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Recent News and Articles on the Keywords: alzheimer's disease + newborn neurons + neurons  Related to the article below (Last Update: 7/1/2008)

How the Mind Works: Revelations
The New York Review of Books - Jun 5, 2008
The brain is of course tremendously complex: a bundle of some hundred billion neurons, or nerve cells, each sharing as many as ten thousand connections with ...
Source: Google News

Increased hippocampal neurogenesis in Alzheimer's disease -
K Jin, AL Peel, XO Mao, L Xie, BA Cottrell, DC … - Proceedings of the National Academy of Sciences, 2004 - National Acad Sciences
... transgenic mouse model of Alzheimer's disease FASEB J ... Borchelt, and C. Rampon
Alzheimer's-Type Amyloidosis ... Mice Impairs Survival of Newborn Neurons Derived from ...

… : absence at birth, development during the life span, and dissolution in Alzheimer's disease. -
MM Mesulam, C Geula - Ann Neurol, 1988 - ncbi.nlm.nih.gov
... These phylogenetically and ontogenetically progressive neurons are also
markedly vulnerable to degeneration in Alzheimer's disease. ...

Estrogen protects primary cortical neurons from glutamate toxicity -
CA Singer, KL Rogers, TM Strickland, DM Dorsa - Neuroscience Letters, 1996 - Elsevier
... such as that seen in Alzheimer's disease (AD). ... events and in neurodegenera- tive
disease are warranted. ... and the development of the newborn mouse hypothalamus ...

Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw, Ind) mice -
K Jin, V Galvan, L Xie, XO Mao, OF Gorostiza, DE … - Proceedings of the National Academy of Sciences, 2004 - National Acad Sciences
... for example, is associated with migration of newborn neurons from their ... been reported
in patients with Huntington's disease (8) and Alzheimer's disease (AD) (9 ...

Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor … -
HG Kuhn, H Dickinson-Anson, FH Gage - Journal of Neuroscience, 1996 - neuroscience.org
... Facilitates the Morphological Maturation of Newborn Neurons in Adult ... and DA Greenberg
Increased hippocampal neurogenesis in Alzheimer's disease PNAS, January 6 ...

Alzheimer's disease brain extract stimulates the survival of cerebral cortical neurons from neonatal …
Y Uchida, Y Ihara, M Tomonaga - Biochem Biophys Res Commun, 1988 - ncbi.nlm.nih.gov
1988 Feb 15;150(3):1263-7. Click here to read Alzheimer's disease brain extract
stimulates the survival of cerebral cortical neurons from neonatal rats. ...

… colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal … -
CD Toran-Allerand, RC Miranda, WD Bentham, F … - Proc Natl Acad Sci US A, 1992 - pubmedcentral.nih.gov
... Alzheimer's disease and senile dementia: loss of neurons in ... survival of septal
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Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo -
E Arenas, H Persson - Nature, 1994 - palgrave-journals.com
... the death of facial motor neurons in newborn rats 16 ... prevents the degeneration of
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Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP … -
DD Murphy, M Segal - Proceedings of the National Academy of Sciences, 1997 - National Acad Sciences
... and Survival of Newborn Neurons in the ... the estrogen receptor in neurons: Implications
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Deficient Neurogenesis in Forebrain-Specific Presenilin-1 Knockout Mice Is Associated with Reduced … -
R Feng, C Rampon, YP Tang, D Shrom, J Jin, M Kyin, … - Neuron, 2001 - Elsevier
... Alzheimer's Disease (AD) is a degenerative disease of the ... The disease is characterized
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One gene links newborn neurons with those that die in diseases such as Alzheimer's

 
 
In certain parts of the brain, neurons go through a cycle of death and replenishment.
New research from Rockefeller University's Fernando Nottebohm, showed that these replaceable neurons share something in common with the neurons that die in people with diseases such as Alzheimer's and Parkinson's: both have unusually low levels of a protein called UCHL1.

Nottebohm's laboratory has pioneered the study of the brain pathways controlling how songbirds learn to sing. A discrete region of the brains of songbirds, known as the high vocal center, controls their singing behavior. It was in this brain region that, more than 20 years ago, Nottebohm discovered new neurons being born in adult birds, overturning the conventional wisdom that all neurons in vertebrates are created by birth or soon after.

In the new study, the researchers looked at cells in the high vocal center region of the brains of 19 zebra finches, a kind of songbird native to Australia that has long been used in studies of birdsong. Since replaceable neurons sit side-by-side with neurons that are not replaced, the first step was to label the two kinds of cells in order to tell them apart.

The replaceable neurons send projections to another part of the brain a few millimeters away from the high vocal center to form part of the brain pathway that controls muscle movements related to singing. The neurons that are not replaced send their projections to a different brain region, one that controls the song learning pathway. In order to label the two cell types, the scientists injected dyes of different colors, one green and one red, into the brain regions where the neurons project. The dyes then traveled back to the bodies of the cells in the high vocal center. As a result, replaceable and nonreplaceable neurons could easily be distinguished under the microscope.

Then, looking at very thin slices of brain tissue, the researchers used a technique called laser capture microdissection to collect cells of each type. From these they purified RNA, the quantity of which corresponds to the activity of the particular gene producing it. The microdissection technique uses a low-power laser to melt a small circle of film into the tissue. When the film is lifted, the cell body - including its RNA - comes with it, as if removed by a hole punch.

After collecting, purifying, and amplifying the RNA from 3,500 cells for each bird, the researchers used a microarray created in the lab to find out which of the genes in the cells were turned on. This technique allowed them to identify which genes were active, or expressed, by comparing them with 800 known genes from the zebra finch.

They expected to find a few overactive genes in the replaceable neurons. But instead, one gene turned up in consistently low levels.
The gene was UCHL1.

" We expected UCHL1 would be high in all kinds of neurons," says Anthony Lombardino.
The gene is known to be highly expressed throughout the brain, and in fact, the UCHL1 protein is thought to make up as much as 2 percent of total soluble brain protein. But in the zebra finch brains, nonreplaceable neurons produced, on average, about two and a half times the amount of UCHL1 as replaceable neurons.

In addition, studies from other laboratories have pointed to deficiencies in UCHL1 in degenerative diseases such as Alzheimer's and Parkinson's.

Experiments in mice confirmed the finding that low levels of UCHL1 correlate to the ability of neurons to be replaced. The researchers used similar techniques to assess UCHL1 in hippocampus and olfactory bulb neurons in mouse brains, areas where neurons are known to undergo spontaneous replacement. They found markedly low levels of UCHL1 in the replaceable neurons of both these regions.

The scientists also knew that, in songbirds, most neurons born during adulthood die, but a bird's active singing increases the survival rate of new neurons. They reasoned that, if UCHL1 levels are related to the death or survival of neurons, these levels should increase when birds are singing and when more new neurons thus have a chance of surviving. In another experiment the scientists allowed male finches to sing to a female before analyzing the birds' brain neurons. As predicted, the expression of UCHL1 in replaceable neurons, but not in nonreplaceable ones, increased in birds that were singing.

" These findings suggest that rising levels of UCHL1 may be associated with a reduced risk of neuronal death," says Nottebohm. " This study draws attention to the replaceable neurons of adult brain as a wonderful model system in which to study changes in genomic expression related to learning, aging and neurodegeneration, in addition to those that are related to the choreography of replacement itself. "

Source: Proceedings of the National Academy of Sciences ( PNAS ), 2005
 
 
 
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