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Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease

Twelve-month-old male mice expressing the human A53T variant of α-synuclein (A53T) develop dopamine neuron degeneration, neuroinflammation, and motor deficits, along with dysfunctions of the mitochondrial Na(+)-Ca(2+) exchanger (NCX) isoforms 1 (NCX1) and 3 (NCX3) in the nigrostriatal system. Since...

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Autores principales: Costa, Giulia, Sisalli, Maria Jose, Simola, Nicola, Della Notte, Salvatore, Casu, Maria Antonietta, Serra, Marcello, Pinna, Annalisa, Feliciello, Antonio, Annunziato, Lucio, Scorziello, Antonella, Morelli, Micaela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232579/
https://www.ncbi.nlm.nih.gov/pubmed/32477098
http://dx.doi.org/10.3389/fnagi.2020.00118
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author Costa, Giulia
Sisalli, Maria Jose
Simola, Nicola
Della Notte, Salvatore
Casu, Maria Antonietta
Serra, Marcello
Pinna, Annalisa
Feliciello, Antonio
Annunziato, Lucio
Scorziello, Antonella
Morelli, Micaela
author_facet Costa, Giulia
Sisalli, Maria Jose
Simola, Nicola
Della Notte, Salvatore
Casu, Maria Antonietta
Serra, Marcello
Pinna, Annalisa
Feliciello, Antonio
Annunziato, Lucio
Scorziello, Antonella
Morelli, Micaela
author_sort Costa, Giulia
collection PubMed
description Twelve-month-old male mice expressing the human A53T variant of α-synuclein (A53T) develop dopamine neuron degeneration, neuroinflammation, and motor deficits, along with dysfunctions of the mitochondrial Na(+)-Ca(2+) exchanger (NCX) isoforms 1 (NCX1) and 3 (NCX3) in the nigrostriatal system. Since gender is thought to play a role in the etiology of Parkinson’s disease (PD), we characterized neurochemical and behavioral alterations in 12-month-old female A53T transgenic mice. We investigated the presence of dopaminergic degeneration, astrogliosis and microgliosis using immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (IBA-1) in both the substantia nigra pars compacta (SNc) and striatum. In the same regions, we also evaluated the co-localization of NCX1 in cells positive for IBA-1 and the co-localization of NCX3 in TH-positive neurons and fibers. Furthermore, in both male and female mice, we performed motor (beam walking and pole tests) and memory [novel object recognition (NOR) and spontaneous alternation] tasks, together with tests to evaluate peripheral deficits (olfactory and stool collection tests). Female A53T transgenic mice displayed degeneration of nigral dopaminergic neurons, but neither microgliosis nor astrogliosis in the SNc and striatum. Moreover, female A53T transgenic mice displayed co-localization between NCX1 and IBA-1 positive cells in the striatum but not SNc, whereas NCX3 did not co-localize with either TH-positive terminals or neuronal bodies in the nigrostriatal system. Furthermore, female A53T transgenic mice showed increased crossing time in the beam walking test, but no impairments in the pole or memory tests, and in tests that evaluated peripheral deficits, whereas male A53T transgenic mice displayed motor, memory and peripheral deficits. Immunohistochemical and behavioral results obtained here in the female mice differ from those previously observed in males, and suggest a dissimilar influence of NCX1 and NCX3 on dopaminergic function in female and male A53T transgenic mice, strengthening the validity of these mice as a model for studying the etiological factors of PD.
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spelling pubmed-72325792020-05-29 Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease Costa, Giulia Sisalli, Maria Jose Simola, Nicola Della Notte, Salvatore Casu, Maria Antonietta Serra, Marcello Pinna, Annalisa Feliciello, Antonio Annunziato, Lucio Scorziello, Antonella Morelli, Micaela Front Aging Neurosci Neuroscience Twelve-month-old male mice expressing the human A53T variant of α-synuclein (A53T) develop dopamine neuron degeneration, neuroinflammation, and motor deficits, along with dysfunctions of the mitochondrial Na(+)-Ca(2+) exchanger (NCX) isoforms 1 (NCX1) and 3 (NCX3) in the nigrostriatal system. Since gender is thought to play a role in the etiology of Parkinson’s disease (PD), we characterized neurochemical and behavioral alterations in 12-month-old female A53T transgenic mice. We investigated the presence of dopaminergic degeneration, astrogliosis and microgliosis using immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (IBA-1) in both the substantia nigra pars compacta (SNc) and striatum. In the same regions, we also evaluated the co-localization of NCX1 in cells positive for IBA-1 and the co-localization of NCX3 in TH-positive neurons and fibers. Furthermore, in both male and female mice, we performed motor (beam walking and pole tests) and memory [novel object recognition (NOR) and spontaneous alternation] tasks, together with tests to evaluate peripheral deficits (olfactory and stool collection tests). Female A53T transgenic mice displayed degeneration of nigral dopaminergic neurons, but neither microgliosis nor astrogliosis in the SNc and striatum. Moreover, female A53T transgenic mice displayed co-localization between NCX1 and IBA-1 positive cells in the striatum but not SNc, whereas NCX3 did not co-localize with either TH-positive terminals or neuronal bodies in the nigrostriatal system. Furthermore, female A53T transgenic mice showed increased crossing time in the beam walking test, but no impairments in the pole or memory tests, and in tests that evaluated peripheral deficits, whereas male A53T transgenic mice displayed motor, memory and peripheral deficits. Immunohistochemical and behavioral results obtained here in the female mice differ from those previously observed in males, and suggest a dissimilar influence of NCX1 and NCX3 on dopaminergic function in female and male A53T transgenic mice, strengthening the validity of these mice as a model for studying the etiological factors of PD. Frontiers Media S.A. 2020-05-07 /pmc/articles/PMC7232579/ /pubmed/32477098 http://dx.doi.org/10.3389/fnagi.2020.00118 Text en Copyright © 2020 Costa, Sisalli, Simola, Della Notte, Casu, Serra, Pinna, Feliciello, Annunziato, Scorziello and Morelli. http://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 Neuroscience
Costa, Giulia
Sisalli, Maria Jose
Simola, Nicola
Della Notte, Salvatore
Casu, Maria Antonietta
Serra, Marcello
Pinna, Annalisa
Feliciello, Antonio
Annunziato, Lucio
Scorziello, Antonella
Morelli, Micaela
Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease
title Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease
title_full Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease
title_fullStr Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease
title_full_unstemmed Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease
title_short Gender Differences in Neurodegeneration, Neuroinflammation and Na(+)-Ca(2+) Exchangers in the Female A53T Transgenic Mouse Model of Parkinson’s Disease
title_sort gender differences in neurodegeneration, neuroinflammation and na(+)-ca(2+) exchangers in the female a53t transgenic mouse model of parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232579/
https://www.ncbi.nlm.nih.gov/pubmed/32477098
http://dx.doi.org/10.3389/fnagi.2020.00118
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