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- Chung, Sun Ju, et al.
(författare)
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Alpha-Synuclein Repeat Variants and Survival in Parkinson's Disease
- 2014
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 29:8, s. 1053-1057
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine whether alpha-synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD). Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow-up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival. Results: Twenty-one sites contributed data for 6,154 cases. There was no significant association between alpha-synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01-1.10; P value = 0.01). Conclusions: In our large consortium study, alpha-synuclein REP1 genotypes were not associated with survival in PD. Further studies of alpha-synuclein's role in disease progression and long-term outcomes are needed. (C) 2014 International Parkinson and Movement Disorder Society
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- Palomba, M, et al.
(författare)
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Decline of the presynaptic network, including GABAergic terminals, in the aging suprachiasmatic nucleus of the mouse
- 2008
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Ingår i: Journal of biological rhythms. - : SAGE Publications. - 0748-7304 .- 1552-4531. ; 23:3, s. 220-231
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Tidskriftsartikel (refereegranskat)abstract
- Biological rhythms, and especially the sleep/wake cycle, are frequently disrupted during senescence. This draws attention to the study of aging-related changes in the hypothalamic suprachiasmatic nucleus (SCN), the master circadian pacemaker. The authors here compared the SCN of young and old mice, analyzing presynaptic terminals, including the gamma-aminobutyric acid (GABA)ergic network, and molecules related to the regulation of GABA, the main neurotransmitter of SCN neurons. Transcripts of the α3 subunit of the GABAA receptor and the GABA-synthesizing enzyme glutamic acid decarboxylase isoform 67 (GAD67) were analyzed with real-time RT-PCR and GAD67 protein with Western blotting. These parameters did not show significant changes between the 2 age groups. Presynaptic terminals were identified in confocal microscopy with synaptophysin immunofluorescence, and the GABAergic subset of those terminals was revealed by the colocalization of GAD67 and synaptophysin. Quantitative analysis of labeled synaptic endings performed in 2 SCN subregions, where retinal afferents are known to be, respectively, very dense or very sparse, revealed marked aging-related changes. In both subregions, the evaluated parameters (the number of and the area covered by presynaptic terminals and by their GABAergic subset) were significantly decreased in old versus young mice. No significant differences were found between SCN tissue samples from animals sacrificed at different times of day, in either age group. Altogether, the data point out marked reduction in the synaptic network of the aging biological clock, which also affects GABAergic terminals. Such alterations could underlie aging-related SCN dysfunction, including low-amplitude output during senescence.
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