Cognitive Impairments in Cerebellar Degeneration: A Comparison With Huntington’s Disease

2004 ◽  
Vol 16 (2) ◽  
pp. 176-184 ◽  
Author(s):  
Jason Brandt ◽  
Iracema Leroi ◽  
Elizabeth O’Hearn ◽  
Adam Rosenblatt ◽  
Russell L. Margolis
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Impairments ◽  
Cerebellar Degeneration

Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington's disease

2015 ◽  
Vol 82 ◽  
pp. 66-77 ◽  
Author(s):  
Supriya Swarnkar ◽  
Youjun Chen ◽  
William M. Pryor ◽  
Neelam Shahani ◽  
Damon T. Page ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Ectopic Expression ◽  
Cerebellar Degeneration

scholarly journals Do Changes in Synaptic Autophagy Underlie the Cognitive Impairments in Huntington’s Disease?

2021 ◽  
pp. 1-12
Author(s):  
Hilary Grosso Jasutkar ◽  
Ai Yamamoto
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Impairments ◽  
Critical Role ◽  
Pathological Changes ◽  
Cognitive Changes ◽  
Underlying Pathophysiology ◽  
Insight Into ◽  
Early Manifestation ◽  
Made In

Although Huntington’s disease (HD) is classically considered from the perspective of the motor syndrome, the cognitive changes in HD are prominent and often an early manifestation of disease. As such, investigating the underlying pathophysiology of cognitive changes may give insight into important and early neurodegenerative events. In this review, we first discuss evidence from both HD patients and animal models that cognitive changes correlate with early pathological changes at the synapse, an observation that is similarly made in other neurodegenerative conditions that primarily affect cognition. We then describe how autophagy plays a critical role supporting synaptic maintenance in the healthy brain, and how autophagy dysfunction in HD may thereby lead to impaired synaptic maintenance and thus early manifestations of disease.

scholarly journals Restoring GABAergic inhibition rescues memory deficits in a Huntington’s disease mouse model

2018 ◽  
Vol 115 (7) ◽  
pp. E1618-E1626 ◽  
Author(s):  
Zahra Dargaei ◽  
Jee Yoon Bang ◽  
Vivek Mahadevan ◽  
C. Sahara Khademullah ◽  
Simon Bedard ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Learning And Memory ◽  
Cognitive Impairments ◽  
Memory Deficits ◽  
Gabaergic Inhibition ◽  
Wild Type ◽  
Excitatory Action ◽  
Excitatory Gaba

Huntington’s disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role of inhibition in learning and memory, we hypothesized that aberrant KCC2 function contributes to the hippocampal-associated learning and memory deficits in HD. We discovered that Htt and KCC2 interact in the hippocampi of wild-type and R6/2-HD mice, with a decrease in KCC2 expression in the hippocampus of R6/2 and YAC128 mice. The reduced expression of the Cl−-extruding cotransporter KCC2 is accompanied by an increase in the Cl−-importing cotransporter NKCC1, which together result in excitatory GABA in the hippocampi of HD mice. NKCC1 inhibition by the FDA-approved NKCC1 inhibitor bumetanide abolished the excitatory action of GABA and rescued the performance of R6/2 mice on hippocampal-associated behavioral tests.

Cerebellar Degeneration Signature in Huntington’s Disease

2021 ◽  
Author(s):  
Gustavo Padron-Rivera ◽  
Rosalinda Diaz ◽  
Israel Vaca-Palomares ◽  
Adriana Ochoa ◽  
Carlos R. Hernandez-Castillo ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cerebellar Degeneration

scholarly journals Intact Ability to Learn Internal Models of Arm Dynamics in Huntington's Disease But Not Cerebellar Degeneration

2005 ◽  
Vol 93 (5) ◽  
pp. 2809-2821 ◽  
Author(s):  
Maurice A. Smith ◽  
Reza Shadmehr
Keyword(s):  
Huntington's Disease ◽  
Error Correction ◽  
Huntington’S Disease ◽  
Preceding Trial ◽  
Cerebellar Degeneration ◽  
Control Mechanisms ◽  
Compensatory Mechanisms ◽  
Motor Commands ◽  
Dependent Change ◽  
On Line

Two different compensatory mechanisms are engaged when the nervous system senses errors during a reaching movement. First, on-line feedback control mechanisms produce in-flight corrections to reduce errors in the on-going movement. Second, these errors modify the internal model with which the motor plan is transformed into motor commands for the subsequent movements. What are the neural mechanisms of these compensatory systems? In a previous study, we reported that while on-line error correction was disturbed in patients with Huntington's disease (HD), it was largely intact in patients with cerebellar degeneration. Here we altered dynamics of reaching and studied the effect of error in one trial on the motor commands that initiated the subsequent trial. We observed that in patients with cerebellar degeneration, motor commands changed from trial-to-trial by an amount that was comparable to control subjects. However, these changes were random and were uninformed by the error in the preceding trial. In contrast, the change in motor commands of HD patients was strongly related to the error in the preceding trial. This error-dependent change had a sensitivity that was comparable to healthy controls. As a result, HD patients exhibited no significant deficits in adapting to novel arm dynamics, whereas cerebellar subjects were profoundly impaired. These results demonstrate a double dissociation between on-line and trial-to-trial error correction suggesting that these compensatory mechanisms have distinct neural bases that can be differentially affected by disease.

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