The investigators then turned to the question of precisely what, inblood, was producing the effect. To rule out the possibility thatan exchange of cells between the young and old mice wasresponsible, they created circulation-sharing young/old mousepairs, one of whose members had been genetically engineered so thatevery one of its cells would glow green when exposed to light. Ineach case, green cells from the modified mouse turned up in theblood of the other mouse in the pair, as might be expected, butvirtually never in the brain of the non-modified mouse. Clearly,some other substances besides cells from each mouse's blood wereaffecting its partner's brain. Moreover, when plasma - the cell-free fraction of blood - from oldmice was injected into young mice, it wrought the same deleteriouschanges in their dentate gyrus as if they'd been sharing blood witholder mice.
And on spatial-navigation tasks, such as finding a highspot to rest on in a water-filled chamber, young mice who hadreceived injections of older mice's plasma performed more poorlythan a group that got injections of plasma from younger mice. The"old-blood" mice seemed to learn the desirable location as easilyas the "youngbloods" did - but they forgot it more quickly, a signof impaired hippocampal function. To identify specific circulating factors associated with aging andtissue degeneration or tissue regeneration, the researchers assayed66 different immune-signaling proteins found in mice's blood. Sixof these factors were elevated in both unpaired old mice and youngmice that had been paired with older ones.
At the top of the list was eotaxin, a small protein that attracts acertain type of immune cells to areas where it has been secreted byother types of cells. Highlighting this discovery's possiblerelevance to humans, tests that Wyss-Coray's team conducted onblood and cerebrospinal fluid samples drawn from healthy peoplebetween the ages of 20 and 90 showed a parallel age-relatedincrease in eotaxin. In humans, eotaxin is associated with allergicresponses and asthma . Normal young-adult mice given eotaxin injections exhibiteddeficient generation of new nerve cells in their dentate gyrus.
Sodid both young mice administered plasma from old mice and youngmice whose circulatory systems were joined with those of old mice -an effect that could be countered by injections of anothersubstance that blocks eotaxin's action. Eotaxin injections alsoimpaired performance on spatial-memory tests. Other blood-borne factors are probably significant players inaging-related declines in cognitive function. One of the sixsubstances identified in the protein screen by Wyss-Coray's groupwas MCP-1, a chemical that, in mice and humans, attracts immunecells called macrophages. Associate professor of neurosurgery TheoPalmer, PhD, has previously linked inflammation-triggeredelevations of MCP-1 levels to reduced stem-cell numbers in thedentate gyrus.
The Wyss-Coray group is now testing eotaxin's potential role inmemory loss associated with Alzheimer's disease , and is developing expanded blood-protein assays in a hunt for"rejuvenating" factors in blood that may prove useful in treating dementia and, perhaps, slowing the aging process in older brains. The study was funded by the U.S. Department of Veterans Affairs,the National Institutes of Health, the National Institute on Agingand the California Institute for Regenerative Medicine. AdditionalStanford co-authors were visiting assistant professor Jeong-SooPark, PhD, now at Dankook University in Cheonan, South Korea;postdoctoral researchers Markus Britschgi, PhD, (now at F.Hoffman-La Roche Ltd., Basel, Switzerland), Kurt Lucin, PhD, EvaCzirr, PhD, and Alexander Eggel, PhD; instructor Jian Luo, MD, PhD;graduate students Kira Mosher, Gregor Bieri, Trisha Stan andZhaoqing Ding; and research associate Nina Fainberg.
Information on Stanford's Department of Neurology and NeurologicalSciences, which also supported the work, is available at neurology.stanford.edu/ . Additional References Citations. I am an expert from Crude Oil, usually analyzes all kind of industries situation, such as stovetop espresso maker , microwave plastic plate.
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