Plasma Cytokine Levels in Relation to Neuropsychiatric Symptoms and Cognitive Dysfunction in Huntington’s disease

2016 ◽  
Vol 5 (4) ◽  
pp. 369-377 ◽  
Author(s):  
Jos A. Bouwens ◽  
Erik van Duijn ◽  
Christa M. Cobbaert ◽  
Raymund A.C. Roos ◽  
Roos C. van der Mast ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Dysfunction ◽  
Neuropsychiatric Symptoms ◽  
Plasma Cytokine ◽  
Cytokine Levels

scholarly journals Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

2021 ◽  
Author(s):  
Danielle A. Simmons ◽  
Brian D. Mills ◽  
Robert R. Butler III ◽  
Jason Kuan ◽  
Tyne L. M. McHugh ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Treatment Response ◽  
Diffusion Tensor ◽  
Disease Onset ◽  
Therapeutic Effects ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Pharmacodynamic Biomarkers

AbstractHuntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

“organic Personality Disorder” as Part of Early Neuropsychiatric Manifestations in Huntington’s Disease - a Case Report

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Maia
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Age Of Onset ◽  
Neuropsychiatric Symptoms ◽  
Personality Change ◽  
Psychotic Symptoms ◽  
Autosomal Dominant Disorder ◽  
Neuropsychiatric Manifestations ◽  
Psychiatric Manifestations

Huntington's Disease (HD) is an inherited autosomal dominant disorder characterized by motor, cognitive and psychiatric symptomatology, being considered a paradigmatic neuropsychiatric disorder that includes all three components of the "Triadic Syndromes": dyskinesia, dementia and depression.Firstly described in 1872 as an "Hereditary Chorea" by George Huntington only in 1993 was its responsible gene identified. A person who inherits the HD gene will sooner or later develop the disease. the age of onset, early signs and rate of disease progression vary greatly from person to person.Neuropsychiatric symptoms are an integral part of HD and have been considered the earliest markers of the disease, presenting sometimes more than 10 years before a formal diagnosis is done. Patients may experience dysphoria, mood swings, agitation, irritability, hostile outbursts, psychotic symptoms and deep bouts of depression with suicidal ideation. Personality change is reported in 48% of the cases, with the paranoid subtype being described as the most prevalent. the clinical case presented illustrates a case of HD which started with insidious psychiatric symptoms and an important personality change.Despite a wide number of medications being prescribed to help control emotional, movement and behaviour problems, there is still no treatment to stop or reverse the course of the disease. Furthermore, psychiatric manifestations are often amenable to treatment, and relief of these symptoms may provide significant improvement in patient's and caregivers quality of life.A greater awarness of psychiatric manifestations of HD is essential to an earlier diagnosis and an optimized therapeutic approach.

G04 Screening For Cognitive Dysfunction In Huntington's Disease With The Clock Drawing Test

2014 ◽  
Vol 85 (Suppl 1) ◽  
pp. A51-A51
Author(s):  
P. Terwindt ◽  
A. Hubers ◽  
E. Giltay ◽  
R. van der Mast ◽  
E. van Duijn
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Dysfunction ◽  
Clock Drawing Test ◽  
Clock Drawing ◽  
Drawing Test

H05 Prevalence And Correlates Of Neuropsychiatric Symptoms In Pre-manifested And Early Stage Huntington's Disease

2014 ◽  
Vol 85 (Suppl 1) ◽  
pp. A53-A53
Author(s):  
S. Martinez-Horta ◽  
J. Perez-Perez ◽  
M. Carceller ◽  
R. de Bobadilla ◽  
J. Pagonabarraga ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Early Stage ◽  
Neuropsychiatric Symptoms

Functional Brain Correlates of Neuropsychiatric Symptoms in Presymptomatic Huntington’s Disease: The IMAGE-HD Study

2015 ◽  
Vol 4 (4) ◽  
pp. 325-332 ◽  
Author(s):  
Govinda R. Poudel ◽  
Shannon Driscoll ◽  
Juan F. Domínguez D ◽  
Julie C. Stout ◽  
Andrew Churchyard ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuropsychiatric Symptoms ◽  
Functional Brain ◽  
Brain Correlates

scholarly journals Corrigendum to “Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's disease” [Parkinsonism Relat. Disord. 25C (2016) 58–64]

2016 ◽  
Vol 31 ◽  
pp. 161 ◽  
Author(s):  
Saul Martinez-Horta ◽  
Jesus Perez-Perez ◽  
Erik van Duijn ◽  
Ramon Fernandez-Bobadilla ◽  
Mar Carceller ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Early Stage ◽  
Neuropsychiatric Symptoms

scholarly journals Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Cristine de Paula Nascimento-Castro ◽  
Ana Claudia Wink ◽  
Victor Silva da Fônseca ◽  
Claudia Daniele Bianco ◽  
Elisa C. Winkelmann-Duarte ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuronal Differentiation ◽  
Neurodegenerative Disorder ◽  
Neuropsychiatric Symptoms ◽  
Chronic Administration ◽  
Nuclear Antigen ◽  
Ki 67 ◽  
Affective Symptoms

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in the HD gene, resulting in an extended polyglutamine tract in the protein huntingtin. HD is traditionally viewed as a movement disorder, but cognitive and neuropsychiatric symptoms also contribute to the clinical presentation. Depression is one of the most common psychiatric disturbances in HD, present even before manifestation of motor symptoms. Diagnosis and treatment of depression in HD-affected individuals are essential aspects of clinical management in this population, especially owing to the high risk of suicide. This study investigated whether chronic administration of the antioxidant probucol improved motor and affective symptoms as well as hippocampal neurogenic function in the YAC128 transgenic mouse model of HD during the early- to mild-symptomatic stages of disease progression. The motor performance and affective symptoms were monitored using well-validated behavioral tests in YAC128 mice and age-matched wild-type littermates at 2, 4, and 6 months of age, after 1, 3, or 5 months of treatment with probucol (30 mg/kg/day via water supplementation, starting on postnatal day 30). Endogenous markers were used to assess the effect of probucol on cell proliferation (Ki-67 and proliferation cell nuclear antigen (PCNA)) and neuronal differentiation (doublecortin (DCX)) in the hippocampal dentate gyrus (DG). Chronic treatment with probucol reduced the occurrence of depressive-like behaviors in early- and mild-symptomatic YAC128 mice. Functional improvements were not accompanied by increased progenitor cell proliferation and neuronal differentiation. Our findings provide evidence that administration of probucol may be of clinical benefit in the management of early- to mild-symptomatic HD.

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