Neurobiology of aging
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Neurobiology of aging · Dec 2014
Impact of aging on spreading depolarizations induced by focal brain ischemia in rats.
Spreading depolarization (SD) contributes to the ischemic damage of the penumbra. Although age is the largest predictor of stroke, no studies have examined age dependence of SD appearance. We characterized the electrophysiological and hemodynamic changes in young (6 weeks old, n = 7), middle-aged (9 months old, n = 6), and old (2 years old, n = 7) male Wistar rats during 30 minutes of middle cerebral artery occlusion (MCAO), utilizing multimodal imaging through a closed cranial window over the ischemic cortex: membrane potential changes (with a voltage-sensitive dye), cerebral blood volume (green light reflectance), and cerebral blood flow (CBF, laser-speckle imaging) were observed. ⋯ Age reduced the total number of SDs (p < 0.05) but increased the size of ischemic area displaying prolonged SD (p < 0.01). The growth of area undergoing prolonged SDs positively correlated with the growth of ischemic core area (p < 0.01) during MCAO. Prolonged SDs and associated hypoperfusion likely compromise cortical tissue exposed to even a short focal ischemia in aged rats.
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Neurobiology of aging · Dec 2014
Genetic analysis of matrin 3 gene in French amyotrophic lateral sclerosis patients and frontotemporal lobar degeneration with amyotrophic lateral sclerosis patients.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are adult-onset neurodegenerative diseases with overlapping clinical characteristics. They share common genetic causes and pathologic hallmarks such as TDP-43 neuronal accumulations. ⋯ To confirm the contribution of MATR3 to ALS, we studied a French cohort of 153 familial ALS or ALS/FTLD patients, without finding any variant. We conclude that mutations in MATR3 are rare in French familial ALS and ALS with FTLD patients.
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Neurobiology of aging · Nov 2014
Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes.
Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. ⋯ L211P may contribute to its pathogenic effect. The data also suggest that p. R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.
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Neurobiology of aging · Oct 2014
Investigation of TREM2, PLD3, and UNC5C variants in patients with Alzheimer's disease from mainland China.
Recently, 3 rare coding variants significantly associated with Alzheimer's disease (AD) risk have been identified in western populations using whole exome sequencing method, including p. R47H in TREM2, p. V232M in PLD3, and p. ⋯ S843G, and p. V836V) in UNC5C were detected in unrelated patients with late-onset AD. These findings suggest the 3 rare coding variants might not play an important role in AD risk in mainland China.
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Neurobiology of aging · Oct 2014
Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.
Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. ⋯ In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations.