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.