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Pumilio-2 Function in the Mouse Nervous System

Coordinated mRNA translation at the synapse is increasingly recognized as a critical mechanism for neuronal regulation. Pumilio, a translational regulator, is known to be involved in neuronal homeostasis and memory formation in Drosophila. Most recently, the mammalian Pumilio homolog Pumilio-2 (Pum2...

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Autores principales: Siemen, Henrike, Colas, Damien, Heller, H. Craig, Brüstle, Oliver, Reijo Pera, Renee A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189250/
https://www.ncbi.nlm.nih.gov/pubmed/22016787
http://dx.doi.org/10.1371/journal.pone.0025932
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author Siemen, Henrike
Colas, Damien
Heller, H. Craig
Brüstle, Oliver
Reijo Pera, Renee A.
author_facet Siemen, Henrike
Colas, Damien
Heller, H. Craig
Brüstle, Oliver
Reijo Pera, Renee A.
author_sort Siemen, Henrike
collection PubMed
description Coordinated mRNA translation at the synapse is increasingly recognized as a critical mechanism for neuronal regulation. Pumilio, a translational regulator, is known to be involved in neuronal homeostasis and memory formation in Drosophila. Most recently, the mammalian Pumilio homolog Pumilio-2 (Pum2) has been found to play a role in the mammalian nervous system, in particular in regulating morphology, arborization and excitability of neuronal dendrites, in vitro. However, the role of Pum2 in vivo remains unclear. Here, we report our investigation of the functional and molecular consequences of Pum2 disruption in vivo using an array of neurophysiology, behavioral and gene expression profiling techniques. We used Pum2-deficient mice to monitor in vivo brain activity using EEG and to study behavior traits, including memory, locomotor activity and nesting capacities. Because of the suspected role of Pum2 in neuronal excitability, we also examined the susceptibility to seizure induction. Finally, we used a quantitative gene expression profiling assay to identify key molecular partners of Pum2. We found that Pum2-deficient mice have abnormal behavioral strategies in spatial and object memory test. Additionally, Pum2 deficiency is associated with increased locomotor activity and decreased body weight. We also observed environmentally-induced impairment in nesting behavior. Most importantly, Pum2-deficient mice showed spontaneous EEG abnormalities and had lower seizure thresholds using a convulsing dosage of pentylenetetrazole. Finally, some genes, including neuronal ion channels, were differentially expressed in the hippocampus of Pum2-deficient mice. These findings demonstrate that Pum2 serves key functions in the adult mammalian central nervous system encompassing neuronal excitability and behavioral response to environmental challenges.
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spelling pubmed-31892502011-10-20 Pumilio-2 Function in the Mouse Nervous System Siemen, Henrike Colas, Damien Heller, H. Craig Brüstle, Oliver Reijo Pera, Renee A. PLoS One Research Article Coordinated mRNA translation at the synapse is increasingly recognized as a critical mechanism for neuronal regulation. Pumilio, a translational regulator, is known to be involved in neuronal homeostasis and memory formation in Drosophila. Most recently, the mammalian Pumilio homolog Pumilio-2 (Pum2) has been found to play a role in the mammalian nervous system, in particular in regulating morphology, arborization and excitability of neuronal dendrites, in vitro. However, the role of Pum2 in vivo remains unclear. Here, we report our investigation of the functional and molecular consequences of Pum2 disruption in vivo using an array of neurophysiology, behavioral and gene expression profiling techniques. We used Pum2-deficient mice to monitor in vivo brain activity using EEG and to study behavior traits, including memory, locomotor activity and nesting capacities. Because of the suspected role of Pum2 in neuronal excitability, we also examined the susceptibility to seizure induction. Finally, we used a quantitative gene expression profiling assay to identify key molecular partners of Pum2. We found that Pum2-deficient mice have abnormal behavioral strategies in spatial and object memory test. Additionally, Pum2 deficiency is associated with increased locomotor activity and decreased body weight. We also observed environmentally-induced impairment in nesting behavior. Most importantly, Pum2-deficient mice showed spontaneous EEG abnormalities and had lower seizure thresholds using a convulsing dosage of pentylenetetrazole. Finally, some genes, including neuronal ion channels, were differentially expressed in the hippocampus of Pum2-deficient mice. These findings demonstrate that Pum2 serves key functions in the adult mammalian central nervous system encompassing neuronal excitability and behavioral response to environmental challenges. Public Library of Science 2011-10-07 /pmc/articles/PMC3189250/ /pubmed/22016787 http://dx.doi.org/10.1371/journal.pone.0025932 Text en Siemen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Siemen, Henrike
Colas, Damien
Heller, H. Craig
Brüstle, Oliver
Reijo Pera, Renee A.
Pumilio-2 Function in the Mouse Nervous System
title Pumilio-2 Function in the Mouse Nervous System
title_full Pumilio-2 Function in the Mouse Nervous System
title_fullStr Pumilio-2 Function in the Mouse Nervous System
title_full_unstemmed Pumilio-2 Function in the Mouse Nervous System
title_short Pumilio-2 Function in the Mouse Nervous System
title_sort pumilio-2 function in the mouse nervous system
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189250/
https://www.ncbi.nlm.nih.gov/pubmed/22016787
http://dx.doi.org/10.1371/journal.pone.0025932
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