Web of Science: 5 citations, Scopus: 6 citations, Google Scholar: citations,
Loss of mitochondrial Ndufs4 in striatal medium spiny neurons mediates progressive motor impairment in a mouse model of leigh syndrome
Chen, Byron (University of Washington. Howard Hughes Medical Institute)
Hui, Jessica (Seattle Children's Research Institute (Seattle, Estats Units d'Amèrica))
Montgomery, Kelsey S. (Universitat Autònoma de Barcelona. Institut de Neurociències)
Gella, Alejandro (Universitat Autònoma de Barcelona. Institut de Neurociències)
Bolea Tomás, Irene (Universitat Autònoma de Barcelona. Institut de Neurociències)
Sanz Iglesias, Elisenda (Universitat Autònoma de Barcelona. Institut de Neurociències)
Palmiter, Richard D. (Howard Hughes Medical Institute (Maryland, Estats Units d'Amèrica))
Quintana Romero, Albert (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date: 2017
Abstract: Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4, a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs), which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.
Note: Altres ajuts: Juan del la Cierva (IJCI-2015-24576)
Note: Número d'acord de subvenció EC/H2020/658352
Note: Número d'acord de subvenció EC/H2020/665919
Note: Número d'acord de subvenció EC/H2020/638106
Note: Número d'acord de subvenció MINECO/SAF2014-57981P
Note: Número d'acord de subvenció MINECO/RyC-2012-11873
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: Animal ; Behavior ; Medium spiny neuron ; Mitochondrial disease ; Mouse genetics ; Striatum
Published in: Frontiers in molecular neuroscience, Vol. 10 (August 2017) , article 265, ISSN 1662-5099

DOI: 10.3389/fnmol.2017.00265
PMID: 28883788

8 p, 2.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2017-12-05, last modified 2020-08-09

   Favorit i Compartir