G-CSF reduces loss of dopaminergic neurons by inhibiting TNF-α and IL-1β in mouse model of Parkinson’s disease

Abstract

Purpose of the study

granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor existing in neutrophils, glial cells and neurons. Increasing researches discovered that G-CSF improved cell survival in neurodegenerative diseases by its anti-inflammatory effect. However, the effect of G-CSF in suppressing inflammation in Parkinson’s disease (PD) remains unclear. Thus, the purpose of this study is to explored the anti-inflammatory effect of G-CSF in mouse model of PD.

Materials and methods

G-CSF was administrated in the PD model induced by MPTP. Subsequently, the protein of tyrosine hydroxylase (TH), ionized calcium-binding adaptor molecule 1 (Iba-1) and the inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in the midbrain were examined. In addition, the phosphorylated mitogen-activated protein kinases (MAPK) including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK in the midbrain were investigated.

Results

Compared with the MPTP group, the protein of TH in the midbrain was increased, while the Iba-1 and the inflammatory factors were decreased. In addition, the expression of phosphorylated JNK (p-JNK) in the midbrain of the MPTP + G-CSF group was decreased, while the phosphorylated ERK (p-ERK) levels were elevated.

Conclusions

These findings emphasize that G-CSF inhibited the degradation of DA neurons. The protective effect is associated with the reduction of the inflammatory factors caused by the inhibition of the microglial activation. Moreover, G-CSF may decrease the inflammatory factors through the decrease of P-JNK and the increase of P-ERK.

Keywords:

• Parkinson’s disease (PD)
• 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
• granulocyte-colony stimulating factor(G-CSF)
• tyrosine hydroxylase (TH)
• inflammatory factor

Additional information

Funding

The work was supported by the Natural Science Foundation of Ningxia Province under Grant [2018AAC03067]; the National Natural Science Foundation of China under Grant [81260193]; and Ningxia High School First-class Disciplines (West China First-class Disciplines Basic Medical Sciences at Ningxia Medical University) under Grant [NXYLXK2017B07].

Funding

The work was supported by the Natural Science Foundation of Ningxia Province under Grant [2018AAC03067]; the National Natural Science Foundation of China under Grant [81260193]; and Ningxia High School First-class Disciplines (West China First-class Disciplines Basic Medical Sciences at Ningxia Medical University) under Grant [NXYLXK2017B07].