title: The ageing systemic milieu negatively regulates neurogenesis and cognitive function.
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.
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
authors: Saul A
authors: SA
authors: Villeda
authors: Jian
authors: J
authors: Luo
authors: Kira I
authors: KI
authors: Mosher
authors: Bende
authors: B
authors: Zou
authors: Markus
authors: M
authors: Britschgi
authors: Gregor
authors: G
authors: Bieri
authors: Trisha M
authors: TM
authors: Stan
authors: Nina
authors: N
authors: Fainberg
authors: Zhaoqing
authors: Z
authors: Ding
authors: Alexander
authors: A
authors: Eggel
authors: Kurt M
authors: KM
authors: Lucin
authors: Eva
authors: E
authors: Czirr
authors: Jeong-Soo
authors: JS
authors: Park
authors: Sebastien
authors: S
authors: Couillard-Després
authors: Ludwig
authors: L
authors: Aigner
authors: Ge
authors: G
authors: Li
authors: Elaine R
authors: ER
authors: Peskind
authors: Jeffrey A
authors: JA
authors: Kaye
authors: Joseph F
authors: JF
authors: Quinn
authors: Douglas R
authors: DR
authors: Galasko
authors: Xinmin S
authors: XS
authors: Xie
authors: Thomas A
authors: TA
authors: Rando
authors: Tony
authors: T
authors: Wyss-Coray
mesh_terms: D000375:Aging; D000818:Animals; D054413:Chemokine CCL11 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000494:pharmacology; D018925:Chemokines / Q000097:blood* / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D007859:Learning Disabilities / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D010227:Parabiosis; D010949:Plasma / Q000737:chemistry; D013997:Time Factors
chemical_list: D054413:Chemokine CCL11; D018925:Chemokines