Dysregulation of synaptic proteins, dendritic spine abnormalities and pathological plasticity of synapses as experience-dependent mediators of cognitive and psychiatric symptoms in Huntington’s disease

Neuroscience ◽  
2013 ◽  
Vol 251 ◽  
pp. 66-74 ◽  
Author(s):  
J. Nithianantharajah ◽  
A.J. Hannan
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Dendritic Spine ◽  
Psychiatric Symptoms ◽  
Synaptic Proteins ◽  
Spine Abnormalities

scholarly journals Management of Traumatic Ulcerations of Lips in a Case of Huntington’s Disease: A Novel Application of Essix Retainer

2021 ◽  
pp. 030157422110234
Author(s):  
Mohamed Iqbal J
Keyword(s):  
Quality Of Life ◽  
Characteristic Feature ◽  
Neurodegenerative Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Complete Resolution ◽  
Psychiatric Symptoms

Huntington’s disease is a progressive neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Dystonia of muscles is a characteristic feature of this condition. A case of Huntington’s disease, with orofacial dystonia, leading to severe uncontrolled biting of the lips, was referred by the Department of Neurology. Deep traumatic ulcerations were found in both upper and lower lips. A simple Essix retainer was fabricated and inserted, which acted as a barrier for the teeth from injuring the lips. The ulcers showed complete resolution in 3 to 4 weeks. The vacuum-formed retainers resulted in a good fit and resisted removal by the uncontrolled contortions of the orofacial muscles. The Essix retainer can be effectively used in improving the quality of life of patients, with Huntington’s disease, having such dystonia-related injuries to lips.

“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.

scholarly journals Disposition of Proteins and Lipids in Synaptic Membrane Compartments Is Altered in Q175/Q7 Huntington’s Disease Mouse Striatum

2021 ◽  
Vol 13 ◽  
Author(s):  
Maria Iuliano ◽  
Connor Seeley ◽  
Ellen Sapp ◽  
Erin L. Jones ◽  
Callie Martin ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Plasma Membranes ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Synaptic Membrane ◽  
Wild Type ◽  
Functional Changes ◽  
Mouse Striatum ◽  
Old Mice

Dysfunction at synapses is thought to be an early change contributing to cognitive, psychiatric and motor disturbances in Huntington’s disease (HD). In neurons, mutant Huntingtin collects in aggregates and distributes to the same sites as wild-type Huntingtin including on membranes and in synapses. In this study, we investigated the biochemical integrity of synapses in HD mouse striatum. We performed subcellular fractionation of striatal tissue from 2 and 6-month old knock-in Q175/Q7 HD and Q7/Q7 mice. Compared to striata of Q7/Q7 mice, proteins including GLUT3, Na+/K+ ATPase, NMDAR 2b, PSD95, and VGLUT1 had altered distribution in Q175/Q7 HD striata of 6-month old mice but not 2-month old mice. These proteins are found on plasma membranes and pre- and postsynaptic membranes supporting hypotheses that functional changes at synapses contribute to cognitive and behavioral symptoms of HD. Lipidomic analysis of mouse fractions indicated that compared to those of wild-type, fractions 1 and 2 of 6 months Q175/Q7 HD had altered levels of two species of PIP2, a phospholipid involved in synaptic signaling, increased levels of cholesterol ester and decreased cardiolipin species. At 2 months, increased levels of species of acylcarnitine, phosphatidic acid and sphingomyelin were measured. EM analysis showed that the contents of fractions 1 and 2 of Q7/Q7 and Q175/Q7 HD striata had a mix of isolated synaptic vesicles, vesicle filled axon terminals singly or in clusters, and ER and endosome-like membranes. However, those of Q175/Q7 striata contained significantly fewer and larger clumps of particles compared to those of Q7/Q7. Human HD postmortem putamen showed differences from control putamen in subcellular distribution of two proteins (Calnexin and GLUT3). Our biochemical, lipidomic and EM analysis show that the presence of the HD mutation conferred age dependent disruption of localization of synaptic proteins and lipids important for synaptic function. Our data demonstrate concrete biochemical changes suggesting altered integrity of synaptic compartments in HD mice that may mirror changes in HD patients and presage cognitive and psychiatric changes that occur in premanifest HD.

scholarly journals Therapeutic management of movement disorders present in Huntington’s Disease: a literature review

2021 ◽  
Author(s):  
Camila Angelo Vidal de Figueiredo ◽  
Kaline dos Santos Kishishita Castro ◽  
Sílvia Raimunda Costa Leite
Keyword(s):  
Quality Of Life ◽  
Literature Review ◽  
Adverse Effects ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Therapeutic Management ◽  
Abnormal Gait ◽  
Botulinum Toxin Injections

Background: Huntington’s Disease (HD) is a hereditary neurodegenerative genetic disease with motor, cognitive and behavioral repercussions that interferes in several areas of the patients’ lives. Therefore, to increase the quality of life for patients the therapeutic management of symptoms is necessary. Objective: to elucidate the main forms of treatment that reduces motor disorders present in HD. Methods: an integrative literature review was conducted using scientific articles published between 2016-2020 about this topic found in Pubmed and Google Scholar databases. Results: the chorea treatment in HD can be done using Tetrabenazine, deutetrabenazine or antipsychotics. During a study by the Huntington Study Group (HSG), tetrabenazine proved its efficacy, however, due to several adverse effects, its use was reduced. Thus, deutetrabenazine was created, which consists in a tetrabenazine deuterated version, with a longer half- life and less adverse effects. Studies by the HSG found that besides reducing chorea, it also improves motor function in general in patients. Antipsychotics are used when the patient has behavioral and psychiatric symptoms that prevent him from using the other drugs. The dystonia treatment involves physiotherapy and botulinum toxin injections, which are also used in the bruxism therapy, along with mouth protectors. Abnormal gait and balance problems can be reduced with psychomotor rehabilitation, physiotherapy, and using a walker. Conclusion: the control of HD motor symptoms is an important way to increase patients’ quality of life. Therefore, more studies are necessary to expand the effective therapeutic options.

scholarly journals Alterations in transcranial sonography among Huntington’s disease patients with psychiatric symptoms

2020 ◽  
Vol 127 (7) ◽  
pp. 1047-1055
Author(s):  
Grzegorz Witkowski ◽  
Katarzyna Jachinska ◽  
Iwona Stepniak ◽  
Karolina Ziora-Jakutowicz ◽  
Halina Sienkiewicz-Jarosz
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Transcranial Sonography

F57 Psychiatric symptoms in huntington’s disease: correlations between interview and self-report measures in the capit-hd2 beta-testing study

2018 ◽  
Author(s):  
Isobel McMillan ◽  
Duncan McLauchlan ◽  
Monica Busse ◽  
Anne-Catherine Bachoud-Lévi ◽  
Ralf Reilmann ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Self Report ◽  
Beta Testing

scholarly journals Abnormalities in the Motor Unit of a Fast-Twitch Lower Limb Skeletal Muscle in Huntington’s Disease

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141988621 ◽  
Author(s):  
Priscila Aparecida Costa Valadão ◽  
Bárbara Campos de Aragão ◽  
Jéssica Neves Andrade ◽  
Matheus Proença S. Magalhães-Gomes ◽  
Giselle Foureaux ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Tibialis Anterior ◽  
Neuromuscular Junctions ◽  
Motor Behavior ◽  
Psychiatric Symptoms ◽  
Artificial Chromosome ◽  
Ultrastructural Level ◽  
Fast Twitch

Huntington’s disease (HD) is a disorder characterized by chronic involuntary movements, dementia, and psychiatric symptoms. It is caused by a mutation in the gene that encodes for huntingtin protein (HTT), leading to the formation of mutant proteins expressed in various tissues. Although brain pathology has become the hallmark for HD, recent studies suggest that damage of peripheral structures also contributes to HD progression. We previously identified severe alterations in the motor units that innervate cervical muscles in 12-month-old BACHD (Bacterial Artificial Chromosome Huntington’s Disease) mice, a well-established mouse model for HD. Here, we studied lumbar motoneurons and their projections onto hind limb fast-twitch skeletal muscles (tibialis anterior), which control balance and gait in HD patients. We found that lumbar motoneurons were altered in the HD mouse model; the number and size of lumbar motoneurons were reduced in BACHD. Structural alterations were also present in the sciatic nerve and neuromuscular junctions. Acetylcholine receptors were organized in several small patches (acetylcholine receptor fragmentation), many of which were partially innervated. In BACHD mice, we observed atrophy of tibialis anterior muscles, decreased expression of glycolytic fast Type IIB fibers, and at the ultrastructural level, alterations of sarcomeres and mitochondria. Corroborating all these findings, BACHD animals performed worse on motor behavior tests. Our results provide additional evidences that nerve–muscle communication is impaired in HD and that motoneurons from distinct spinal cord locations are similarly affected in the disease.

scholarly journals Bioinformatic gene analysis for potential therapeutic targets of Huntington’s disease in pre-symptomatic and symptomatic stage

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Chunchen Xiang ◽  
Shengri Cong ◽  
Bin Liang ◽  
Shuyan Cong
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Differentially Expressed Genes ◽  
Bioinformatics Analysis ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Therapeutic Targets ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Transcriptional Dysregulation

Abstract Background Huntington’s disease (HD) is a neurodegenerative disorder characterized by psychiatric symptoms, serious motor and cognitive deficits. Certain pathological changes can already be observed in pre-symptomatic HD (pre-HD) patients; however, the underlying molecular pathogenesis is still uncertain and no effective treatments are available until now. Here, we reanalyzed HD-related differentially expressed genes from the GEO database between symptomatic HD patients, pre-HD individuals, and healthy controls using bioinformatics analysis, hoping to get more insight in the pathogenesis of both pre-HD and HD, and shed a light in the potential therapeutic targets of the disease. Methods Pre-HD and symptomatic HD differentially expressed genes (DEGs) were screened by bioinformatics analysis Gene Expression Omnibus (GEO) dataset GSE1751. A protein–protein interaction (PPI) network was used to select hub genes. Subsequently, Gene Ontology (GO) enrichment analysis of DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of hub genes were applied. Dataset GSE24250 was downloaded to verify our hub genes by the Kaplan–Meier method using Graphpad Prism 5.0. Finally, target miRNAs of intersected hub genes involved in pre-HD and symptomatic HD were predicted. Results A total of 37 and 985 DEGs were identified in pre-HD and symptomatic HD, respectively. The hub genes, SIRT1, SUZ12, and PSMC6, may be implicated in pre-HD, and the hub genes, FIS1, SIRT1, CCNH, SUZ12, and 10 others, may be implicated in symptomatic HD. The intersected hub genes, SIRT1 and SUZ12, and their predicted target miRNAs, in particular miR-22-3p and miR-19b, may be significantly associated with pre-HD. Conclusion The PSMC6, SIRT1, and SUZ12 genes and their related ubiquitin-mediated proteolysis, transcriptional dysregulation, and histone metabolism are significantly associated with pre-HD. FIS1, CCNH, and their related mitochondrial disruption and transcriptional dysregulation processes are related to symptomatic HD, which might shed a light on the elucidation of potential therapeutic targets in HD.

F56 Psychiatric symptoms in huntington’s disease: relationship to disease stage in the CAPIT-HD2 beta-testing study

2018 ◽  
Author(s):  
Isobel McMillan ◽  
Duncan McLauchlan ◽  
Monica Busse ◽  
Anne-Catherine Bachoud-Lévi ◽  
Ralf Reilmann ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Disease Stage ◽  
Beta Testing

Late-Onset Huntington's Disease: A Geriatric Psychiatry Perspective

1996 ◽  
Vol 9 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Kenneth I. Shulman ◽  
Anne Lennox ◽  
Harry Karlinsky
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Elderly Patients ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Late Onset ◽  
Clinical Aspects ◽  
Illustrative Case ◽  
Wide Range

Late-onset Huntington's disease is more common than has been generally appreciated and is associated with a wide range of psychiatric symptoms and syndromes. Geriatric psychiatrists have an important role to play in establishing the diagnosis and providing guidance to elderly patients and their families as they struggle with difficult management decisions. An illustrative case report and selective literature review are presented that highlight the genetic and clinical aspects of the condition.

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