Leptin Attenuates Aβ1-42-Induced Detrimental Effects on Spatial Memory and Hippocampal L-LTP in Rats

【作者】 仝嘉庆； 张军； 郝明； 杨菊； 祁金顺；

【机构】 山西医科大学生理学系教育部重点实验室；

【摘要】 Amyloid beta protein(Aβ)aggregated in the brain of patients with Alzheimer’s disease(AD)has been proved to be crucially involved in the memory loss and cognition impairments.It is reported recently that Leptin,a 16k D satiety signal protein,is expressed in central nervous system,and has the ability to modulate hippocampal synaptic plasticity.Thus the present study investigated the probable neuroprotective effects of leptin against Aβ1-42 in rats using behavioral and electrophysiological techniques.The results showed that:(1)daily introcerebroventricular injection with 1ug leptin for 10 days attenuated Aβ1-42 induced impairments in spatial learning and memory in Morris water maze task.The rats in leptin+Aβ1-42 treatment group spent less time in finding the hidden platform than those in Aβ1-42alone group on the 2nd-5th training days,but spent more swimming time in target area in probe test.No difference in visual platform test and swimming velocity was found between the two groups.(2)leptin administration reversed Aβ1-42-induced suppression of hippocampal late-phase long term potentiation(L-LTP)in the CA1 region in vivo.The average ampllitude of f EPSPs in leptin+Aβ1-42 treatment group was 1.518±0.374(relative to base line),while the ampllitude of f EPSPs in Aβ1-42 alone group was1.151±0.190 3h after high frequency stimulation.These results suggest that leptin application might be a promising strategy in the treatment of degenerative disease in central nervous system such as AD.更多还原

【Abstract】 Amyloid beta protein(Aβ) aggregated in the brain of patients with Alzheimer’s disease(AD) has been proved to be crucially involved in the memory loss and cognition impairments.It is reported recently that Leptin,a 16 k D satiety signal protein,is expressed in central nervous system,and has the ability to modulate hippocampal synaptic plasticity.Thus the present study investigated the probable neuroprotective effects of leptin against Aβ1-42 in rats using behavioral and electrophysiological techniques.The results showed that:(1) daily introcerebroventricular injection with 1ug leptin for 10 days attenuated Aβ1-42 induced impairments in spatial learning and memory in Morris water maze task.The rats in leptin+Aβ1-42 treatment group spent less time in finding the hidden platform than those in Aβ1-42 alone group on the 2nd-5th training days,but spent more swimming time in target area in probe test.No difference in visual platform test and swimming velocity was found between the two groups.(2) leptin administration reversed Aβ1-42-induced suppression of hippocampal late-phase long term potentiation(L-LTP) in the CA1 region in vivo.The average ampllitude of f EPSPs in leptin+Aβ1-42 treatment group was 1.518±0.374(relative to base line),while the ampllitude of f EPSPs in Aβ1-42 alone group was 1.151±0.190 3h after high frequency stimulation.These results suggest that leptin application might be a promising strategy in the treatment of degenerative disease in central nervous system such as AD.更多还原