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Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice

Neurological abnormalities, such as Parkinson-like disorders (PlD), are often co-morbidities of Type 2 Diabetic (T2D) patients, although the epidemiological link between these two disorders remains controversial. The PED/PEA-15 protein represents a possible candidate linking T2D and PD, because it i...

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Autores principales: Perruolo, Giuseppe, Viggiano, Davide, Fiory, Francesca, Cassese, Angela, Nigro, Cecilia, Liotti, Antonietta, Miele, Claudia, Beguinot, Francesco, Formisano, Pietro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947959/
https://www.ncbi.nlm.nih.gov/pubmed/27426254
http://dx.doi.org/10.1038/srep29967
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author Perruolo, Giuseppe
Viggiano, Davide
Fiory, Francesca
Cassese, Angela
Nigro, Cecilia
Liotti, Antonietta
Miele, Claudia
Beguinot, Francesco
Formisano, Pietro
author_facet Perruolo, Giuseppe
Viggiano, Davide
Fiory, Francesca
Cassese, Angela
Nigro, Cecilia
Liotti, Antonietta
Miele, Claudia
Beguinot, Francesco
Formisano, Pietro
author_sort Perruolo, Giuseppe
collection PubMed
description Neurological abnormalities, such as Parkinson-like disorders (PlD), are often co-morbidities of Type 2 Diabetic (T2D) patients, although the epidemiological link between these two disorders remains controversial. The PED/PEA-15 protein represents a possible candidate linking T2D and PD, because it is increased in subjects with T2D and is highly expressed in the brain. To test this hypothesis, we have analyzed the neurological and neurochemical phenotype of transgenic mice overexpressing PED/PEA-15 (tgPED). These mice develop impaired glucose tolerance and insulin resistance, accompanied by neurological features resembling PlD: feet clasping, slow and delayed locomotor movements in different behavioral tests in absence of clear cognitive deficits, ataxia or anxiety. Morphological analysis of the brains showed selective modifications of metabolic activity in the striatal region. In the same region, we have observed 26% decrease of dopamine fibers, confirmed by immunohistochemistry and Western Blot for tyrosine hydroxylase. Moreover, they also showed 48% reduction of dopamine levels in the striatum. Thus the tgPED mice may represent a genetic animal model of neurological disease linked to T2D.
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spelling pubmed-49479592016-07-26 Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice Perruolo, Giuseppe Viggiano, Davide Fiory, Francesca Cassese, Angela Nigro, Cecilia Liotti, Antonietta Miele, Claudia Beguinot, Francesco Formisano, Pietro Sci Rep Article Neurological abnormalities, such as Parkinson-like disorders (PlD), are often co-morbidities of Type 2 Diabetic (T2D) patients, although the epidemiological link between these two disorders remains controversial. The PED/PEA-15 protein represents a possible candidate linking T2D and PD, because it is increased in subjects with T2D and is highly expressed in the brain. To test this hypothesis, we have analyzed the neurological and neurochemical phenotype of transgenic mice overexpressing PED/PEA-15 (tgPED). These mice develop impaired glucose tolerance and insulin resistance, accompanied by neurological features resembling PlD: feet clasping, slow and delayed locomotor movements in different behavioral tests in absence of clear cognitive deficits, ataxia or anxiety. Morphological analysis of the brains showed selective modifications of metabolic activity in the striatal region. In the same region, we have observed 26% decrease of dopamine fibers, confirmed by immunohistochemistry and Western Blot for tyrosine hydroxylase. Moreover, they also showed 48% reduction of dopamine levels in the striatum. Thus the tgPED mice may represent a genetic animal model of neurological disease linked to T2D. Nature Publishing Group 2016-07-18 /pmc/articles/PMC4947959/ /pubmed/27426254 http://dx.doi.org/10.1038/srep29967 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Perruolo, Giuseppe
Viggiano, Davide
Fiory, Francesca
Cassese, Angela
Nigro, Cecilia
Liotti, Antonietta
Miele, Claudia
Beguinot, Francesco
Formisano, Pietro
Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice
title Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice
title_full Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice
title_fullStr Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice
title_full_unstemmed Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice
title_short Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice
title_sort parkinson-like phenotype in insulin-resistant ped/pea-15 transgenic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947959/
https://www.ncbi.nlm.nih.gov/pubmed/27426254
http://dx.doi.org/10.1038/srep29967
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