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Real-time imaging of glutamate clearance reveals normal striatal uptake in Huntington disease mouse models.
- Source :
-
Nature communications [Nat Commun] 2016 Apr 07; Vol. 7, pp. 11251. Date of Electronic Publication: 2016 Apr 07. - Publication Year :
- 2016
-
Abstract
- It has become well accepted that Huntington disease (HD) is associated with impaired glutamate uptake, resulting in a prolonged time-course of extracellular glutamate that contributes to excitotoxicity. However, the data supporting this view come largely from work in synaptosomes, which may overrepresent nerve-terminal uptake over astrocytic uptake. Here, we quantify real-time glutamate dynamics in HD mouse models by high-speed imaging of an intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) and electrophysiological recordings of synaptically activated transporter currents in astrocytes. These techniques reveal a disconnect between the results obtained in synaptosomes and those in situ. Exogenous glutamate uptake is impaired in synaptosomes, whereas real-time measures of glutamate clearance in the HD striatum are normal or even accelerated, particularly in the aggressive R6/2 model. Our results highlight the importance of quantifying glutamate dynamics under endogenous release conditions, and suggest that the widely cited uptake impairment in HD does not contribute to pathogenesis.
- Subjects :
- Animals
Astrocytes pathology
Biological Transport
Corpus Striatum pathology
Dependovirus genetics
Disease Models, Animal
Genes, Reporter
Genetic Vectors
Humans
Huntington Disease pathology
Male
Membrane Potentials physiology
Mice
Mice, Transgenic
Synaptosomes metabolism
Astrocytes metabolism
Corpus Striatum metabolism
Glutamic Acid metabolism
Huntington Disease metabolism
Optical Imaging methods
Synapses metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 27052848
- Full Text :
- https://doi.org/10.1038/ncomms11251