In Vivo MRI Evidence that Neuropathology is Attenuated by Cognitive Enrichment in the Yac128 Huntington’s Disease Mouse Model

2015 ◽  
Vol 4 (2) ◽  
pp. 149-160 ◽  
Author(s):  
Jessica J. Steventon ◽  
David J. Harrison ◽  
Rebecca C. Trueman ◽  
Anne E. Rosser ◽  
Derek K. Jones ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Enrichment

scholarly journals Elevated Type 1 Metabotropic Glutamate Receptor Availability in a Mouse Model of Huntington’s Disease: a Longitudinal PET Study

2020 ◽  
Vol 57 (4) ◽  
pp. 2038-2047 ◽  
Author(s):  
Daniele Bertoglio ◽  
Jeroen Verhaeghe ◽  
Špela Korat ◽  
Alan Miranda ◽  
Klaudia Cybulska ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Pet Imaging ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Post Mortem ◽  
Metabotropic Glutamate ◽  
Group I

AbstractImpairment of group I metabotropic glutamate receptors (mGluRs) results in altered glutamate signalling, which is associated with several neurological disorders including Huntington’s Disease (HD), an autosomal neurodegenerative disease. In this study, we assessed in vivo pathological changes in mGluR1 availability in the Q175DN mouse model of HD using longitudinal positron emission tomography (PET) imaging with the radioligand [11C]ITDM. Ninety-minute dynamic PET imaging scans were performed in 22 heterozygous (HET) Q175DN mice and 22 wild-type (WT) littermates longitudinally at 6, 12, and 16 months of age. Analyses of regional volume of distribution with an image-derived input function (VT (IDIF)) and voxel-wise parametric VT (IDIF) maps were performed to assess differences between genotypes. Post-mortem evaluation at 16 months was done to support in vivo findings. [11C]ITDM VT (IDIF) quantification revealed higher mGluR1 availability in the brain of HET mice compared to WT littermates (e.g. cerebellum: + 15.0%, + 17.9%, and + 17.6% at 6, 12, and 16 months, respectively; p < 0.001). In addition, an age-related decline in [11C]ITDM binding independent of genotype was observed between 6 and 12 months. Voxel-wise analysis of parametric maps and post-mortem quantifications confirmed the elevated mGluR1 availability in HET mice compared to WT littermates. In conclusion, in vivo measurement of mGluR1 availability using longitudinal [11C]ITDM PET imaging demonstrated higher [11C]ITDM binding in extra-striatal brain regions during the course of disease in the Q175DN mouse model.

scholarly journals The longevity-associated variant of BPIFB4 improves a CXCR4-mediated striatum–microglia crosstalk preventing disease progression in a mouse model of Huntington’s disease

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Alba Di Pardo ◽  
Elena Ciaglia ◽  
Monica Cattaneo ◽  
Anna Maciag ◽  
Francesco Montella ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Cag Repeats ◽  
Huntingtin Protein ◽  
Human Microglia

Abstract The longevity-associated variant (LAV) of the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been found significantly enriched in long-living individuals. Neuroinflammation is a key player in Huntington’s disease (HD), a neurodegenerative disorder caused by neural death due to expanded CAG repeats encoding a long polyglutamine tract in the huntingtin protein (Htt). Herein, we showed that striatal-derived cell lines with expanded Htt (STHdh Q111/111) expressed and secreted lower levels of BPIFB4, when compared with Htt expressing cells (STHdh Q7/7), which correlated with a defective stress response to proteasome inhibition. Overexpression of LAV-BPIFB4 in STHdh Q111/111 cells was able to rescue both the BPIFB4 secretory profile and the proliferative/survival response. According to a well-established immunomodulatory role of LAV-BPIFB4, conditioned media from LAV-BPIFB4-overexpressing STHdh Q111/111 cells were able to educate Immortalized Human Microglia—SV40 microglial cells. While STHdh Q111/111 dying cells were ineffective to induce a CD163 + IL-10high pro-resolving microglia compared to normal STHdh Q7/7, LAV-BPIFB4 transduction promptly restored the central immune control through a mechanism involving the stromal cell-derived factor-1. In line with the in vitro results, adeno-associated viral-mediated administration of LAV-BPIFB4 exerted a CXCR4-dependent neuroprotective action in vivo in the R6/2 HD mouse model by preventing important hallmarks of the disease including motor dysfunction, body weight loss, and mutant huntingtin protein aggregation. In this view, LAV-BPIFB4, due to its pleiotropic ability in both immune compartment and cellular homeostasis, may represent a candidate for developing new treatment for HD.

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

NeuroImage ◽  
2016 ◽  
Vol 139 ◽  
pp. 53-64 ◽  
Author(s):  
Jérémy Pépin ◽  
Laetitia Francelle ◽  
Maria-Angeles Carrillo-de Sauvage ◽  
Lucie de Longprez ◽  
Pauline Gipchtein ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
In Vivo Imaging

In vivo proof-of-concept of removal of the huntingtin caspase cleavage motif-encoding exon 12 approach in the YAC128 mouse model of Huntington’s disease

2016 ◽  
Vol 84 ◽  
pp. 93-96 ◽  
Author(s):  
João Casaca-Carreira ◽  
Lodewijk J.A. Toonen ◽  
Melvin M. Evers ◽  
Ali Jahanshahi ◽  
Willeke M.C. van-Roon-Mom ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Proof Of Concept ◽  
Caspase Cleavage ◽  
Yac128 Mouse ◽  
Cleavage Motif

scholarly journals SAHA Decreases HDAC 2 and 4 Levels In Vivo and Improves Molecular Phenotypes in the R6/2 Mouse Model of Huntington's Disease

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27746 ◽  
Author(s):  
Michal Mielcarek ◽  
Caroline L. Benn ◽  
Sophie A. Franklin ◽  
Donna L. Smith ◽  
Ben Woodman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Molecular Phenotypes

scholarly journals Loss of caveolin-1 expression in knock-in mouse model of Huntington's disease suppresses pathophysiology in vivo

2013 ◽  
Vol 23 (1) ◽  
pp. 129-144 ◽  
Author(s):  
Eugenia Trushina ◽  
Christie A. Canaria ◽  
Do-Yup Lee ◽  
Cynthia T. McMurray
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Caveolin 1

scholarly journals Longitudinal in vivo MRI in a Huntington’s disease mouse model: Global atrophy in the absence of white matter microstructural damage

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jessica J. Steventon ◽  
Rebecca C. Trueman ◽  
Da Ma ◽  
Emma Yhnell ◽  
Zubeyde Bayram-Weston ◽  
...  
Keyword(s):  
White Matter ◽  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Microstructural Damage

scholarly journals Nucleolar stress controls mutant Huntington toxicity and monitors Huntington’s disease progression

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Aynur Sönmez ◽  
Rasem Mustafa ◽  
Salome T. Ryll ◽  
Francesca Tuorto ◽  
Ludivine Wacheul ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Cellular Stress ◽  
Cag Repeats ◽  
Presymptomatic Stage ◽  
The Impact

AbstractTranscriptional and cellular-stress surveillance deficits are hallmarks of Huntington’s disease (HD), a fatal autosomal-dominant neurodegenerative disorder caused by a pathological expansion of CAG repeats in the Huntingtin (HTT) gene. The nucleolus, a dynamic nuclear biomolecular condensate and the site of ribosomal RNA (rRNA) transcription, is implicated in the cellular stress response and in protein quality control. While the exact pathomechanisms of HD are still unclear, the impact of nucleolar dysfunction on HD pathophysiology in vivo remains elusive. Here we identified aberrant maturation of rRNA and decreased translational rate in association with human mutant Huntingtin (mHTT) expression. The protein nucleophosmin 1 (NPM1), important for nucleolar integrity and rRNA maturation, loses its prominent nucleolar localization. Genetic disruption of nucleolar integrity in vulnerable striatal neurons of the R6/2 HD mouse model decreases the distribution of mHTT in a disperse state in the nucleus, exacerbating motor deficits. We confirmed NPM1 delocalization in the gradually progressing zQ175 knock-in HD mouse model: in the striatum at a presymptomatic stage and in the skeletal muscle at an early symptomatic stage. In Huntington’s patient skeletal muscle biopsies, we found a selective redistribution of NPM1, similar to that in the zQ175 model. Taken together, our study demonstrates that nucleolar integrity regulates the formation of mHTT inclusions in vivo, and identifies NPM1 as a novel, readily detectable peripheral histopathological marker of HD progression.

B40 In vivo imaging of brain glutamate defects in a knock-in mouse model of huntington’s disease

2016 ◽  
Vol 87 (Suppl 1) ◽  
pp. A23.2-A23
Author(s):  
Julien Flament ◽  
Jérémy Pépin ◽  
Laetitia Francelle ◽  
Maria-Angeles Carrillo-de Sauvage ◽  
Lucie de Longprez ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
In Vivo Imaging
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