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Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease

In a preceding study, we showed that in adult pink1(−/−) mice, a monogenic animal model of Parkinson’s disease (PD), striatal neurons display aberrant electrical activities that precede the onset of overt clinical manifestations. Here, we tested the hypothesis that the maturation of dopaminergic (DA...

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Autores principales: Pearlstein, Edouard, Michel, François J., Save, Laurène, Ferrari, Diana C., Hammond, Constance
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917553/
https://www.ncbi.nlm.nih.gov/pubmed/27445695
http://dx.doi.org/10.3389/fncel.2016.00168
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author Pearlstein, Edouard
Michel, François J.
Save, Laurène
Ferrari, Diana C.
Hammond, Constance
author_facet Pearlstein, Edouard
Michel, François J.
Save, Laurène
Ferrari, Diana C.
Hammond, Constance
author_sort Pearlstein, Edouard
collection PubMed
description In a preceding study, we showed that in adult pink1(−/−) mice, a monogenic animal model of Parkinson’s disease (PD), striatal neurons display aberrant electrical activities that precede the onset of overt clinical manifestations. Here, we tested the hypothesis that the maturation of dopaminergic (DA) neurons of the pink1(−/−) substantia nigra compacta (SNc) follows, from early stages on, a different developmental trajectory from age-matched wild type (wt) SNc DA neurons. We used immature (postnatal days P2–P10) and young adult (P30–P90) midbrain slices of pink1(−/−) mice expressing the green fluorescent protein in tyrosine hydroxylase (TH)-positive neurons. We report that the developmental sequence of N-Methyl-D-aspartic acid (NMDA) spontaneous excitatory postsynaptic currents (sEPSCs) is altered in pink1(−/−) SNc DA neurons, starting from shortly after birth. They lack the transient episode of high NMDA receptor-mediated neuronal activity characteristic of the immature stage of wt SNc DA neurons. The maturation of the membrane resistance of pink1(−/−) SNc DA neurons is also altered. Collectively, these observations suggest that electrical manifestations occurring shortly after birth in SNc DA neurons might lead to dysfunction in dopamine release and constitute an early pathogenic mechanism of PD.
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spelling pubmed-49175532016-07-21 Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease Pearlstein, Edouard Michel, François J. Save, Laurène Ferrari, Diana C. Hammond, Constance Front Cell Neurosci Neuroscience In a preceding study, we showed that in adult pink1(−/−) mice, a monogenic animal model of Parkinson’s disease (PD), striatal neurons display aberrant electrical activities that precede the onset of overt clinical manifestations. Here, we tested the hypothesis that the maturation of dopaminergic (DA) neurons of the pink1(−/−) substantia nigra compacta (SNc) follows, from early stages on, a different developmental trajectory from age-matched wild type (wt) SNc DA neurons. We used immature (postnatal days P2–P10) and young adult (P30–P90) midbrain slices of pink1(−/−) mice expressing the green fluorescent protein in tyrosine hydroxylase (TH)-positive neurons. We report that the developmental sequence of N-Methyl-D-aspartic acid (NMDA) spontaneous excitatory postsynaptic currents (sEPSCs) is altered in pink1(−/−) SNc DA neurons, starting from shortly after birth. They lack the transient episode of high NMDA receptor-mediated neuronal activity characteristic of the immature stage of wt SNc DA neurons. The maturation of the membrane resistance of pink1(−/−) SNc DA neurons is also altered. Collectively, these observations suggest that electrical manifestations occurring shortly after birth in SNc DA neurons might lead to dysfunction in dopamine release and constitute an early pathogenic mechanism of PD. Frontiers Media S.A. 2016-06-23 /pmc/articles/PMC4917553/ /pubmed/27445695 http://dx.doi.org/10.3389/fncel.2016.00168 Text en Copyright © 2016 Pearlstein, Michel, Save, Ferrari and Hammond. 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 and reproduction in other forums is permitted, provided the original author(s) or licensor 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
Pearlstein, Edouard
Michel, François J.
Save, Laurène
Ferrari, Diana C.
Hammond, Constance
Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease
title Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease
title_full Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease
title_fullStr Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease
title_full_unstemmed Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease
title_short Abnormal Development of Glutamatergic Synapses Afferent to Dopaminergic Neurons of the Pink1(−/−) Mouse Model of Parkinson’s Disease
title_sort abnormal development of glutamatergic synapses afferent to dopaminergic neurons of the pink1(−/−) mouse model of parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917553/
https://www.ncbi.nlm.nih.gov/pubmed/27445695
http://dx.doi.org/10.3389/fncel.2016.00168
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