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Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow
Author(s) -
Park Min Hee,
Jin Hee Kyung,
Min WooKie,
Lee Won Woo,
Lee Jeong Eun,
Akiyama Haruhiko,
Herzog Herbert,
Enikolopov Grigori N,
Schuchman Edward H,
Bae Jaesung
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490174
Subject(s) - biology , haematopoiesis , bone marrow , stem cell , nerve injury , neuropeptide y receptor , microbiology and biotechnology , hematopoietic stem cell , neuropeptide , immunology , cancer research , neuroscience , genetics , receptor
Many reports have revealed the importance of the sympathetic nervous system (SNS) in the control of the bone marrow environment. However, the specific role of neuropeptide Y (NPY) in this process has not been systematically studied. Here we show that NPY‐deficient mice have significantly reduced hematopoietic stem cell (HSC) numbers and impaired regeneration in bone marrow due to apoptotic destruction of SNS fibers and/or endothelial cells. Furthermore, pharmacological elevation of NPY prevented bone marrow impairments in a mouse model of chemotherapy‐induced SNS injury, while NPY injection into conditional knockout mice lacking the Y1 receptor in macrophages did not relieve bone marrow dysfunction. These results indicate that NPY promotes neuroprotection and restores bone marrow dysfunction from chemotherapy‐induced SNS injury through the Y1 receptor in macrophages. They also reveal a new role of NPY as a regulator of the bone marrow microenvironment and highlight the potential therapeutic value of this neuropeptide.