| 1. |
- Gabery, Sanaz, et al.
(författare)
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Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses.
- 2010
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 120, s. 777-788
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a fatal neurodegenerative disorder caused by expansion of a CAG repeat in the HD gene. Degeneration concentrating in the basal ganglia has been thought to account for the characteristic psychiatric symptoms, cognitive decline and motor dysfunction. However, the homeostatic control of emotions and metabolism are disturbed early in HD, and focused studies have identified a loss of orexin (hypocretin) neurons in the lateral hypothalamus in HD patients. There has been limited assessment of other hypothalamic cell populations that may be involved. In this study, we quantified the neuropeptide-expressing hypothalamic neurons known to regulate metabolism and emotion in patients with HD compared to healthy controls using unbiased stereological methods. We confirmed the loss of orexin-expressing neurons in HD and revealed substantial differences in the peptide expression of other neuronal populations in the same patients. Both oxytocin- and vasopressin-expressing neurons were decreased by 45 and 24%, respectively, while the number of cocaine- and amphetamine-regulated transcript (CART)-expressing neurons was increased by 30%. The increased expression of CART in the hypothalamus is consistent with a previous study showing increased CART levels in cerebrospinal fluid from HD patients. There was no difference in the numbers of neuropeptide Y-expressing neurons. These results show significant and specific alterations in the peptide expression of hypothalamic neurons known to regulate metabolism and emotion. They may be important in the development of psychiatric symptoms and metabolic disturbances in HD, and may provide potential targets for therapeutic interventions.
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| 2. |
- Hult Lundh, Sofia, et al.
(författare)
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Hypothalamic and Neuroendocrine Changes in Huntington's Disease.
- 2010
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Ingår i: Current drug targets. - 1873-5592. ; 11, s. 1237-1249
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder without satisfactory treatments nor a cure. It is caused by a CAG repeat expansion in the huntingtin gene. The clinical symptoms involve motor-, cognitive- and psychiatric disturbances. Recent studies have shown that non-motor symptoms and signs, such as mood changes, sleep disturbances and metabolic alterations often occur before the onset of overt motor impairments. The hypothalamus is one of the main regulators of emotion, sleep and metabolism, and it is therefore possible that dysfunction of the hypothalamus and neuroendocrine circuits may, at least partly, be responsible for these non-motor symptoms in HD. Several hypothalamic and neuroendocrine changes have now been identified in clinical HD as well as in rodent models of the disease. These changes could be important both in the pathogenesis of HD, constitute biomarkers to track disease progression as well as to provide novel therapeutic targets for this devastating disease. The current state of knowledge in the area of hypothalamic and neuroendocrine changes in both patients and rodent models of HD is summarized in this review, and their potential as targets for novel treatment paradigms are discussed.
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| 3. |
- Schultz, Kristofer, et al.
(författare)
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Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitors.
- 2010
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Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 17:3, s. 456-460
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. Methods: CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed for the presence of depression. Results: No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors compared to those AD patients who were not. Conclusions: Significant reductions in CSF TTR were found after cholinesterase inhibitor treatment in patients with AD compared to untreated individuals. CSF TTR was unaltered in patients with DLB and had no relationship to depression in the present cohort with dementias.
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