Local and Global Abnormalities in Pre-symptomatic Huntington’s Disease Revealed by 7T Resting-state Functional MRI

Xie, Juan‐Juan; Li, Xiaoyan; Dong, Yi; Chen, Cong; Qu, Bo; Wang, Shuang; Han, Xu; Roe, Anna Wang; Lai, Hsin-Yi; Wu, Zhi‐Ying

doi:10.1007/s12264-022-00943-5

Cited by 6 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although structural studies of HD have generally found that striatum atrophy is a hallmark of HD patients even in the early stage and functional abnormalities have been considered sensible compared to structural atrophy, the current study only showed moderately decreased brain activity in the left striatum. This is consistent with most of the previous functional neuroimaging studies ( 27 ), supporting that the structural atrophy of the striatum did not represent the functional downregulation, and a dissociation pattern of structural and functional alterations exists. This might be partially explained by the neural compensation theory ( 26 ).…”

Section: Discussionsupporting

confidence: 92%

Aberrant resting-state brain activity in Huntington's disease: A voxel-based meta-analysis

et al. 2023

View full text Add to dashboard Cite

IntroductionFunctional neuroimaging could provide abundant information of underling pathophysiological mechanisms of the clinical triad including motor, cognitive and psychiatric impairment in Huntington's Disease (HD).MethodsWe performed a voxel-based meta-analysis using anisotropic effect size-signed differential mapping (AES-SDM) method.Results6 studies (78 symptomatic HD, 102 premanifest HD and 131 healthy controls) were included in total. Altered resting-state brain activity was primarily detected in the bilateral medial part of superior frontal gyrus, bilateral anterior cingulate/paracingulate gyrus, left insula, left striatum, right cortico-spinal projections area, right inferior temporal gyrus area, right thalamus, right cerebellum and right gyrus rectus area. Premanifest and symptomatic HD patients showed different alterative pattern in the subgroup analyses.DiscussionThe robust and consistent abnormalities in the specific brain regions identified in the current study could help to understand the pathophysiology of HD and explore reliable neuroimaging biomarkers for monitoring disease progression, or even predicting the onset of premanifest HD patients.

show abstract

Section: Discussionsupporting

confidence: 92%

Aberrant resting-state brain activity in Huntington's disease: A voxel-based meta-analysis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In previous studies, 3T MRI was used to examine the structural and functional alteration in PKD. These days, a stronger field 7T MRI with higher resolution and signal-to-noise may be more sensitive to detect functional alterations and can be applied in the following research [ 57 ]. In general, according to the findings in neuroimaging studies, abnormalities in the basal ganglia-thalamo-cortical circuit in PKD have been suspected for a long time.…”

Section: Pathophysiologic Mechanismsmentioning

confidence: 99%

Paroxysmal Kinesigenic Dyskinesia: Genetics and Pathophysiological Mechanisms

Xu,

Li,

2023

Neurosci. Bull.

Self Cite

View full text Add to dashboard Cite

Paroxysmal kinesigenic dyskinesia (PKD), the most common type of paroxysmal movement disorder, is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements. PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene. The exact pathophysiological mechanisms of PKD remain unclear, although the function of PRRT2 protein has been well characterized in the last decade. Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2, PKD may be channelopathy or synaptopathy, or both. In addition, the cerebellum is regarded as the key pathogenic area. Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes. Whereas, in PKD, other than the cerebellum, the role of the cerebrum including the cortex and thalamus needs to be further investigated.

show abstract

“…HD is characterized by preferential neuronal loss in the striatum [4]. As the disease progresses, degeneration also occurs in other brain regions, whereas the cerebellum is less affected [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington’s disease mice

Chen,

Qin,

Guo

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Huntington’s disease (HD) is a monogenic neurodegenerative disease, caused by the CAG trinucleotide repeat expansion in exon 1 of the Huntingtin (HTT) gene. The HTT gene encodes a large protein known to interact with many proteins. Huntingtin-associated protein 40 (HAP40) is one that shows high binding affinity with HTT and functions to maintain HTT conformation in vitro. However, the potential role of HAP40 in HD pathogenesis remains unknown. In this study, we found that the expression level of HAP40 is in parallel with HTT but inversely correlates with mutant HTT aggregates in mouse brains. Depletion of endogenous HAP40 in the striatum of HD140Q knock-in (KI) mice leads to enhanced mutant HTT aggregation and neuronal loss. Consistently, overexpression of HAP40 in the striatum of HD140Q KI mice reduced mutant HTT aggregation and ameliorated the behavioral deficits. Mechanistically, HAP40 preferentially binds to mutant HTT and promotes Lysine 48-linked ubiquitination of mutant HTT. Our results revealed that HAP40 is an important regulator of HTT protein homeostasis in vivo and hinted at HAP40 as a therapeutic target in HD treatment.

show abstract

Local and Global Abnormalities in Pre-symptomatic Huntington’s Disease Revealed by 7T Resting-state Functional MRI

Cited by 6 publications

References 15 publications

Aberrant resting-state brain activity in Huntington's disease: A voxel-based meta-analysis

Aberrant resting-state brain activity in Huntington's disease: A voxel-based meta-analysis

Paroxysmal Kinesigenic Dyskinesia: Genetics and Pathophysiological Mechanisms

HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington’s disease mice

Contact Info

Product

Resources

About