scholarly journals In vivo characterization of white matter pathology in premanifest huntington's disease

2018 ◽  
Vol 84 (4) ◽  
pp. 497-504 ◽  
Author(s):  
Jiaying Zhang ◽  
Sarah Gregory ◽  
Rachael I. Scahill ◽  
Alexandra Durr ◽  
David L. Thomas ◽  
...  
Keyword(s):  
White Matter ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
White Matter Pathology ◽  
In Vivo Characterization

scholarly journals White matter changes in Huntington’s disease and the demyelination hypothesis: a critical review

2019 ◽  
Author(s):  
chiara casella ◽  
Claudia Metzler-Baddeley ◽  
Derek Jones ◽  
Ilona Lipp
Keyword(s):  
White Matter ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Biological Properties ◽  
Disease Pathogenesis ◽  
Tissue Modeling ◽  
Cortical Grey Matter ◽  
Neuroimaging Techniques

Huntington’s disease (HD) is a genetic neurodegenerative disorder, characterised by atrophy of the neostriatum, and cortical grey matter abnormalities. White matter (WM) alterations have recently been identified as a relevant pathophysiological feature of HD, but the etiology of WM degeneration, and its role in disease pathogenesis and progression remain unclear. An increasing body of research suggests that WM changes in HD are due to alterations in myelin-associated biological processes at the cellular and molecular level. This review first discusses evidence from neurochemical studies lending support to the ‘De-myelination hypothesis’ of HD, and pointing towards a role for aberrant myelination and changes in oligodendrocytes in HD WM. Next, evidence from neuroimaging studies is reviewed, the limitations of the described methodologies are discussed and suggested interpretations of findings from published studies are challenged. Although our understanding of HD-associated pathological changes in the brain will increasingly rely on neuroimaging techniques, the shortcomings of these methodologies must not be forgotten. Advances in MRI techniques and tissue modeling will enable a better characterization of the biological properties of WM microstructure, and will allow more specific monitoring of longitudinal changes noninvasively. This, in turn, will provide insight into disease pathogenesis and progression and facilitate the identification of disease-related biomarkers and the specification of outcome measures in clinical trials.

scholarly journals In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis

Brain ◽  
2017 ◽  
Vol 140 (11) ◽  
pp. 2912-2926 ◽  
Author(s):  
Tobias Granberg ◽  
Qiuyun Fan ◽  
Constantina Andrada Treaba ◽  
Russell Ouellette ◽  
Elena Herranz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
In Vivo Characterization

scholarly journals In Vivo Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease

2020 ◽  
Author(s):  
Ji Hea Yu ◽  
Bae-Geun Nam ◽  
MinGi Kim ◽  
Jung Hwa Seo ◽  
Sung-Rae Cho
Keyword(s):  
White Matter ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Grip Strength ◽  
Cell Fate ◽  
Gabaergic Neurons ◽  
Plastic State ◽  
Qrt Pcr ◽  
Virus Serotype

Abstract Background: White matter atrophy has been shown to precede the massive loss of striatal GABAergic neurons in Huntington’s disease (HD). The HD-induced white matter atrophy is associated with motor deficits. In vivo reprogramming toward a plastic state has emerged as a new approach for treating neurological diseases. Particularly, octamer-binding transcription factor 4 (OCT4) can induce myelin repair and functional recovery. This study investigated the effects of in situ expression of reprogramming factor OCT4 on behavioral performances, neural stem cell (NSC) niche activation in the subventricular zone (SVZ) and induction of cell fate specific to the changed microenvironment of HD. Methods: R6/2 mice, a transgenic mouse model of HD, randomly received adeno-associated virus serotype 9 (AAV9)-OCT4, AAV9-Null, or phosphate-buffered saline in both lateral ventricles at 4 weeks of age. To evaluate the behavioral improvement, rotarod test and grip strength test were performed at regular intervals. To investigate the expression of oligodendrocyte progenitor cell (OPC)-related genes, real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry were performed. Next, we assessed the amelioration of myelination deficits via transmission electron microscope (TEM) and magnetic resonance imaging (MRI) at 13 weeks of age. Finally, we confimed striatal neuroprotecion by qRT-PCR and confocal microscopy.Results: The AAV9-OCT4 group displayed significantly improved rotarod performance and grip strength compared to the control groups. Following AAV9-OCT4 treatment, the number of newly generated NSCs and OPCs was significantly increased in the SVZ, and the expression of OPC-related genes such as NG2, Olig2, PDGFRα, Wnt3 and myelin regulatory factor (MYRF), and glial cell-derived neuroprotective factor (GDNF) was significantly increased. Further, the amelioration of myelination deficits in the corpus callosum was observed through TEM and MRI, and striatal DARPP32+ GABAergic neurons significantly increased in the AAV9-OCT4 group.

scholarly journals In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy

Epilepsia ◽  
2011 ◽  
Vol 52 (4) ◽  
pp. 841-845 ◽  
Author(s):  
Pieter van Eijsden ◽  
Wim M. Otte ◽  
W. Saskia van der Hel ◽  
Onno van Nieuwenhuizen ◽  
Rick M. Dijkhuizen ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Status Epilepticus ◽  
White Matter ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
White Matter Pathology

scholarly journals Mutation-related apparent myelin, not axon density, drives white matter differences in premanifest Huntington's disease: Evidence from in vivo ultra-strong gradient MRI

2021 ◽  
Author(s):  
Chiara Casella ◽  
Maxime Chamberland ◽  
Pedro Luque-Laguna ◽  
Greg D Parker ◽  
Anne E Rosser ◽  
...  
Keyword(s):  
White Matter ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Volume Fraction ◽  
Diffusion Tensor ◽  
Direct Result ◽  
Magnetization Transfer Ratio ◽  
Axon Density ◽  
Strong Gradient

White matter (WM) alterations have been observed early in Huntington's disease (HD) progression but their role in the disease-pathophysiology remains unknown. We exploited ultra-strong-gradient MRI to tease apart contributions of myelin (with the magnetization transfer ratio), and axon density (with the restricted volume fraction from the Composite Hindered and Restricted Model of Diffusion) to WM differences between premanifest HD patients and age- and sex-matched controls. Diffusion tensor MRI (DT-MRI) measures were also assessed. We used tractometry to investigate region-specific changes across callosal segments with well-characterized early- and late-myelinating axonal populations, while brain-wise alterations were explored with tract-based cluster analysis (TBCA). Behavioural measures were included to explore disease-associated brain-function relationships. We detected lower myelin in the rostrum of patients (tractometry: p = 0.0343; TBCA: p = 0.030), but higher myelin in their splenium (p = 0.016). Importantly, patients' myelin and mutation size were positively associated (all p-values < 0.01), indicating that increased myelination might be a direct result of the mutation. Finally, myelin was higher than controls in younger patients but lower in older patients (p = 0.003), suggesting detrimental effects of increased myelination later in the course of the disease. Higher FR in patients' left cortico-spinal tract (CST) (p = 0.03) was detected, and was found to be positively associated with MTR in the posterior callosum (p = 0.033), possibly suggesting compensation to myelin alterations. This comprehensive, ultra-strong gradient MRI investigation provides novel evidence of CAG-driven myelin alterations in premanifest HD which may reflect neurodevelopmental, rather than neurodegenerative disease-associated changes.

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
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