G-CSF improves CUMS-induced depressive behaviors through downregulating Ras/ERK/MAPK signaling pathway.
Neuronal plasticity in hippocampal neurons is closely related to memory, mood and behavior as well as in the development of depression. Granulocyte colony-stimulating factor (G-CSF) can promote neuronal plasticity and enhance motor skills. However, the function of G-CSF in depression remains poorly understood. In this study, we explored the biological role and potential molecular mechanism of G-CSF on depression-like behaviors. Our results showed that G-CSF was significantly downregulated in the hippocampus of chronic unexpected mild stress (CUMS) rats. Administration of G-CSF significantly reversed CUMS-induced depression-like behaviors in the open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Moreover, G-CSF upregulated the expression of synaptic-associated proteins including polysialylated form of neural cell adhesion molecule (PSA-NCAM), synaptophysin (SYN), and postsynaptic density protein 95 (PSD-95) in the hippocampus and G-CSF significantly increased cell viability rate of hippocampal neurons in vitro. Further studies indicated that the renin-angiotensin system (Ras)/extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) signaling pathways was involved in the regulation of G-CSF on depressive-like behaviors and neuronal plasticity in CUMS rats. Taken together, our results showed that G-CSF improves depression-like behaviors via inhibiting Ras/ERK/MAPK signaling pathways. Our study suggests that G-CSF may be a promising therapeutic strategy for the treatment of depression.
Department of Psychiatry and Psychology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
Hui
H
Li
Department of General Internal Medicine, Affiliated Hospital of Yanan University, Yanan, 716000, China; Department of Physiology and Pathophysiology, Health Science Center of Xi'an Jiaotong University, Xi'an, 710004, China.
Linjuan-Li
Department of Psychiatry and Psychology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China. Electronic address: psychiatryxjtu@sina.com.
Yaping
Y
Wang
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological; D018631:ras Proteins / Q000378:metabolism
D000928:Antidepressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D018631:ras Proteins
Depressive behaviors; G-CSF; Hippocampal neurons; Neuronal plasticity; Ras/ERK/MAPK signaling