Granulocyte colony-stimulating factor attenuates chronic neuroinflammation in the brain of amyloid precursor protein transgenic mice: an Alzheimer's disease mouse model

J Int Med Res. 2010 Jul-Aug;38(4):1305-12. doi: 10.1177/147323001003800412.

Abstract

Recent evidence suggests that inflammatory mechanisms contribute significantly to the progression of Alzheimer's disease. Granulocyte colony-stimulating factor (G-CSF) is an anti-inflammatory immunomodulator, but the mechanism of its anti-inflammatory effect is unclear. This study was designed to investigate whether G-CSF could inhibit inflammation in a mouse model of Alzheimer's disease through an α7 nicotinic acetylcholine receptor (α7 nAChR) pathway. Mice transgenic for the V171I mutant amyloid precursor protein (APP) were injected subcutaneously with G-CSF 50 μg/kg per day or phosphate-buffered saline (PBS; control group) for 7 days, and wild-type C57/BL6 mice were injected with PBS daily for 7 days. Mice were killed on days 7, 14 and 28 after treatment began. Levels of α7 nAChR protein were significantly increased and levels of interleukin-1β, tumour necrosis factor-α and nuclear factor-κB (NF-κB) protein were significantly decreased in the brain of APP transgenic mice in response to G-CSF. Levels of α7 nAChR protein correlated negatively with NF-κB levels. It is concluded that G-CSF might attenuate inflammation by down-regulating NF-κB and up-regulating α7 nAChR in the brain of APP transgenic mice, indicating a potential new therapeutic approach to Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / drug effects
  • Brain / pathology*
  • Chronic Disease
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Inflammation / drug therapy*
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Receptors, Nicotinic / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Amyloid beta-Protein Precursor
  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Interleukin-1beta
  • NF-kappa B
  • Receptors, Nicotinic
  • Tumor Necrosis Factor-alpha
  • alpha7 Nicotinic Acetylcholine Receptor
  • Granulocyte Colony-Stimulating Factor