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Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse

Pathological repetitive behaviours are a common feature of various neuropsychiatric disorders, including compulsions in obsessive–compulsive disorder or tics in Gilles de la Tourette syndrome. Clinical research suggests that compulsive-like symptoms are related to associative cortico-striatal dysfun...

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Autores principales: Lousada, Eliana, Boudreau, Mathieu, Cohen-Adad, Julien, Nait Oumesmar, Brahim, Burguière, Eric, Schreiweis, Christiane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570333/
https://www.ncbi.nlm.nih.gov/pubmed/34679417
http://dx.doi.org/10.3390/brainsci11101353
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author Lousada, Eliana
Boudreau, Mathieu
Cohen-Adad, Julien
Nait Oumesmar, Brahim
Burguière, Eric
Schreiweis, Christiane
author_facet Lousada, Eliana
Boudreau, Mathieu
Cohen-Adad, Julien
Nait Oumesmar, Brahim
Burguière, Eric
Schreiweis, Christiane
author_sort Lousada, Eliana
collection PubMed
description Pathological repetitive behaviours are a common feature of various neuropsychiatric disorders, including compulsions in obsessive–compulsive disorder or tics in Gilles de la Tourette syndrome. Clinical research suggests that compulsive-like symptoms are related to associative cortico-striatal dysfunctions, and tic-like symptoms to sensorimotor cortico-striatal dysfunctions. The Sapap3 knockout mouse (Sapap3-KO), the current reference model to study such repetitive behaviours, presents both associative as well as sensorimotor cortico-striatal dysfunctions. Previous findings point to deficits in both macro-, as well as micro-circuitry, both of which can be affected by neuronal structural changes. However, to date, structural connectivity has not been analysed. Hence, in the present study, we conducted a comprehensive structural characterisation of both associative and sensorimotor striatum as well as major cortical areas connecting onto these regions. Besides a thorough immunofluorescence study on oligodendrocytes, we applied AxonDeepSeg, an open source software, to automatically segment and characterise myelin thickness and axon area. We found that axon calibre, the main contributor to changes in conduction speed, is specifically reduced in the associative striatum of the Sapap3-KO mouse; myelination per se seems unaffected in associative and sensorimotor cortico-striatal circuits.
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spelling pubmed-85703332021-11-06 Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse Lousada, Eliana Boudreau, Mathieu Cohen-Adad, Julien Nait Oumesmar, Brahim Burguière, Eric Schreiweis, Christiane Brain Sci Article Pathological repetitive behaviours are a common feature of various neuropsychiatric disorders, including compulsions in obsessive–compulsive disorder or tics in Gilles de la Tourette syndrome. Clinical research suggests that compulsive-like symptoms are related to associative cortico-striatal dysfunctions, and tic-like symptoms to sensorimotor cortico-striatal dysfunctions. The Sapap3 knockout mouse (Sapap3-KO), the current reference model to study such repetitive behaviours, presents both associative as well as sensorimotor cortico-striatal dysfunctions. Previous findings point to deficits in both macro-, as well as micro-circuitry, both of which can be affected by neuronal structural changes. However, to date, structural connectivity has not been analysed. Hence, in the present study, we conducted a comprehensive structural characterisation of both associative and sensorimotor striatum as well as major cortical areas connecting onto these regions. Besides a thorough immunofluorescence study on oligodendrocytes, we applied AxonDeepSeg, an open source software, to automatically segment and characterise myelin thickness and axon area. We found that axon calibre, the main contributor to changes in conduction speed, is specifically reduced in the associative striatum of the Sapap3-KO mouse; myelination per se seems unaffected in associative and sensorimotor cortico-striatal circuits. MDPI 2021-10-14 /pmc/articles/PMC8570333/ /pubmed/34679417 http://dx.doi.org/10.3390/brainsci11101353 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lousada, Eliana
Boudreau, Mathieu
Cohen-Adad, Julien
Nait Oumesmar, Brahim
Burguière, Eric
Schreiweis, Christiane
Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse
title Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse
title_full Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse
title_fullStr Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse
title_full_unstemmed Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse
title_short Reduced Axon Calibre in the Associative Striatum of the Sapap3 Knockout Mouse
title_sort reduced axon calibre in the associative striatum of the sapap3 knockout mouse
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570333/
https://www.ncbi.nlm.nih.gov/pubmed/34679417
http://dx.doi.org/10.3390/brainsci11101353
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