Hypothalamic pathology in Huntington's disease.

Motor disturbances, cognitive decline and psychiatric symptoms are considered as the key symptoms of Huntington__s disease (HD). Yet, other prevalent features include unintended weight loss, sleep and circadian disturbances and autonomic nervous system dysfunction. The nature of these features supports a pivotal role of the hypothalamus in the HD disease process. In this thesis data is presented from immunocytochemical and in situ hybridization studies demonstrating substantial pathology in hypothalamic neuropeptide expression in HD patients. Main findings include neuropeptide changes in the suprachiasmatic nucleus, the body__s master clock, that will likely be responsible for disruption of 24h circadian rhythmicity. Secondly, the neuronal histaminergic system is hyperactive at both the level of the hypothalamic tuberomamillary nucleus as well as in the cerebral neocortex. These changes could partly explain weight loss and cognitive decline in patients. The expression of neuropeptides in the hypothalamic paraventricular and infundibular nuclei, however, seems to be relatively unaffected by the HD disease process. Finally, a discrepancy between mRNA expression and protein expression of many hypothalamic neuropeptides was observed that can be partly explained by a decrease of prohormone convertase expression. Interestingly, hypothalamic changes in existing HD transgenic rodent models are largely non-representative of hypothalamic changes in HD patients.Cure Huntington’s Disease Initiative (CHDI) Foundation, Inc (project ID A-2376)UBL - phd migration 201

Hypothalamic Alterations in Huntington's Disease Patients: Comparison with Genetic Rodent Models

Neurological Motor Disorder

Paraventricular Nucleus Neuropeptide Expression in Huntington's Disease Patients

Neurological Motor Disorder

Neuropeptide alterations in the infundibular nucleus of Huntington's disease patients.

Data from transgenic mouse models of Huntington's disease (HD) suggest that dysfunction of the hypothalamic infundibular nucleus (INF) (in rodents, the arcuate nucleus) may contribute to unintended weight loss and insatiable appetite among HD patients. Using post-mortem paraffin-embedded tissue, we assessed the total number of INF neurones by thionin staining and four major regulatory neuropeptides in the INF of HD patients by immunocytochemistry and in situ hybridisation. In HD patients, the total number of neurones in the INF was unchanged compared to control subjects (P = 0.92), whereas it contained over 30% less neuropeptide Y-immunoreactive (IR) neurones (P = 0.016), as well as reduced peptide levels, in fibres to the paraventricular and ventromedial nucleus (P = 0.003, P = 0.005, respectively). Conversely, neuropeptide Y mRNA expression levels were increased three-fold (P = 0.047). No changes were observed in the number of neurones immunoreactive for α-melanocyte-stimulating hormone, agouti-related peptide, and cocaine- and amphetamine-regulated transcript (P ≥ 0.17). Our findings suggest changes in the pathology of the INF neuropeptide Y-expressing neurones in HD patients without changes in other (an)orexigenic neuropeptides and without neuronal cell loss. These findings indicate that unintended weight loss in patients suffering from this disease may be partly a result of neuropeptidergic alterations in the hypothalamic infundibular nucleu

Central neurogenic hyperventilation due to pontine glioma

Paroxysmal Cerebral Disorder

Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases

Study Objectives: Neuronal histamine shows diurnal rhythms in rodents and plays a major role in the maintenance of vigilance. No data are available on its diurnal fluctuation in humans, either in health or in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD), or Huntington disease (HD), all of which are characterized by sleep-wake disturbances. Design: Quantitative in situ hybridization was used to study the mRNA expression of histidine decarboxylase (HDC), the key enzyme of histamine production in the tuberomammillary nucleus (TMN) in postmortem human hypothalamic tissue, obtained from 33 controls and 31 patients with a neurodegenerative disease-PD (n = 15), AD (n = 9), and HD (n = 8)-and covering the full 24-h cycle with respect to clock time of death. Results: HDC-mRNA levels in controls were found to be significantly higher during the daytime than at night (e.g., 08:01-20:00 versus 20:01-08:00, P = 0.004). This day-night fluctuation was markedly different in patients with neurodegenerative diseases. Conclusion: The diurnal fluctuation of HDC-mRNA expression in human TMN supports a role for neuronal histamine in regulating day-night rhythms. Future studies should investigate histamine rhythm abnormalities in neurodegenerative disorders

Billiards-related dystonia: A new task-specific dystonia

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Functional Increase of Brain Histaminergic Signaling in Huntington's Disease

Neurological Motor Disorder

Decreased hypothalamic prohormone convertase expression in Huntington disease patients.

Neurological Motor Disorder