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Forschungsdatenbank PMU-SQQUID

The ageing systemic milieu negatively regulates neurogenesis and cognitive function
Villeda, SA; Luo, J; Mosher, KI; Zou, BD; Britschgi, M; Bieri, G; Stan, TM; Fainberg, N; Ding, ZQ; Eggel, A; Lucin, KM; Czirr, E; Park, JS; Couillard-Despres, S; Aigner, L; Li, G; Peskind, ER; Kaye, JA; Quinn, JF; Galasko, DR; Xie, XMS; Rando, TA; Wyss-Coray, T
NATURE. 2011; 477(7362): 90-U157.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Couillard-Després Sébastien

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(1). Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise(1). 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.


Useful keywords (using NLM MeSH Indexing)

Aging

Animals

Chemokine CCL11/blood

Chemokine CCL11/cerebrospinal fluid

Chemokine CCL11/metabolism

Chemokine CCL11/pharmacology

Chemokines/blood*

Chemokines/cerebrospinal fluid

Chemokines/metabolism*

Female

Learning/drug effects

Learning/physiology*

Learning Disorders/blood

Learning Disorders/cerebrospinal fluid

Learning Disorders/physiopathology

Male

Memory Disorders/blood

Memory Disorders/cerebrospinal fluid

Memory Disorders/physiopathology

Mice

Mice, Inbred C57BL

Neurogenesis/drug effects

Neurogenesis/physiology*

Parabiosis

Plasma/chemistry

Time Factors