This is unpublished research from one of the groups who recently published some related work on parabiosis and cognitive structure and function, discussed in this forum here. The new, unpublished work:
http://www.alzforum....oglia-cognition
Gabrielle Strobel
As the brain ages, its microglial cells [the brain's resident immune cell, responsible for degrading beta-amyloid amongst other things] turn sluggish in their task of ingesting and degrading toxic products, and the flow of blood through its micro vessels slows. ... Tony Wyss-Coray of Stanford University ... [showed that] the microglial activation marker CD68, a lysosomal protein, rises with age. Electron micrographs of aging brain show microglia with an enlarged, dense nucleus, shriveled Golgi cisternae, few lysosomes, and vesicles jammed with lipufuscin granules ... hardly phagocytosing in culture when presented with their usual substrates.
[Parabiotic] paring of an 18-month-old with a 3-month-old mouse, and letting them live together for five weeks, reversed microglial aging. ... CD68 expression was down in the brains of old mice exposed to young blood. In the electron microscope, the old mices microglia looked like those of young mice, with a normal-sized, light nucleus, larger Golgi cisternae, more lysosomes, and less lipofuscin.
To the eyes of some scientists at the conference, the nucleus in microglia from old mice looked as if it contained dense chromatin that would allow less protein translation. Wyss-Coray replied that he does not know for sure how the ultrastructural changes in aging microglia relate to gene expression and function. ... [but parabiosis in old mice] largely reverse the gene expression phenotype of microglial aging. This includes age-related increases not only in CD68 and in the complement component C1qB; but also age-related decreases in progranulin, the transcription factor EGR1, and many other expression changes.
In a separate study, Ingenuity Pathway Analysis of gene expression profiles of the aging hippocampus pointed to a synaptic plasticity network anchored by the transcription factors Creb (cAMP response element-binding protein) and EGR1 as being most preserved in rejuvenated old mice. Golgi silver staining spotted more spines on the dendrites of old mice when each had each partnered with a young mouse. A paper published by Wyss-Coray and his former postdoc Saul Villeda and colleagues on May 4 in Nature Medicine reports additional findings ... These include strengthened long-term potentiation as seen with electrophysiology of cultured hippocampal slices ...
[O]ld mice INJECTED with plasma from young mice outperformed untreated old mice in the radial arm water maze and a fear-conditioning test... [and show] more neurogenesis, synaptic plasticity, spine density, and less neuroinflammation. The effects are not due to steroid hormones...
In a recent review article arguing for a return of parabiosis to study the pathophysiology of age-related disease, Wyss-Coray writes that paired mice fare better than many other animal models exposed to pathogens, traumatic injuries, cancer, or debilitating mutations (Eggel and Wyss-Coray, 2014). In Los Angeles, he noted unpublished recovery data showing that the pairs resumed grooming and nesting, and lived a full lifespan.
