Overexpression of BDNF and Full-Length TrkB Receptor Ameliorate Striatal Neural Survival in Huntington's Disease

2015 ◽  
Vol 15 (4) ◽  
pp. 207-218 ◽  
Author(s):  
Ana Silva ◽  
Luana Naia ◽  
Alejandro Dominguez ◽  
Márcio Ribeiro ◽  
Joana Rodrigues ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Full Length ◽  
Trkb Receptor ◽  
Neural Survival

scholarly journals Identification of Full-Length Wild-Type and Mutant Huntingtin Interacting Proteins by Crosslinking Immunoprecipitation in Mice Brain Cortex

2021 ◽  
pp. 1-13
Author(s):  
Karen A. Sap ◽  
Arzu Tugce Guler ◽  
Aleksandra Bury ◽  
Dick Dekkers ◽  
Jeroen A.A. Demmers ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Brain Cortex ◽  
Full Length ◽  
Biological Processes ◽  
Interacting Proteins ◽  
Mutant Huntingtin ◽  
Wild Type ◽  
Mutant Huntingtin Protein ◽  
Mice Brain

Background: Huntington’s disease is a neurodegenerative disorder caused by a CAG expansion in the huntingtin gene, resulting in a polyglutamine expansion in the ubiquitously expressed mutant huntingtin protein. Objective: Here we set out to identify proteins interacting with the full-length wild-type and mutant huntingtin protein in the mice cortex brain region to understand affected biological processes in Huntington’s disease pathology. Methods: Full-length huntingtin with 20 and 140 polyQ repeats were formaldehyde-crosslinked and isolated via their N-terminal Flag-tag from 2-month-old mice brain cortex. Interacting proteins were identified and quantified by label-free liquid chromatography-mass spectrometry (LC-MS/MS). Results: We identified 30 interactors specific for wild-type huntingtin, 14 interactors specific for mutant huntingtin and 14 shared interactors that interacted with both wild-type and mutant huntingtin, including known interactors such as F8a1/Hap40. Syt1, Ykt6, and Snap47, involved in vesicle transport and exocytosis, were among the proteins that interacted specifically with wild-type huntingtin. Various other proteins involved in energy metabolism and mitochondria were also found to associate predominantly with wild-type huntingtin, whereas mutant huntingtin interacted with proteins involved in translation including Mapk3, Eif3h and Eef1a2. Conclusion: Here we identified both shared and specific interactors of wild-type and mutant huntingtin, which are involved in different biological processes including exocytosis, vesicle transport, translation and metabolism. These findings contribute to the understanding of the roles that wild-type and mutant huntingtin play in a variety of cellular processes both in healthy conditions and Huntington’s disease pathology.

Full length huntingtin is not detected in intranuclear inclusions in Huntington's disease brain

1998 ◽  
Vol 26 (3) ◽  
pp. S243-S243 ◽  
Author(s):  
Philip Thomas ◽  
Fiona Wilkinson ◽  
Nguyen thi Man ◽  
Peter S Harper ◽  
James W Neal ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Full Length ◽  
Intranuclear Inclusions

scholarly journals Impaired TrkB Receptor Signaling Underlies Corticostriatal Dysfunction in Huntington’s Disease

Neuron ◽  
2014 ◽  
Vol 83 (1) ◽  
pp. 178-188 ◽  
Author(s):  
Joshua L. Plotkin ◽  
Michelle Day ◽  
Jayms D. Peterson ◽  
Zhong Xie ◽  
Geraldine J. Kress ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Receptor Signaling ◽  
Trkb Receptor

scholarly journals Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models

2015 ◽  
Vol 73 ◽  
pp. 388-398 ◽  
Author(s):  
Ulrike Träger ◽  
Ralph Andre ◽  
Anna Magnusson-Lind ◽  
James R.C. Miller ◽  
Colúm Connolly ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Cell Function ◽  
Immune Cell ◽  
Full Length ◽  
Immune Cell Function

scholarly journals A YAC Mouse Model for Huntington’s Disease with Full-Length Mutant Huntingtin, Cytoplasmic Toxicity, and Selective Striatal Neurodegeneration

Neuron ◽  
1999 ◽  
Vol 23 (1) ◽  
pp. 181-192 ◽  
Author(s):  
J.Graeme Hodgson ◽  
Nadia Agopyan ◽  
Claire-Anne Gutekunst ◽  
Blair R Leavitt ◽  
Fred LePiane ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Full Length ◽  
Mutant Huntingtin

scholarly journals Lack of mutant huntingtin in cortical efferents improves behavioral inflexibility and corticostriatal dynamics in Huntington’s disease mice

2019 ◽  
Vol 122 (6) ◽  
pp. 2621-2629
Author(s):  
Ana María Estrada-Sánchez ◽  
Courtney L. Blake ◽  
Scott J. Barton ◽  
Andrew G. Howe ◽  
George V. Rebec
Keyword(s):  
Motor Cortex ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Local Field ◽  
Local Field Potential ◽  
Primary Motor Cortex ◽  
Field Potential ◽  
Full Length ◽  
Mutant Huntingtin ◽  
Local Field Potential Lfp

Abnormal communication between cerebral cortex and striatum plays a major role in the motor symptoms of Huntington’s disease (HD), a neurodegenerative disorder caused by a mutation of the huntingtin gene ( mHTT). Because cortex is the main driver of striatal processing, we recorded local field potential (LFP) activity simultaneously in primary motor cortex (M1) and dorsal striatum (DS) in BACHD mice, a full-length HD gene model, and in a conditional BACHD/Emx-1 Cre (BE) model in which mHTT is suppressed in cortical efferents, while mice freely explored a plus-shaped maze beginning at 20 wk of age. Relative to wild-type (WT) controls, BACHD mice were just as active across >40 wk of testing but became progressively less likely to turn into a perpendicular arm as they approached the choice point of the maze, a sign of HD motor inflexibility. BE mice, in contrast, turned as freely as WT throughout testing. Although BE mice did not exactly match WT in LFP activity, the reduction in alpha (8–13 Hz), beta (13–30 Hz), and low-gamma (30–50 Hz) power that occurred in M1 of turning-impaired BACHD mice was reversed. No reversal occurred in DS. In fact, BE mice showed further reductions in DS theta (4–8 Hz), beta, and low-gamma power relative to the BACHD model. Coherence analysis indicated a dysregulation of corticostriatal information flow in both BACHD and BE mice. Collectively, our results suggest that mHTT in cortical outputs drives the dysregulation of select cortical frequencies that accompany the loss of behavioral flexibility in HD. NEW & NOTEWORTHY BACHD mice, a full-length genetic model of Huntington’s disease (HD), express aberrant local field potential (LFP) activity in primary motor cortex (M1) along with decreased probability of turning into a perpendicular arm of a plus-shaped maze, a motor inflexibility phenotype. Suppression of the mutant huntingtin gene in cortical output neurons prevents decline in turning and improves alpha, beta, and low-gamma activity in M1. Our results implicate cortical networks in the search for therapeutic strategies to alleviate HD motor signs.

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