The ageing systemic milieu negatively regulates neurogenesis and cognitive function

Saul A. Villeda, Jian Luo, Kira I. Mosher, Bende Zou, Markus Britschgi, Gregor Bieri, Trisha M. Stan, Nina Fainberg, Zhaoqing Ding, Alexander Eggel, Kurt M. Lucin, Eva Czirr, Jeong Soo Park, Sebastien Couillard-Després, Ludwig Aigner, Ge Li, Elaine R. Peskind, Jeffrey Kaye, Joseph Quinn, Douglas R. Galasko & 3 others Xinmin S. Xie, Thomas A. Rando, Tony Wyss-Coray

Research output: Contribution to journalArticle

745 Citations (Scopus)

Abstract

In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines-including CCL11 (also known as eotaxin)-the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.

Original languageEnglish (US)
Pages (from-to)90-96
Number of pages7
JournalNature
Volume477
Issue number7362
DOIs
StatePublished - Sep 1 2011

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Neurogenesis
Cognition
Chemokine CCL11
Parabiosis
Adult Stem Cells
Neuronal Plasticity
Neural Stem Cells
Fear
Cerebrospinal Fluid
Stem Cells
Central Nervous System
Learning

ASJC Scopus subject areas

  • General

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Villeda, S. A., Luo, J., Mosher, K. I., Zou, B., Britschgi, M., Bieri, G., ... Wyss-Coray, T. (2011). The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 477(7362), 90-96. https://doi.org/10.1038/nature10357

The ageing systemic milieu negatively regulates neurogenesis and cognitive function. / Villeda, Saul A.; Luo, Jian; Mosher, Kira I.; Zou, Bende; Britschgi, Markus; Bieri, Gregor; Stan, Trisha M.; Fainberg, Nina; Ding, Zhaoqing; Eggel, Alexander; Lucin, Kurt M.; Czirr, Eva; Park, Jeong Soo; Couillard-Després, Sebastien; Aigner, Ludwig; Li, Ge; Peskind, Elaine R.; Kaye, Jeffrey; Quinn, Joseph; Galasko, Douglas R.; Xie, Xinmin S.; Rando, Thomas A.; Wyss-Coray, Tony.

In: Nature, Vol. 477, No. 7362, 01.09.2011, p. 90-96.

Research output: Contribution to journalArticle

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, J, Quinn, J, Galasko, DR, Xie, XS, Rando, TA & Wyss-Coray, T 2011, 'The ageing systemic milieu negatively regulates neurogenesis and cognitive function', Nature, vol. 477, no. 7362, pp. 90-96. https://doi.org/10.1038/nature10357
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Sep 1;477(7362):90-96. https://doi.org/10.1038/nature10357
Villeda, Saul A. ; Luo, Jian ; Mosher, Kira I. ; Zou, Bende ; Britschgi, Markus ; Bieri, Gregor ; Stan, Trisha M. ; Fainberg, Nina ; Ding, Zhaoqing ; Eggel, Alexander ; Lucin, Kurt M. ; Czirr, Eva ; Park, Jeong Soo ; Couillard-Després, Sebastien ; Aigner, Ludwig ; Li, Ge ; Peskind, Elaine R. ; Kaye, Jeffrey ; Quinn, Joseph ; Galasko, Douglas R. ; Xie, Xinmin S. ; Rando, Thomas A. ; Wyss-Coray, Tony. / The ageing systemic milieu negatively regulates neurogenesis and cognitive function. In: Nature. 2011 ; Vol. 477, No. 7362. pp. 90-96.
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