A Study Of The Effect Of RhG-CSF On Alzheimer's Disease (AD) Induced By Aβ1-42 In Rat

Objective Alzheimer's disease(AD)affects more than 12 million patients worldwide,and it accounts for most of the dementia diagnosed after the age of 60. The disease is clinically manifested by a global decline of cognitive function that progresses slowly.The characteristic features of AD brains are the formation of neurofibrillary tangles and the presence of senile plaques,the neurotoxicity of which are believed to be responsible for the neuronal loss and the degeneration of the cholinergic system in AD patients.No treatments can stop AD today.Most of the current clinical treatments for AD are largely symptomatic,including the use of acetylcholinesterase inhibitors to improve cognitive ability and psychotropic drugs to modify patient behaviors.Treatments that focus on delaying the onset of symptoms and slowing the rate of disease progression are also being used.These strategies enhance the functions of the survival neuronal cells,and they include the uses of(a) tacrine,the first Food and Drug Administration approved drug for AD therapy;(b) memantine,an N-methyl-D-tspartate antagonist;and(c)antioxidants such as vitamin E,Other likely promising therapies for AD include antiamyloid immunotherapy, amyloid vaccination,and the use of secretase inhibitors that prevent the formation of Aβand neurofibrillary tangles.However,these therapies could all cause side effects and,consequend clinical problems.G-CSF is a hematopoietic growth factor named for its role in the proliferation and differentiation of cells of the myeloic lineage. Administration of G-CSF mobilized hematopoietic stem cells(HSCs)from the bone marrow into the peripheral blood,The peripheral blood-derived HSCs have been used in place of bone marrow cells in transplantation for the regeneration of nonhematopoietic tissues such as skeletal muscle and the heart.This study is to investigate the effects of rhG-CSF on the cognition disorders and antiapoptosis of Alzeimer's Disease(AD)induced by Aβ1-42 in rat.Methods(1)The experimental model of animal:Male Wistar rats with normal cognition,Aβ1-42 was injected into bilateral hippocampus.(2)The experiment to treat AD induced by Aβ1-42 in rat:84 male rats were randomly divided into three groups:Aβgroup,rhG-CSF group and control group.Aβ1-42 5ul(10ug)was injected into bilateral hippocampus in Aβgroup and rhG-CSF group,0.9%NS 5ul was injected into bilateral hippocampus in control group.Rats in rhG-CSF group were given rhG-CSF 50 ug/(kg·d)subcutaeneuslly one time per day for 5 days,Aβgroup were given normal saline.Morris water maze test was done on the 7th,14th,21th,and 28th day after administration,record the escaping latency and the percentage of swimming distance in the target quadrant of each mouse.After each test,execute the mice,make paraffin slice up and then obeserve the expression of caspase-3 by immunohistochemistry method respectively.Take photoes of all the pictures and count the immunity positive cells.SPSS11.0 for Windows was used to analyze the data.All the data were expressed as means±S.D.(x±s)and analyzed by one-way anova。P＜0.05 was taken as the statistical standard.At the end of experiment,the rat were decapitated,then brain was separated for examination of configuration and super microstructure by optic miscroscope and expression of caspase-3 protein by immunohistochemistry method.Result(1)Morris water maze test result:Aβgroup compared with control group,the avoiding latent period extended,the percentage of time in the platform quadrant and the time of crossing platform obviously decreased,P＜0.01;Compared with Aβgroup,the avoiding latent period of rhG-CSF group shorten,the percentage of time in the platform quadrant and the time of crossing platform obviously increased, P＜0.05.Spatial probe test result Compared with Aβgroup,the percentage of swimming distances in the target quadrant of rhG-CSF group increased.(P＜0.05);(2) Observe the expression of caspase-3 in hippocampus by immunohistochemical method.After injected Aβ1-42,the positive rate of caspase-3 protein in rat's hippocampus of Aβgroup significantly increased.Compared with Aβgroup,the positive rate of caspase-3 protein of rhG-CSF group significantly decreased,P＜0.05.Conclusion(1)rhG-CSF can improve the cognition disorders of Alzeimer's Disease(AD)induced by Aβ1-42 in rat,and delay the decline of its learning and memory ability to some extent.(2)rhG-CSF can decrease the caspase-3 immunity positive cells in the hippocampus of rat induced by Aβ1-42 to some extent.