Abstract

Restoration of cognitive function in old mice by transfer of blood or plasma from young mice has been attributed to reduced C–C motif chemokine ligand 11 (CCL11) and β2-microglobulin, which are thought to suppress neurogenesis in the aging brain. However, the specific role of the hematopoietic system in this rejuvenation has not been defined and the importance of neurogenesis in old mice is unclear. Here we report that transplantation of young bone marrow to rejuvenate the hematopoietic system preserved cognitive function in old recipient mice, despite irradiation-induced suppression of neurogenesis, and without reducing β2-microglobulin. Instead, young bone marrow transplantation preserved synaptic connections and reduced microglial activation in the hippocampus. Circulating CCL11 levels were lower in young bone marrow recipients, and CCL11 administration in young mice had the opposite effect, reducing synapses and increasing microglial activation. In conclusion, young blood or bone marrow may represent a future therapeutic strategy for neurodegenerative disease.

Melanie Das et al. demonstrate that transplantation of young bone marrow preserves the cognitive function of old recipient mice. This study suggests that microglial rejuvenation via peripheral manipulation of the hematopoietic system may be sufficient to delay a cognitive decline during aging.

Details

Title
Young bone marrow transplantation preserves learning and memory in old mice
Author
Das, Melanie M 1 ; Godoy Marlesa 1 ; Chen, Shuang 2 ; Alexandra, Moser V 1 ; Avalos, Pablo 1 ; Roxas, Kristina M 1 ; Dang Ivy 1 ; Yáñez, Alberto 1 ; Zhang, Wenxuan 2 ; Bresee, Catherine 3 ; Arditi Moshe 2 ; Liu, George Y 2 ; Svendsen, Clive N 1 ; Goodridge, Helen S 1 

 Cedars-Sinai Medical Center, Board of Governors Regenerative Medicine Institute, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905); Cedars-Sinai Medical Center, Department of Biomedical Sciences, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905) 
 Cedars-Sinai Medical Center, Department of Biomedical Sciences, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905); Cedars-Sinai Medical Center, Department of Pediatrics, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905) 
 Cedars-Sinai Medical Center, Biostatistics and Bioinformatics Research Institute, Los Angeles, USA (GRID:grid.50956.3f) (ISNI:0000 0001 2152 9905) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2382024595
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.