Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow.
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.
Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea.
Min Hee
MH
Park
Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
Hee Kyung
HK
Jin
Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Korea.
Woo-Kie
WK
Min
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.
Won Woo
WW
Lee
Department of Radiation Oncology, Kyungpook National University Hospital, Daegu, Korea.
Jeong Eun
JE
Lee
Department of Orthopaedics, Kyoto University, Kyoto, Japan.
Haruhiko
H
Akiyama
Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Herbert
H
Herzog
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Grigori N
GN
Enikolopov
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Edward H
EH
Schuchman
Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea jsbae@knu.ac.kr.
Jae-sung
JS
Bae
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells / Q000378:metabolism*; D060833:Cellular Microenvironment / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009478:Neuropeptide Y / Q000172:deficiency / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000166:cytology
D009478:Neuropeptide Y
bone marrow microenvironment; hematopoietic stem cell; neuropeptide Y; regeneration; sympathetic nervous system