Granulocyte-colony stimulating factor protects memory impairment in the senescence-accelerated mouse (SAM)-P10

Abstract

Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with memory impairment in elderly people. At present, AD remains incurable. More and more evidences have suggested that granulocyte-colony stimulating factor (G-CSF) has important non-hematopoietic neuroprotective functions in central nervous system. The present study was designed to investigate the therapeutic potential of G-CSF in the senescence-accelerated mouse prone strain (SAM-P10) mice, a mouse model of senile dementia.

Methods: Recombinant human G-CSF was administered subcutaneously in SAM-P10 mice once daily for consecutive 7 days. Morris water maze test was used to evaluate spatial memory of the mice. Immunohistochemistry analysis was done to elucidate the changes of apoptotic neurons in CA1 region of hippocampus of the mice.

Results: In the present study, we found that administration of recombinant G-CSF significantly protected spatial memory impairment, and decreased the number of apoptotic (caspase-3-positive) and tumor necrosis factor related apoptosis-inducing ligand (TRAIL)-positive neurons in CA1 region of hippocampus of SAM-P10 mice, suggesting that G-CSF may protect spatial memory impairment through suppression of TRAIL-mediated apoptosis in neurons.

Conclusions: These findings highlight the therapeutic potential of G-CSF in AD.

Keywords:

• Alzheimer’s disease
• Granulocyte-colony stimulating factor
• Memory loss
• Apoptosis
• senescence-accelerated mouse (SAM)-P10