Neurobiology of aging
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Neurobiology of aging · Jun 2010
Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease.
Beta-secretase (BACE1), an enzyme responsible for the production of amyloid beta-peptide (Abeta), is increased by oxidative stress and is elevated in the brains of patients with sporadic Alzheimer's disease (AD). Here, we show that oxidative stress fails to induce BACE1 expression in presenilin-1 (gamma-secretase)-deficient cells and in normal cells treated with gamma-secretase inhibitors. ⋯ Levels of gamma- and beta-secretase activities were greater in brain tissue samples from AD patients compared to non-demented control subjects, and the elevated BACE1 level in the brains of 3xTgAD mice was reduced by treatment with a gamma-secretase inhibitor. Our findings suggest that gamma-secretase mediates oxidative stress-induced expression of BACE1 resulting in excessive Abeta production in AD.
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Neurobiology of aging · Apr 2010
Omega-3 polyunsaturated fatty acids increase the neurite outgrowth of rat sensory neurones throughout development and in aged animals.
Polyunsaturated fatty acids (PUFA) of the omega-3 series and omega-6 series modulate neurite outgrowth in immature neurones. However, it has not been determined if their neurotrophic effects persist in adult and aged tissue. We prepared cultures of primary sensory neurones from male and female rat dorsal root ganglia (DRG), isolated at different ages: post-natal day 3 (P3) and day 9 (P9), adult (2-4 months) and aged (18-20 months). ⋯ The amplitude of the effects was comparable to that of nerve growth factor (NGF; 50ng/ml) and all-trans-retinoic acid (ATRA; 0.1muM). The effects of PUFA were similar in cells positive or negative for the N52 neurofilament marker. Our results show that omega-3 PUFA have a marked neurite-promoting potential in neurones from adult and aged animals.
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Neurobiology of aging · Mar 2010
Randomized Controlled TrialIs age a key determinant of mortality and neurological outcome after acute traumatic spinal cord injury?
Given the potential impact of age on mortality, neurological outcomes and the extent of post-traumatic neural degeneration, we examined these issues using a large, prospectively accrued clinical database (n=485) supplemented by analysis of postmortem spinal cord tissue (n=12) to compare axonal survival and white matter degeneration in younger versus elderly individuals with spinal cord injury (SCI). Elderly individuals (> or = 65 years) had significantly greater mortality rates than younger individuals at 30 days, at 6 months and at 1 year following SCI (46.88% versus 4.86%, respectively; p<0.0001). ⋯ Correspondingly, neuroanatomical analysis of postmortem spinal cord tissue revealed no significant age-related differences for extent of myelin degeneration or number of intact axons within sensory, motor and autonomic spinal cord tracts post-SCI. Treatment protocols for SCI need to identify preventable predictors of mortality in the elderly post-SCI, recognizing that the potential for neurological recovery among elderly survivors of SCI is similar to that of younger individuals.
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Neurobiology of aging · Mar 2010
Age-related slowing of task switching is associated with decreased integrity of frontoparietal white matter.
A body of research has demonstrated age-related slowing on tasks that emphasize cognitive control, such as task switching. However, little is known about the neural mechanisms that contribute to this age-related slowing. To address this issue, the present study used both fMRI and DTI in combination with a standard task switching paradigm. ⋯ Results demonstrated a negative correlation between switch cost RT and FA in left frontoparietal WM in both young and older groups. In addition, age-related FA decline in the same frontoparietal WM region was found to mediate age-related increases in RT switch costs. These findings identify decreased integrity of frontoparietal WM as one mechanism contributing to age-related increases in RT switch costs.
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Neurobiology of aging · Mar 2010
Diffusion tensor imaging of deep gray matter brain structures: effects of age and iron concentration.
Diffusion tensor imaging (DTI) of the brain has become a mainstay in the study of normal aging of white matter, and only recently has attention turned to the use of DTI to examine aging effects in gray matter structures. Of the many changes in the brain that occur with advancing age is increased presence of iron, notable in selective deep gray matter structures. In vivo detection and measurement of iron deposition is possible with magnetic resonance imaging (MRI) because of iron's effect on signal intensity. ⋯ Signal intensity measured with DWI was lower in the putamen of elderly than young adults, whereas the opposite was observed for the white matter region and thalamus. As a retrospective study based on legacy data, the FDRI estimates were based on FSE sequences, which underestimated the classical FDRI index of brain iron. Nonetheless, the differential effects of age on DTI metrics in subcortical gray matter structures compared with white matter tracts appears to be related, at least in part, to local iron content, which in the elderly of the present study was prominent in the FDRI estimate of the putamen and visibly striking in the diffusion-weighted image of the basal ganglia structures.