88 research outputs found
Impaired Adult Neurogenesis in the Dentate Gyrus of a Triple Transgenic Mouse Model of Alzheimer's Disease
It has become generally accepted that new neurones are added and integrated mainly in two areas of the mammalian CNS, the subventricular zone and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus, which is of central importance in learning and memory. The newly generated cells display neuronal morphology, are able to generate action potentials and receive functional synaptic inputs, i.e. their properties are similar to those found in mature neurones. Alzheimer's disease (AD) is the primary and widespread cause of dementia and is an age-related, progressive and irreversible neurodegenerative disease that deteriorates cognitive functions. Here, we have used male and female triple transgenic mice (3xTg-AD) harbouring three mutant genes (β-amyloid precursor protein, presenilin-1 and tau) and their respective non-transgenic (non-Tg) controls at 2, 3, 4, 6, 9 and 12 months of age to establish the link between AD and neurogenesis. Using immunohistochemistry we determined the area density of proliferating cells within the SGZ of the DG, measured by the presence of phosphorylated Histone H3 (HH3), and their possible co-localisation with GFAP to exclude a glial phenotype. Less than 1% of the HH3 labeled cells co-localised with GFAP. Both non-Tg and 3xTg-AD showed an age-dependent decrease in neurogenesis. However, male 3xTg-AD mice demonstrated a further reduction in the production of new neurones from 9 months of age (73% decrease) and a complete depletion at 12 months, when compared to controls. In addition, female 3xTg-AD mice showed an earlier but equivalent decrease in neurogenesis at 4 months (reduction of 63%) with an almost inexistent rate at 12 months (88% decrease) compared to controls. This reduction in neurogenesis was directly associated with the presence of β-amyloid plaques and an increase in the number of β-amyloid containing neurones in the hippocampus; which in the case of 3xgTg females was directly correlated. These results suggest that 3xTg-AD mice have an impaired ability to generate new neurones in the DG of the hippocampus, the severity of which increases with age and might be directly associated with the known cognitive impairment observed from 6 months of age onwards . The earlier reduction of neurogenesis in females, from 4 months, is in agreement with the higher prevalence of AD in women than in men. Thus it is conceivable to speculate that a recovery in neurogenesis rates in AD could help to rescue cognitive impairment
Planetary Rings
Planetary rings are the only nearby astrophysical disks, and the only disks
that have been investigated by spacecraft. Although there are significant
differences between rings and other disks, chiefly the large planet/ring mass
ratio that greatly enhances the flatness of rings (aspect ratios as small as
1e-7), understanding of disks in general can be enhanced by understanding the
dynamical processes observed at close-range and in real-time in planetary
rings. We review the known ring systems of the four giant planets, as well as
the prospects for ring systems yet to be discovered. We then review planetary
rings by type. The main rings of Saturn comprise our system's only dense broad
disk and host many phenomena of general application to disks including spiral
waves, gap formation, self-gravity wakes, viscous overstability and normal
modes, impact clouds, and orbital evolution of embedded moons. Dense narrow
rings are the primary natural laboratory for understanding shepherding and
self-stability. Narrow dusty rings, likely generated by embedded source bodies,
are surprisingly found to sport azimuthally-confined arcs. Finally, every known
ring system includes a substantial component of diffuse dusty rings. Planetary
rings have shown themselves to be useful as detectors of planetary processes
around them, including the planetary magnetic field and interplanetary
impactors as well as the gravity of nearby perturbing moons. Experimental rings
science has made great progress in recent decades, especially numerical
simulations of self-gravity wakes and other processes but also laboratory
investigations of coefficient of restitution and spectroscopic ground truth.
The age of self-sustained ring systems is a matter of debate; formation
scenarios are most plausible in the context of the early solar system, while
signs of youthfulness indicate at least that rings have never been static
phenomena.Comment: 82 pages, 34 figures. Final revision of general review to be
published in "Planets, Stars and Stellar Systems", P. Kalas and L. French
(eds.), Springer (http://refworks.springer.com/sss
Origin of the orbital architecture of the giant planets of the Solar System
Nature, 435, pp. 459-461, http://dx.doi.org./10.1038/nature03539International audienc
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