title: Granulocyte colony stimulating factor (GCSF) improves memory and neurobehavior in an amyloid-β induced experimental model of Alzheimer's disease.
abstract: 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 Aβ-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-β(1-42) (Aβ(1-42)) or PBS (sham operated group) at 10 μl (5 μl bilaterally). GCSF treatment was given from day 7 to 12 of Aβ 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 μg/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 μg/kg, s.c.) as compared to GCSF (35 μg/kg, s.c.) and GCSF (10 μg/kg, s.c.) groups (p<0.001). GCSF (35 and 70 μg/kg, s.c.) also improved motor coordination and exploratory behavior significantly as compared to naïve sham operated and GCSF (10 μg/kg, s.c.) groups (p<0.05). Improvement in memory by GCSF (35 and 70 μg/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 μg/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 Aβ-induced Alzheimer's disease model in rats.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Prakash
authors.forename: Bikash
authors.initials: B
authors.lastname: Medhi
authors.forename: Kanwaljit
authors.initials: K
authors.lastname: Chopra
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects*; D017931:DNA Primers; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D008297:Male; D008568:Memory / Q000187:drug effects*; D009573:Nitrites / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D017931:DNA Primers; D009573:Nitrites; D016179:Granulocyte Colony-Stimulating Factor; D000110:Acetylcholinesterase
keywords: AD; Alzheimer's disease; Aβ(1–42); BDNF; CAT; DG; EDTA; EPO; GCSF; GSH; HSCs; ICV; N-methyl-d-aspartate; NBT; NMDA; SOD; TBA; TLT; amyloid-beta (1–42); brain-derived neurotrophic factors; catalase; dentate gyrus; erythropoietin; ethylenediamine tetrachloroacetic acid; granulocyte colony-stimulating factor; intracerebroventricular; mAChR; muscarinic receptor; nAChR; nicotinic receptor; nitro blue tetrazolium; reduced glutathione; superoxide dismutase; thiobarbituric acid; transfer latency time