Villeda and colleagues reached this conclusion via parabiosis experiments in which they sutured the abdominal lining of a young mouse to that of an older mouse. The capillary beds fused, allowing the mice to exchange blood for two months. While neurogenesis in the dentate gyrus dropped in young mice subjected to the procedure, neuron production boomed threefold in the old mice. The researchers traced the neuron bust in young mice to blood-borne factors from the older animals—in particular, the chemokine eotaxin (also known as CCL11), which plays a role in allergic responses. Plasma CCL11 increases with age in both mice and humans, the researchers found. Systemically injecting eotaxin alone into young mice inhibited neurogenesis, confirming its central role.

The paper correlates these neurogenesis effects to deficits in learning and memory. Young mice who received either old blood or systemic eotaxin injections showed less long-term potentiation in the dentate gyrus than normal young mice, and also learned poorly in the water maze and in fear conditioning tests. The learning problems matched those of young mice whose neural stem cells had been ablated by radiation, suggesting that the lack of new neurons might be to blame for memory problems. But exactly how eotaxin causes these deficits is unclear. One question is whether it can directly affect the brain, or whether it acts through other plasma factors. To get at this question, the researchers injected eotaxin directly into the dentate gyrus, and again saw a dampening of neurogenesis. Importantly, when the researchers also injected an eotaxin-neutralizing antibody, neurogenesis remained high. The results suggest that the factor might act directly in the brain.

In an accompanying editorial, Richard Ransohoff at the Cleveland Clinic, Ohio, notes these data suggest that “factors that alter neurogenesis, such as exercise or systemic inflammation, might act by modifying the abundance of signaling proteins in the blood plasma.” It is not clear if eotaxin acts directly on stem cells, Ransohoff points out, as its receptor, CCR3, is not typically found on stem and progenitor cells. Ransohoff speculates that eotaxin could be acting on microglia, which are known to dampen neurogenesis under some conditions, or it might be suppressing interleukin-4, which normally acts to restrain brain inflammation that might otherwise impair neurogenesis. Though the mechanisms remain to be determined, “the good news from this report is that neural stem cells in the aging brain do not undergo irreversible decline and can respond to a favourable environment,” Ransohoff wrote.—Madolyn Bowman Rogers.

References:
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Aug 31. Abstract

Ransohoff RM. Blood ties. Nature. 2011 Aug 31. Abstract