Young bone marrow transplantation preserves learning and memory in old mice

Melanie M Das; Marlesa Godoy; Shuang Chen; V Alexandra Moser; Pablo Avalos; Kristina M Roxas; Ivy Dang; Alberto Yáñez; Wenxuan Zhang; Catherine Bresee; Moshe Arditi; George Y Liu; Clive N Svendsen; Helen S Goodridge

doi:10.1038/s42003-019-0298-5

Young bone marrow transplantation preserves learning and memory in old mice

Commun Biol. 2019 Feb 20:2:73. doi: 10.1038/s42003-019-0298-5. eCollection 2019.

Authors

Melanie M Das^{1

2}, Marlesa Godoy^{1

2}, Shuang Chen^{2

3}, V Alexandra Moser^{1

2}, Pablo Avalos^{1

2}, Kristina M Roxas^{1

2}, Ivy Dang^{1

2}, Alberto Yáñez^{1

2}, Wenxuan Zhang^{2

3}, Catherine Bresee⁴, Moshe Arditi^{2

3}, George Y Liu^{2

3}, Clive N Svendsen^{5

6}, Helen S Goodridge^{7

8}

Affiliations

¹ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
² Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
³ Department of Pediatrics, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
⁴ Biostatistics and Bioinformatics Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
⁵ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. clive.svendsen@csmc.edu.
⁶ Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. clive.svendsen@csmc.edu.
⁷ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. helen.goodridge@csmc.edu.
⁸ Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. helen.goodridge@csmc.edu.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Aging / physiology*
Animals
Bone Marrow Transplantation / methods*
Chemokine CCL11 / blood
Cognition / physiology*
Hippocampus / cytology
Hippocampus / physiology
Learning / physiology*
Male
Memory / physiology*
Mice, Congenic
Mice, Inbred C57BL
Mice, Transgenic
Neurogenesis / physiology
Rejuvenation / physiology*
beta 2-Microglobulin / metabolism

Substances

Chemokine CCL11
beta 2-Microglobulin