Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-β induced experimental model of Alzheimer's disease

GCSF is an endogenous neuronal hematopoietic factor that displays robust in vitro and in vivo neuroprotective activity. The present study aimed to evaluate the effect of GCSF on A beta-induced memory loss in an Alzheimer's disease model of rats. A total of 42 male adult Wistar rats weighing 200-250 g were used in the study and were divided into 7 experimental groups. Animals were subjected to intracerebroventricular (ICV) injection stereotaxically at day 0 to instill amyloid-beta(1-42) (A beta(1-42)) or PBS (sham operated group) at 10 mu l (5 mu l bilaterally). GCSF treatment was given from day 7 to 12 of A beta injection. On day 21, behavioral tests (short term memory, exploratory behavior and motor coordination) in all groups were evaluated. Biochemical parameters and RNA expression were measured to ensure the efficacy of GCSF. GCSF (35 and 70 mu g/kg, s.c.) showed statistically significant improvement in memory as compared to control and sham operated groups (p < 0.05). Mean time spent in the platform placed quadrant was found to be significantly increased in the GCSF (70 mu g/kg, s.c.) as compared to GCSF (35 mu g/kg, s.c.) and GCSF (10 mu g/kg, s.c.) groups (p < 0.001). GCSF (35 and 70 mu g/kg, s.c.) also improved motor coordination and exploratory behavior significantly as compared to naive sham operated and GCSF (10 mu g/kg, s.c.) groups (p < 0.05). Improvement in memory by GCSF (35 and 70 mu g/kg, s.c.) was coupled with marked reduction of lipid peroxidation, acetylcholinesterase levels and a significant increase in antioxidant enzymes as well as total RNA expression in the brain. Additionally, GCSF (35 and 70 mu g/kg, s.c.) significantly increased progenitor cells (iPSCs) and surface marker CD34+ in the brain and hence induced neurogenesis. The present findings demonstrate an improvement of memory and neurobehavioral function with GCSF in A beta-induced Alzheimer's disease model in rats. (C) 2013 Elsevier Inc. All rights reserved.