, Mariana Button, Margo Goldfarb, Cassandra Herrera, Juliana Quteishat, Nour Meyer, Christiane Bergdahl, Andreas Amir, Shimon Front Physiol Physiology The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of Bmal1 or Per2 from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of Gpr88. Whereas the conditional knockout of Bmal1 and Per2 had mild effects on affective behaviors, a pronounced effect on motor functions was found in Bmal1 knockout mice. Subsequent investigation revealed an attenuated response of Bmal1 knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of Bmal1 within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice. Frontiers Media S.A. 2022-06-08 /pmc/articles/PMC9216244/ /pubmed/35755440 http://dx.doi.org/10.3389/fphys.2022.922080 Text en Copyright © 2022 Schoettner, Alonso, Button, Goldfarb, Herrera, Quteishat, Meyer, Bergdahl and Amir. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Schoettner, Konrad
Alonso, Mariana
Button, Margo
Goldfarb, Cassandra
Herrera, Juliana
Quteishat, Nour
Meyer, Christiane
Bergdahl, Andreas
Amir, Shimon
Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2
title Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2
title_full Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2
title_fullStr Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2
title_full_unstemmed Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2
title_short Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2
title_sort characterization of affective behaviors and motor functions in mice with a striatal-specific deletion of bmal1 and per2
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216244/
https://www.ncbi.nlm.nih.gov/pubmed/35755440
http://dx.doi.org/10.3389/fphys.2022.922080
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