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In vivo imaging of brain glutamate defects in a knock-in mouse model of Huntington's disease

Jérémy Pépin, Laetitia Francelle, Maria-Angeles Carrillo-de Sauvage, Lucie de Longprez, Pauline Gipchtein, Karine Cambon, Julien Valette, Emmanuel Brouillet, Julien Flament
2016 NeuroImage  
In this study, we used Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) in order to map glutamate distribution in the brain of a knock-in mouse model (Ki140CAG) with a precise anatomical  ...  We evaluated for the first time gluCEST imaging as a potential biomarker of HD and demonstrated its potential for characterizing metabolic defects in neurodegenerative diseases in specific regions.  ...  Humbert for their help in getting the breeders for starting our Ki140CAG mouse colony. We are grateful J. Mitja for taking care of the animal and helping with behavioral studies.  ... 
doi:10.1016/j.neuroimage.2016.06.023 pmid:27318215 fatcat:burejlh4mbednd777yjafcj5qi

Mitochondria in Huntington's disease

Maria Damiano, Laurie Galvan, Nicole Déglon, Emmanuel Brouillet
2010 Biochimica et Biophysica Acta - Molecular Basis of Disease  
The disease is caused by an abnormal expansion of a CAG repeat located in exon 1 of the gene encoding the huntingtin protein (Htt) that confers a toxic function to the protein.  ...  Striatal neurons may be particularly vulnerable to these defects. One hypothesis is that neurotransmission systems such as dopamine and glutamate exacerbate mitochondrial defects in the striatum.  ...  In vivo experiments also support a role for dopamine and its receptors in HD pathogenesis: DAT (dopamine transporter) knock-out (KO) mice crossed with a knock-in transgenic mouse model of HD showed enhanced  ... 
doi:10.1016/j.bbadis.2009.07.012 pmid:19682570 fatcat:u5bvfqqnqbcf3ehg6pf3fnzk44

Cortical and Striatal Circuits in Huntington's Disease

Sonja Blumenstock, Irina Dudanova
2020 Frontiers in Neuroscience  
In particular, in vivo imaging studies in mouse HD models have demonstrated early structural and functional disturbances within the cortical network, and optogenetic manipulations of striatal cell types  ...  Huntington's disease (HD) is a hereditary neurodegenerative disorder that typically manifests in midlife with motor, cognitive, and/or psychiatric symptoms.  ...  FUNDING We acknowledge funding from the European Research Council (grant FP7 GA ERC-2012-SyG_318987-ToPAG) and from the Max Planck Society for the Advancement of Science.  ... 
doi:10.3389/fnins.2020.00082 pmid:32116525 pmcid:PMC7025546 fatcat:z2cvf6ipsvd4ljw3vlnsgxoudq

Huntington's disease mouse models: unraveling the pathology caused by CAG repeat expansion

Julia Kaye, Terry Reisine, Steve Finkbeiner
2021 Faculty Reviews  
Huntington's disease (HD) is a neurodegenerative disease that results in motor and cognitive dysfunction, leading to early death.  ...  The first and best-studied in vivo rodent model of HD is the R6/2 mouse, in which a transgene containing the promoter and exon 1 fragment of human HTT with 150 CAG repeats was inserted into the mouse genome  ...  Marie-Francoise Chesselet (Emeritus Professor at UCLA, CA) and all members of the Finkbeiner lab.  ... 
doi:10.12703/r/10-77 pmid:34746930 pmcid:PMC8546598 fatcat:hd5jod3kmvfwnlpab5pkddk7lu

Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington's disease mice

Junghee Lee, Bela Kosaras, Steve J. Del Signore, Kerry Cormier, Ann McKee, Rajiv R. Ratan, Neil W. Kowall, Hoon Ryu
2010 Acta Neuropathologica  
In the present study, we found a marked increase of 4-hydroxy-2-nonenal (4-HNE) adducts, a lipid peroxidation marker, in the caudate and putamen of HD brains and in the striatum of HD mice.  ...  Keywords Huntington's disease Á Mitochondria Á Lipid peroxidation Á 4-Hydroxy-2-nonenal (4-HNE) Á Neuronal survival Electronic supplementary material The online version of this article (  ...  Acknowledgments We thank to Katharine Karr and Yu Jin Hwang for the preparation of manuscript. This study was supported by NIH NS52724 (H.R.).  ... 
doi:10.1007/s00401-010-0788-5 pmid:21161248 pmcid:PMC3151672 fatcat:eufwr3uss5fclm5r3mn3fwubie

Cell Therapy in Huntington's Disease [chapter]

Hyun Sook Kim, Jihwan Song
2015 Progress in Stem Cell Transplantation  
Huntington's disease HD is a rare neurodegenerative disease inherited in an autosomal dominant pattern.  ...  "ecause clinical trials performed using human fetal striatal cells have shown variable outcomes, future directions of cell therapy in HD should consider the reconstitution of a functional dynamic information-processing  ...  Acknowledgements This work was supported by a grant of the "asic Science Research Program through the National Research Foundation of Korea NRF funded by the Ministry of Education, Science, and Technology  ... 
doi:10.5772/60618 fatcat:s2zowfkjtva6lk3sxvo3wtwwdq

Genetically encoded fluorescent sensors for studying healthy and diseased nervous systems

Lin Tian, Loren L. Looger
2008 Drug Discovery Today : Disease Models  
Optical imaging techniques allow the direct visualization of individual neurons in a circuit environment.  ...  Sensor analysis in healthy and diseased brains may reveal important differences and shed light on the development and progression of nervous system disorders.  ...  Acknowledgments We would like to give special thanks to members of the Looger laboratory for comments and critical reading of the manuscript.  ... 
doi:10.1016/j.ddmod.2008.07.003 pmid:19461949 pmcid:PMC2651031 fatcat:mu5txpcup5h4ndg4yuq4xu6ct4

Mitochondrial calcium function and dysfunction in the central nervous system

David G. Nicholls
2009 Biochimica et Biophysica Acta - Bioenergetics  
stroke, while the neurodegenerative disease in which possible defects in mitochondrial Ca 2+ handling have been most intensively investigated is Huntington's Disease.  ...  in rapidly frozen Ca 2+ -loaded brain mitochondria and reported a variable calcium to phosphate ratio depending on loading conditions, suggesting that the composition of the complex is somewhat flexible  ...  Acknowledgements Recent work from the author's laboratory mentioned in this review was supported by grants from the NIA AG032118, and 1 PO1 AG025901.  ... 
doi:10.1016/j.bbabio.2009.03.010 pmid:19298790 pmcid:PMC2752662 fatcat:nymb3qp72bdvrmcxgyz5qmom2i

Molecular insights into cortico-striatal miscommunications in Huntington's disease

Matthew B Veldman, X William Yang
2018 Current Opinion in Neurobiology  
Huntington's disease (HD), a dominantly inherited neurodegenerative disease, is defined by its genetic cause, a CAG-repeat expansion in the HTT gene, its motor and psychiatric symptomology and primary  ...  Mouse models of HD have been created that exhibit phenotypes reminiscent of those in the patient, and specifically, cortico-striatal disconnectivity appears to be a shared pathogenic event shared by HD  ...  Acknowledgments We thank Peter Langfelder and Fuying Gao for help in bioinformatics, and members of the Yang lab for thoughtful discussions and support of this review.  ... 
doi:10.1016/j.conb.2017.10.019 pmid:29125980 pmcid:PMC5825262 fatcat:yly3gjzbwjaovi76idd3ea3gr4

HDAC4 Reduction: A Novel Therapeutic Strategy to Target Cytoplasmic Huntingtin and Ameliorate Neurodegeneration

Michal Mielcarek, Christian Landles, Andreas Weiss, Amyaouch Bradaia, Tamara Seredenina, Linda Inuabasi, Georgina F. Osborne, Kristian Wadel, Chrystelle Touller, Rachel Butler, Janette Robertson, Sophie A. Franklin (+10 others)
2013 PLoS Biology  
We hypothesised that it may be involved in the molecular pathogenesis of Huntington's disease (HD), a protein-folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion in  ...  We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels, and rescued neuronal and cortico-striatal synaptic function in HD mouse models.  ...  Acknowledgments We thank Caroline Benn, Agnesska Benjamin, Marie Bondulich, Helen Fox, Hayley Lazell, Oliver Pressey, Sunny Sunshine, Ben Woodman, Dan Goodwin, Dorothee Abramowski, and Sabine Kauffmann for mouse  ... 
doi:10.1371/journal.pbio.1001717 pmid:24302884 pmcid:PMC3841096 fatcat:5cmjtfjuang7ljnrvdgawjb264

Identification of the key role of white matter alteration in the pathogenesis of Huntington's Disease [article]

Jean-Baptiste Perot, Marina Celestine, Marco Palombo, Marc Dhenain, Sandrine Humbert, Emmanuel Brouillet, Julien Flament
2021 bioRxiv   pre-print
imaging, in order to assess white matter integrity over the life of this very progressive mouse model.  ...  Pathogenesis of the inherited neurodegenerative disorder Huntington s Disease (HD) is complex and progressive, with a long presymptomatic phase in which subtle changes occur in the brain of gene carriers  ...  The Ki140CAG mouse model 53 is a knock-in model of HD containing 140 CAG repeats inserted in the murine huntingtin gene.  ... 
doi:10.1101/2021.06.21.449242 fatcat:55jvlpejufdmzdvuhl36blyq7e

Metabolic Disturbances in Diseases with Neurological Involvement

2014 Aging and Disease  
Data from patients and animal models evidenced that energy dysfunction may play a role in the pathophysiology of the characteristic brain damage found in these diseases.  ...  It should, however, emphasized that the mitochondrial involvement linked to the pathophysiology of neurodegenderative diseases is not restricted to defects in energy metabolism and DNA mutations, but also  ...  measured in vivo from MR images [210] .  ... 
doi:10.14336/ad.2014.0500238 pmid:25110608 pmcid:PMC4113514 fatcat:fjzv47qd5bh4pcaswd6wh6taga

Molecular Mechanisms and Potential Therapeutical Targets in Huntington's Disease

Chiara Zuccato, Marta Valenza, Elena Cattaneo
2010 Physiological Reviews  
General Introduction to Huntington's Disease A. Historical background B. Neuropathology C. Symptoms D. Gene hunters E. Genetic modifiers of HD F. Modeling HD III. The Normal Function of Huntingtin A.  ...  Biomarkers in Huntington's Disease A. Imaging studies B. Metabolomic, proteomic, and transcriptomic approaches C. Biomarkers built on Hypothesis-Driven experiments IX. Conclusions  ...  in a knock-in mouse model of HD (HdhQ111) compared with a knock-in mouse model expressing only 18 CAG (HdhQ18).  ... 
doi:10.1152/physrev.00041.2009 pmid:20664076 fatcat:x34xcxbgvrcyxgzjohy67b5zoy

Dysfunction of Mitochondrial Ca2+ Regulatory Machineries in Brain Aging and Neurodegenerative Diseases

Hyunsu Jung, Su Yeon Kim, Fatma Sema Canbakis Cecen, Yongcheol Cho, Seok-Kyu Kwon
2020 Frontiers in Cell and Developmental Biology  
During brain aging and the progress of neurodegenerative disease, mitochondrial Ca2+ mishandling has been observed using various techniques, including live imaging of Ca2+ dynamics.  ...  Here, we discuss current research into mitochondrial Ca2+ regulatory machineries and how mitochondrial Ca2+ dysregulation contributes to brain aging and neurodegenerative disease.  ...  In-vivo Ca 2+ imaging with mitochondriatargeted Förster resonance energy transfer (FRET)-based GECI has directly demonstrated an Aβ-dependent mitochondrial Ca 2+ increase in mouse cortex.  ... 
doi:10.3389/fcell.2020.599792 pmid:33392190 pmcid:PMC7775422 fatcat:k5svaejc2ze5dare66ft3xfutu

Mutant Huntingtin Impairs BDNF Release from Astrocytes by Disrupting Conversion of Rab3a-GTP into Rab3a-GDP

Y. Hong, T. Zhao, X.-J. Li, S. Li
2016 Journal of Neuroscience  
We know that BDNF levels decline in the brains of patients with Huntington's disease (HD), a neurodegenerative disease caused by the expression of mutant huntingtin protein (mHtt), and furthermore that  ...  rescue this deficient BDNF release and early neuropathology in HD knock-in mouse brain.  ...  We used both full-length HD140Q knock-in (KI) and GFAP-Htt transgenic (TG) mouse models to investigate the effect of mHtt on astrocytic BDNF.  ... 
doi:10.1523/jneurosci.0168-16.2016 pmid:27559163 pmcid:PMC4995297 fatcat:rc62f6ptorex5fbvpojbkgfyha
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