scholarly journals Early dysfunction and progressive degeneration of the subthalamic nucleus in mouse models of Huntington's disease

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jeremy F Atherton ◽  
Eileen L McIver ◽  
Matthew RM Mullen ◽  
David L Wokosin ◽  
D James Surmeier ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Subthalamic Nucleus ◽  
Glutamate Uptake ◽  
Oxidant Stress ◽  
Katp Channels ◽  
Receptor Antagonism ◽  
Progressive Degeneration

The subthalamic nucleus (STN) is an element of cortico-basal ganglia-thalamo-cortical circuitry critical for action suppression. In Huntington's disease (HD) action suppression is impaired, resembling the effects of STN lesioning or inactivation. To explore this potential linkage, the STN was studied in BAC transgenic and Q175 knock-in mouse models of HD. At <2 and 6 months of age autonomous STN activity was impaired due to activation of KATP channels. STN neurons exhibited prolonged NMDA receptor-mediated synaptic currents, caused by a deficit in glutamate uptake, and elevated mitochondrial oxidant stress, which was ameliorated by NMDA receptor antagonism. STN activity was rescued by NMDA receptor antagonism or the break down of hydrogen peroxide. At 12 months of age approximately 30% of STN neurons had been lost, as in HD. Together, these data argue that dysfunction within the STN is an early feature of HD that may contribute to its expression and course.

scholarly journals Author response: Early dysfunction and progressive degeneration of the subthalamic nucleus in mouse models of Huntington's disease

2016 ◽  
Author(s):  
Jeremy F Atherton ◽  
Eileen L McIver ◽  
Matthew RM Mullen ◽  
David L Wokosin ◽  
D James Surmeier ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Subthalamic Nucleus ◽  
Author Response ◽  
Progressive Degeneration

scholarly journals Embryonic Mutant Huntingtin Aggregate Formation in Mouse Models of Huntington’s Disease

2016 ◽  
Vol 5 (4) ◽  
pp. 343-346 ◽  
Author(s):  
Alexander P. Osmand ◽  
Terry Jo. Bichell ◽  
Aaron B. Bowman ◽  
Gillian P. Bates
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Mutant Huntingtin ◽  
Aggregate Formation

scholarly journals The Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington’s Disease Mouse Models

Cell Reports ◽  
2012 ◽  
Vol 2 (6) ◽  
pp. 1492-1497 ◽  
Author(s):  
Vanita Chopra ◽  
Luisa Quinti ◽  
Jinho Kim ◽  
Lorraine Vollor ◽  
K. Lakshmi Narayanan ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models

scholarly journals Dysfunctions in circadian behavior and physiology in mouse models of Huntington's disease

2011 ◽  
Vol 228 (1) ◽  
pp. 80-90 ◽  
Author(s):  
Takashi Kudo ◽  
Analyne Schroeder ◽  
Dawn H. Loh ◽  
Dika Kuljis ◽  
Maria C. Jordan ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Circadian Behavior

scholarly journals Skeletal muscle regeneration is altered in the R6/2 mouse model of Huntington's disease

2022 ◽  
Author(s):  
Sanzana Hoque ◽  
Marie Sjogren ◽  
Valerie Allamand ◽  
Kinga Gawlik ◽  
Naomi Franke ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Muscle Damage ◽  
Satellite Cell ◽  
Mouse Models ◽  
Satellite Cells ◽  
Muscle Fibers ◽  
Cag Repeat ◽  
Skeletal Muscle Regeneration

Huntington's disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise. In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice. We found that, similar to R6/2 adult mice, neonatal R6/2 mice also exhibit a significant reduction in myofiber width and morphological changes in gastrocnemius and soleus muscles compared to WT mice. Cardiotoxin (CTX)-induced acute muscle damage in R6/2 and WT mice showed that the Pax7+ satellite cell pool was dampened in R6/2 mice at 4 weeks post-injection, and R6/2 mice exhibited an altered inflammatory profile in response to acute damage. Our results suggest that, in addition to the mutant HTT degenerative effects in mature muscle fibers, expression of mutant HTT in satellite cells might alter developmental and regenerative processes to contribute to the progressive muscle mass loss in HD. Taken together, the results presented here encourage further studies evaluating the underlying mechanisms of satellite cell dysfunction in HD mouse models.

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