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Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders

Autism spectrum disorders (ASD) are neurodevelopmental diseases characterised by deficits in social communication, restricted interests, and repetitive behaviours. The growing body of evidence points to a role for cerebellar changes in ASD pathology. Some of the findings suggest that not only motor...

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Autores principales: Gąssowska-Dobrowolska, Magdalena, Kolasa, Agnieszka, Beversdorf, David Q., Adamczyk, Agata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776106/
https://www.ncbi.nlm.nih.gov/pubmed/36551785
http://dx.doi.org/10.3390/biomedicines10123031
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author Gąssowska-Dobrowolska, Magdalena
Kolasa, Agnieszka
Beversdorf, David Q.
Adamczyk, Agata
author_facet Gąssowska-Dobrowolska, Magdalena
Kolasa, Agnieszka
Beversdorf, David Q.
Adamczyk, Agata
author_sort Gąssowska-Dobrowolska, Magdalena
collection PubMed
description Autism spectrum disorders (ASD) are neurodevelopmental diseases characterised by deficits in social communication, restricted interests, and repetitive behaviours. The growing body of evidence points to a role for cerebellar changes in ASD pathology. Some of the findings suggest that not only motor problems but also social deficits, repetitive behaviours, and mental inflexibility associated with ASD are connected with damage to the cerebellum. However, the understanding of this brain structure’s functions in ASD pathology needs future investigations. Therefore, in this study, we generated a rodent model of ASD through a single prenatal administration of valproic acid (VPA) into pregnant rats, followed by cerebellar morphological studies of the offspring, focusing on the alterations of key cytoskeletal elements. The expression (Western blot) of α/β-tubulin and the major neuronal MT-associated proteins (MAP) such as MAP-Tau and MAP1B, MAP2, MAP6 (STOP) along with actin-crosslinking αII-spectrin and neurofilament light polypeptide (NF-L) was investigated. We found that maternal exposure to VPA induces a significant decrease in the protein levels of α/β-tubulin, MAP-Tau, MAP1B, MAP2, and αII-spectrin. Moreover, excessive MAP-Tau phosphorylation at (Ser396) along with key Tau-kinases activation was indicated. Immunohistochemical staining showed chromatolysis in the cerebellum of autistic-like rats and loss of Purkinje cells shedding light on one of the possible molecular mechanisms underpinning neuroplasticity alterations in the ASD brain.
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spelling pubmed-97761062022-12-23 Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders Gąssowska-Dobrowolska, Magdalena Kolasa, Agnieszka Beversdorf, David Q. Adamczyk, Agata Biomedicines Article Autism spectrum disorders (ASD) are neurodevelopmental diseases characterised by deficits in social communication, restricted interests, and repetitive behaviours. The growing body of evidence points to a role for cerebellar changes in ASD pathology. Some of the findings suggest that not only motor problems but also social deficits, repetitive behaviours, and mental inflexibility associated with ASD are connected with damage to the cerebellum. However, the understanding of this brain structure’s functions in ASD pathology needs future investigations. Therefore, in this study, we generated a rodent model of ASD through a single prenatal administration of valproic acid (VPA) into pregnant rats, followed by cerebellar morphological studies of the offspring, focusing on the alterations of key cytoskeletal elements. The expression (Western blot) of α/β-tubulin and the major neuronal MT-associated proteins (MAP) such as MAP-Tau and MAP1B, MAP2, MAP6 (STOP) along with actin-crosslinking αII-spectrin and neurofilament light polypeptide (NF-L) was investigated. We found that maternal exposure to VPA induces a significant decrease in the protein levels of α/β-tubulin, MAP-Tau, MAP1B, MAP2, and αII-spectrin. Moreover, excessive MAP-Tau phosphorylation at (Ser396) along with key Tau-kinases activation was indicated. Immunohistochemical staining showed chromatolysis in the cerebellum of autistic-like rats and loss of Purkinje cells shedding light on one of the possible molecular mechanisms underpinning neuroplasticity alterations in the ASD brain. MDPI 2022-11-24 /pmc/articles/PMC9776106/ /pubmed/36551785 http://dx.doi.org/10.3390/biomedicines10123031 Text en © 2022 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
Gąssowska-Dobrowolska, Magdalena
Kolasa, Agnieszka
Beversdorf, David Q.
Adamczyk, Agata
Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders
title Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders
title_full Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders
title_fullStr Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders
title_full_unstemmed Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders
title_short Alterations in Cerebellar Microtubule Cytoskeletal Network in a ValproicAcid-Induced Rat Model of Autism Spectrum Disorders
title_sort alterations in cerebellar microtubule cytoskeletal network in a valproicacid-induced rat model of autism spectrum disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776106/
https://www.ncbi.nlm.nih.gov/pubmed/36551785
http://dx.doi.org/10.3390/biomedicines10123031
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