Quantification of the Light Subunit of Neurofilament Protein in Cerebrospinal Fluid of Huntington ’s Disease Patients
We examined the relationships (Pearson correlations) between NFL-CSF levels and demographic (age, gender) and clinical (CAG repeat number, disease burden, UHDRS motor, behavioural, functional total scores and NPI scale) variables. All the participants gave their signed consent for the procedure.
Results
Demographic, clinical data and NFL-CSF levels of all participants are shown in Table 1. NFL-CSF results were significantly higher in all HD subjects [5014.4 (1557.3) ng/l] as compared to controls [331.4 (200.2) ng/l] (p<0.00) and were correlated with age (correlation coefficient -0.37, p<0.01) and CAG triplet number ...
Source: PLOS Currents Huntington Disease - August 31, 2018 Category: Neurology Authors: Natalia Szejko Source Type: research
Removal of the Mitochondrial Fission Factor Mff Exacerbates Neuronal Loss and Neurological Phenotypes in a Huntington ’ s Disease Mouse Model
CONCLUSIONS
Although inhibition of mitochondrial fission has been proposed as a therapeutic approach for HD, we find that removal of Mff, a mitochondrial fission factor, exacerbates the neurological phenotypes of HDR6/2 mice.Therefore, our results indicate that a deeper understanding of mitochondrial dynamics in HD is required before mitochondrial fission can be considered a therapeutic avenue for HD.
Data Availability Statement
The raw data for graphs in Figures 1-5 are available at https://figshare.com/s/584ca97ed838e5de3bde, with DOI: 10.6084/m9.figshare.6052007.
Competing Interests Statement
The authors have declared...
Source: PLOS Currents Huntington Disease - July 26, 2018 Category: Neurology Authors: dchan Source Type: research
[HD-17-0002R1] Removal of the Mitochondrial Fission Factor Mff Exacerbates Neuronal Loss and Neurological Phenotypes in a Huntington ’ s Disease Mouse Model
CONCLUSIONS
Although inhibition of mitochondrial fission has been proposed as a therapeutic approach for HD, we find that removal of Mff, a mitochondrial fission factor, exacerbates the neurological phenotypes of HDR6/2 mice.Therefore, our results indicate that a deeper understanding of mitochondrial dynamics in HD is required before mitochondrial fission can be considered a therapeutic avenue for HD.
Data Availability Statement
The raw data for graphs in Figures 1-5 are available at https://figshare.com/s/584ca97ed838e5de3bde, with DOI: 10.6084/m9.figshare.6052007.
Competing Interests Statement
The authors have declared...
Source: PLOS Currents Huntington Disease - March 30, 2018 Category: Neurology Authors: dchan Source Type: research
Correction: Effects of the Pimelic Diphenylamide Histone Deacetylase Inhibitor HDACi 4b on the R6/2 and N171-82Q Mouse Models of Huntington ’s Disease
Correction
There is an error in the second author’s name. The correct name is Elizabeth A. Wang. The correct citation is Chen JY, Wang EA, Galvan L, Huynh M, Joshi P, Cepeda C, Levine MS. Effects of the Pimelic Diphenylamide Histone Deacetylase Inhibitor HDACi 4b on the R6/2 and N171-82Q Mouse Models of Huntington’s Disease. PLOS Currents Huntington Disease. 2013 Feb 5 . Edition 1. doi: 10.1371/currents.hd.ec3547da1c2a520ba959ee7bf8bdd202.
Reference
Chen JY, Wang E, Galvan L, Huynh M, Joshi P, Cepeda C, Levine MS. Effects of the Pimelic Diphenylamide Histone Deacetylase Inhibitor HDACi 4b on the R6/2 and N171-82Q Mous...
Source: PLOS Currents Huntington Disease - July 11, 2017 Category: Neurology Authors: ploscurrents Source Type: research
Correction: Differential Synaptic and Extrasynaptic Glutamate-Receptor Alterations in Striatal Medium-Sized Spiny Neurons of Aged YAC128 Huntington ’ s Disease Mice
Correction
There is an error in the second author’s name. The correct name is Elizabeth A. Wang. The correct citation is Botelho EP, Wang EA, Chen JY, Holley S, Andre V, Cepeda C, Levine MS. Differential Synaptic and Extrasynaptic Glutamate-Receptor Alterations in Striatal Medium-Sized Spiny Neurons of Aged YAC128 Huntington’s Disease Mice. PLOS Currents Huntington Disease. 2014 May 21 . Edition 1. doi: 10.1371/currents.hd.34957c4f8bd7cb1f5ec47381dfc811c3.
Reference
Botelho EP, Wang E, Chen JY, Holley S, Andre V, Cepeda C, Levine MS. Differential Synaptic and Extrasynaptic Glutamate-Receptor Alterations in Striata...
Source: PLOS Currents Huntington Disease - July 11, 2017 Category: Neurology Authors: ploscurrents Source Type: research
Social Cognition, Executive Functions and Self-Report of Psychological Distress in Huntington ’s Disease
Conclusions
We found significant associations between self-report of psychological distress and performances on social cognitive tests but not on tests of executive functions. According to our findings HD patients that feel less psychologically distressed themselves perform worse on tests of the ability to recognize emotions, ToM and sarcasm in others. This is an interesting finding that may be of importance for understanding the interpersonal problems often associated with HD. We speculate that one mechanism for this finding may be that shared representations of self and other as well as insight and apathy may be closely ...
Source: PLOS Currents Huntington Disease - December 28, 2016 Category: Neurology Authors: idaunmack Source Type: research
Quality of Life of Cypriot Patients Suffering with Huntington ’s Disease
Conclusions
The study assessed, for the first time, the QoL of HD patients in Cyprus and demonstrated that QoL in the Cypriot HD patient population was moderately to severely affected by the disease. The disease was most frequently found to affect the ability of Cypriot patients to carry out their usual, day-to-day activities and to care for themselves. The psychological state was found to play a crucial role in the QoL of HD patients, since the majority of the patients, including pre-symptomatic ones, reported moderate anxiety and depression. In terms of the physical domain, a large number of HD patients reported moderate...
Source: PLOS Currents Huntington Disease - October 25, 2016 Category: Neurology Authors: elenivar at cytanet.com.cy Source Type: research
Effects of Anthocyanins on CAG Repeat Instability and Behaviour in Huntington ’s Disease R6/1 Mice
Conclusion
In conclusion, the instability index was reduced in the ear and the cortex of anthocyanin-treated compared to untreated R6/1 mice. The time spent in the centre square zone during the first five minutes of the open field test was neither significantly different between anthocyanin-treated and untreated R6/1 HD mice, nor between R6/1 HD and R6/1 WT mice. These results indicate no effects on anxiety-like behaviour. During the open field time course of 45 minutes R6/1 HD mice appeared to have cognitive deficits. Anthocyanin treatment may improve this deficit in R6/1 HD mice, although further studies are required...
Source: PLOS Currents Huntington Disease - July 5, 2016 Category: Neurology Authors: Linda Møllersen Source Type: research
Effects of Anthocyanins on CAG Repeat Instability and Behaviour in Huntington’s Disease R6/1 Mice
Conclusion
In conclusion, the instability index was reduced in the ear and the cortex of anthocyanin-treated compared to untreated R6/1 mice. The time spent in the centre square zone during the first five minutes of the open field test was neither significantly different between anthocyanin-treated and untreated R6/1 HD mice, nor between R6/1 HD and R6/1 WT mice. These results indicate no effects on anxiety-like behaviour. During the open field time course of 45 minutes R6/1 HD mice appeared to have cognitive deficits. Anthocyanin treatment may improve this deficit in R6/1 HD mice, although further studies are required...
Source: PLOS Currents Huntington Disease - July 5, 2016 Category: Neurology Authors: Linda Møllersen Source Type: research
Is There an Association of Physical Activity with Brain Volume, Behavior, and Day-to-day Functioning? A Cross Sectional Design in Prodromal and Early Huntington Disease
Conclusion
Interventions that could delay the onset of an HD motor diagnosis, particularly at a time when people are at their peak earning potential and raising families, may improve functioning and health-related quality of life. Interventions should begin prior to motor diagnosis because there is some evidence that much of the damage the disease causes is done by the time of diagnosis16,74,75. More specific recommendations require prospective, randomized controlled trials of physical activity interventions. There is evidence that metabolic and physiological responses to exercise are altered in HD76 and that intensive exe...
Source: PLOS Currents Huntington Disease - March 17, 2016 Category: Neurology Authors: McKenzie Wallace Source Type: research
Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance
Discussion
Using 36 months of data from early HD participants in TRACK-HD, we have studied associations between neuroleptics, SSRIs and SNRIs and performance on motor, cognitive and neuropsychiatric assessments. Our aim was to investigate whether therapies that are widely used in the symptomatic management of HD were likely to have concomitant effects not only on the symptom for which they were prescribed, but also for other endpoints. We adopted a statistical approach making use of the longitudinal nature of the data, using up to date methods and thinking on causality, accounting for prior medication use, use of other med...
Source: PLOS Currents Huntington Disease - January 11, 2016 Category: Neurology Authors: Ruth Keogh Source Type: research
Correction: Thiol-disulfide Oxidoreductases TRX1 and TMX3 Decrease Neuronal Atrophy in a Lentiviral Mouse Model of Huntington’s Disease
Correction
The author order is incorrect. The correct order of the authors is: Lu Z, Barrows L, Fox J.
Reference
Fox J, Lu Z, Barrows L. Thiol-disulfide Oxidoreductases TRX1 and TMX3 Decrease Neuronal Atrophy in a Lentiviral Mouse Model of Huntington’s Disease. PLOS Currents Huntington Disease. 2015 Nov 6 . Edition 1. doi: 10.1371/currents.hd.b966ec2eca8e2d89d2bb4d020be4351e. (Source: PLOS Currents Huntington Disease)
Source: PLOS Currents Huntington Disease - January 7, 2016 Category: Neurology Authors: ploscurrents Source Type: research
Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington ’s Disease
DISCUSSION
The involvement of mitochondrial defects in the molecular aetiology of HD was suggested for the first time more than ten years ago, based on the evidence that 3-NPA, an inhibitor of complex II of the respiratory chain, was per se able to induce Htt-like symptoms14,45,46. A number of reports have then described defects in the morphology of mitochondria in HD model cells15,19,47,48,49. Impaired respiratory chain activity50,51 and abnormalities of mitochondrial Ca2+ handling have been described in most of the experimental HD models currently in use9,41,52, reinforcing the idea of a role for mitochondrial defects an...
Source: PLOS Currents Huntington Disease - January 6, 2016 Category: Neurology Authors: Agnese De Mario Source Type: research
Calcium Handling by Endoplasmic Reticulum and Mitochondria in a Cell Model of Huntington’s Disease
DISCUSSION
The involvement of mitochondrial defects in the molecular aetiology of HD was suggested for the first time more than ten years ago, based on the evidence that 3-NPA, an inhibitor of complex II of the respiratory chain, was per se able to induce Htt-like symptoms14,45,46. A number of reports have then described defects in the morphology of mitochondria in HD model cells15,19,47,48,49. Impaired respiratory chain activity50,51 and abnormalities of mitochondrial Ca2+ handling have been described in most of the experimental HD models currently in use9,41,52, reinforcing the idea of a role for mitochondrial defects an...
Source: PLOS Currents Huntington Disease - January 6, 2016 Category: Neurology Authors: Agnese De Mario Source Type: research
Thiol-disulfide Oxidoreductases TRX1 and TMX3 Decrease Neuronal Atrophy in a Lentiviral Mouse Model of Huntington’s Disease
Discussion
Abnormal redox homeostasis and oxidative stress are consistent features of human HD and cell-based and animal models45,46. Identification of appropriate targets for modulation of redox homeostasis could provide novel therapeutic approaches for treating HD. Protein thiols are an important site of post-translational modification involved in the regulation of redox responsive cell signaling processes24. Oxidative stress can result in increased protein thiol oxidation and disruption of these homeostatic processes, potentially contributing to cell dysfunction and degeneration. Transgenic mice expressing the N171 mHTT...
Source: PLOS Currents Huntington Disease - November 6, 2015 Category: Neurology Authors: jfox7 at uwyo.edu Source Type: research
