| Objective:To observe the effects of curcumin and Rapamycin on the ability of learning and memory, the expression of Aβ and neuronal autophagy in the hippocampus of AD rats models, and to explore the neuroprotective effects of curcumin and its possible mechanism.Methods:A total of80healthy7month-old female Sprague-Dawley rats were randomly assigned to four groups:Control group, AD model group, Curcumin group, Rapamycin group. Rats of the AD model group, Curcumin group and Rapamycin group received operation to build the AD rats model, by which Aβ1-42was injected into the CA1region of the hippocampus in them. The rats of Control group were injected with the same volume of physiological saline instead by the same method. From the fifth day before operation, rats in the Curcumin group and Rapamycin group were given a corresponding dose of curcumin and rapamycin through intraperitoneal injection till the end of the experiment, the21st day after operation. And the rats of Control group and AD model group received intraperitoneal injection with the physiological saline instead during the same period. Morris Water Maze was used to test the ability of learning and memory of rats. Hematoxylin-eosin staining was used to observe the morphology of neurons in the hippocampus. Immunohistochemical staining was used to detect the expression of Aβ1-40in hippocampus. The transmission electron microscope was used to observe the autophagosome in the neuron of CA1region of hippocampus. Western Blot was used to detect the expression of Beclin-1and LC3-Ⅱ in hippocampus.Results:1.Morris water maze test results:In the place navigation, compared with Control group, the escape latency in AD model group is significantly longer(P<0.01),while the escape latency in Curcumin group and Rapamycin group was shorter than AD model group(P<0.05), and there was no significant difference between Curcumin group and Rapamycin group(P>0.05); In the spatial probe, compared with Control group, the ratio of swimming time (path) in the quadrant located with previous platform to the total swimming time(path) in AD model group decresed significantly(P<0.01), while the ratio of swimming time (path) in Curcumin group and Rapamycin group was upregulated than AD model group(P<0.05), and there was no significant difference between Curcumin group and Rapamycin group(P>0.05).2.HE staining:Neurons in hippocampus of rats in Control group shows a normal morphology. Apoptosis was evident in in AD group, with the loss of normal neurons; the morphology of neurons in hippocampus tended to be normal in the Curcumin group and Rapamycin group.3.1mmunohistochemical staining:Compared with Control group, the expression of Aβ1-40in hippocampus increased significantly in AD model groups(P<0.01), while the curcumin and rapamycin downregulated the expression of Aβ1-40(P<0.05), and there was no significant difference between Curcumin group and Rapamycin group(P>0.05). 4.Transmission electron microscope:The accumulation of autophagosome were evident in neurons of CA1region in hippocampus of AD model rats, accompanied with swelling mitochondrion, fluffy endoplasmic reticulum, and fuzzy nuclear membrane; while there was only a few of autophagosome surrounded by the nucleus in other three groups, in which nucleus and Organelles remained a normal structure.5.Western Blot:Compared with AD model groups, the expression of Beclin-land LC3-Ⅱin hippocampus were upregulated significantly in Control group, Curcumin group and Rapamycin group(P<0.05), and there was no significant difference during the later three groups(P>0.05).Conclusions:1. Curcumin and rapamycin can alleviate the impairments of learning and memory abilities in AD model rats, attenuate the neuronal injury in hippocampus, and show a neuroprotective effect in AD model rats.2.To induce the neuronal autophagy, upregulate the expression of Beclin-1and LC3-Ⅱ, and alleviate the burden of Aβ shows a possible way that curcumin and rapamycin play as an neuroprotective effect. |
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