- : Auditory dysfunction in patients with Huntington's disease. - pubmed: huntington's or hunt...
Auditory dysfunction in patients with Huntington's disease.
Clin Neurophysiol. 2017 Jul 29;128(10):1946-1953
Authors: Profant O, Roth J, Bureš Z, Balogová Z, Lišková I, Betka J, Syka J
OBJECTIVE: Huntington's disease (HD) is an autosomal, dominantly inherited, neurodegenerative disease. The main clinical features are motor impairment, progressive cognitive deterioration and behavioral changes. The aim of our study was to find out whether patients with HD suffer from disorders of the auditory system.
METHODS: A group of 17 genetically verified patients (11 males, 6 females) with various stages of HD (examined by UHDRS - motor part and total functional capacity, MMSE for cognitive functions) underwent an audiological examination (high frequency pure tone audiometry, otoacoustic emissions, speech audiometry, speech audiometry in babble noise, auditory brainstem responses). Additionally, 5 patients underwent a more extensive audiological examination, focused on central auditory processing. The results were compared with a group of age-matched healthy volunteers.
RESULTS: Our results show that HD patients have physiologic hearing thresholds, otoacoustic emissions and auditory brainstem responses; however, they display a significant decrease in speech understanding, especially under demanding conditions (speech in noise) compared to age-matched controls. Additional auditory tests also show deficits in sound source localization, based on temporal and intensity cues. We also observed a statistically significant correlation between the perception of speech in noise, and motoric and cognitive functions. However, a correlation between genetic predisposition (number of triplets) and function of inner ear was not found.
CONCLUSIONS: We conclude that HD negatively influences the function of the central part of the auditory system at cortical and subcortical levels, altering predominantly speech processing and sound source lateralization.
SIGNIFICANCE: We have thoroughly characterized auditory pathology in patients with HD that suggests involvement of central auditory and cognitive areas.
PMID: 28826025 [PubMed - as supplied by publisher]
- : Walking-Related Dual-Task Interference in Early-to-Middle-Stage Huntington's Disease: An Auditory Event Related Potential Study. - pubmed: huntington's or hunt...
Walking-Related Dual-Task Interference in Early-to-Middle-Stage Huntington's Disease: An Auditory Event Related Potential Study.
Front Psychol. 2017;8:1292
Authors: de Tommaso M, Ricci K, Montemurno A, Vecchio E, Invitto S
Objective: To compare interference between walking and a simple P3 auditory odd-ball paradigm in patients with Huntington's disease (HD) and age- and sex-matched controls. Methods: Twenty-four early-to-middle-stage HD patients and 14 age- and sex-matched healthy volunteers were examined. EEG-EMG recordings were obtained from 21 scalp electrodes and eight bipolar derivations from the legs. Principal component analysis was used to obtain artifact-free recordings. The stimulation paradigm consisted of 50 rare and 150 frequent stimuli and was performed in two conditions: standing and walking along a 10 by 5 m path. P3 wave amplitude and latency and EEG and EMG spectral values were compared by group and experimental condition and correlated with clinical features of HD. Results: P3 amplitude increased during walking in both HD patients and controls. This effect was inversely correlated with motor impairment in HD patients, who showed a beta-band power increase over the parieto-occipital regions in the walking condition during the P3 task. Walking speed and counting of rare stimuli were not compromised by concurrence of motor and cognitive demands. Conclusion: Our results showed that walking increased P3 amplitude in an auditory task, in both HD patients and controls. Concurrent cognitive and motor stimulation could be used for rehabilitative purposes as a means of enhancing activation of cortical compensatory reserves, counteracting potential negative interference and promoting the integration of neuronal circuits serving different functions.
PMID: 28824485 [PubMed]
- : Selective Sparing of Striatal Interneurons after Poly (ADP-Ribose) Polymerase 1 Inhibition in the R6/2 Mouse Model of Huntington's Disease. - pubmed: huntington's or hunt...
Selective Sparing of Striatal Interneurons after Poly (ADP-Ribose) Polymerase 1 Inhibition in the R6/2 Mouse Model of Huntington's Disease.
Front Neuroanat. 2017;11:61
Authors: Paldino E, Cardinale A, D'Angelo V, Sauve I, Giampà C, Fusco FR
Poly (ADP-ribose) polymerases (PARPs) are enzymes that catalyze ADP-ribose units transfer from NAD to their substrate proteins. It has been observed that PARP-1 is able to increase both post-ischemic and excitotoxic neuronal death. In fact, we have previously shown that, INO-1001, a PARP-1 inhibitor, displays a neuroprotective effect in the R6/2 model of Huntington's disease (HD). In this study, we investigated the effects of PARP-1-inhibition on modulation of phosphorylated c-AMP response element binding protein (pCREB) and CREB-binding protein (CBP) localization in the different striatal neuronal subsets. Moreover, we studied the neurodegeneration of those interneurons that are particularly vulnerable to HD such as parvalbuminergic and calretininergic, and of other subclasses of interneurons that are known to be resistant, such as cholinergic and somatostatinergic interneurons. Transgenic mice were treated with INO-1001 (10 mg/Kg daily) starting from 4 weeks of age. Double-label immunofluorescence was performed to value the distribution of CBP in ubiquitinated Neuronal intranuclear inclusions (NIIs) in the striatum. INO-1001-treated and saline-treated brain sections were incubated with: goat anti-choline acetyl transferase; goat anti-nitric oxide synthase; mouse anti-parvalbumin and mouse anti-calretinin. Morphometric evaluation and cell counts were performed. Our study showed that the PARP inhibitor has a positive effect in sparing parvalbumin and calretinin-containing interneurons of the striatum, where CREB was upregulated. Moreover, INO-1001 promoted CBP localization into the nuclei of the R6/2 mouse. The sum of our data corroborates the previous observations indicating PARP inhibition as a possible therapeutic tool to fight HD.
PMID: 28824383 [PubMed]
- : Beneficial effects of glatiramer acetate in Huntington's disease mouse models: evidence for BDNF-elevating and immunomodulatory mechanisms. - pubmed: huntington's or hunt...
Beneficial effects of glatiramer acetate in Huntington's disease mouse models: evidence for BDNF-elevating and immunomodulatory mechanisms.
Brain Res. 2017 Aug 17;:
Authors: Corey-Bloom J, Aikin AM, Gutierrez A, Salam J, Howell T, Thomas EA
Huntington's disease (HD) is a fatal, neurodegenerative movement disorder that has no cure and few treatment options. In these preclinical studies, we tested the effects of chronic treatment of glatiramer acetate (GA; Copaxone®), an FDA-approved drug used as first-line therapy for MS, in two different HD mouse models, and explored potential mechanisms of action of drug efficacy. Groups of CAG140 knock-in and N171-82Q transgenic mice were treated with GA for up to 1 year of age (CAG140 knock-in mice) or 20 weeks (N171-82Q mice). Various behavioral assays were measured over the course of drug treatment whereby GA treatment delayed the onset and reduced the severity of HD behavioral symptoms in both mouse models. The beneficial actions of GA were associated with elevated levels of promoter I- and IV-driven brain-derived neurotrophic factor (Bdnf) expression and reduced levels of cytokines, in particular, interleukins IL4 and IL12, in the brains of HD mice. In addition, the GA-induced effects on BDNF, IL4 and IL12 levels were detected in plasma from drug-treated mice and rats, suggesting utility as a peripheral biomarker of treatment effectiveness. These preclinical studies support the use of GA as a relevant clinical therapy for HD patients.
PMID: 28823953 [PubMed - as supplied by publisher]