Effects Of Curcumin On Neuronal Endoplasmic Reticulum Stress In AD Rats Models

OBJECTIVE:To observe the effects of curcumin on the ability of learning and memory, the apoptosis, the expression of Aβ, endoplasmic reticulum stress and endoplasmic reticulum stress induced apoptosis in the hippocampus CA1region of AD rats models, and to explore the neuroprotective effects of curcumin and its possible mechanism.METHODES:A total of120healthy7month-old male Sprague-Dawley rats were randomly assigned to three groups:Control group, AD model group, Curcumin group. Rats of the AD model group, Curcumin group received operation to build the AD rats model, by which Aβ1-42was injected into the CA1region of the hippocampus. 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 of the Curcumin group group were given a corresponding dose of curcumin through intraperitoneal injection till the end of the experiment, the3rd,7th,14th,21st 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 before ended in the21st day. Then, Hematoxylin-eosin staining was used to observe the morphology of neurons in the CA1region of hippocampus.TUNEL staining was used to observe the apoptosis of neurons in the CA1region of hippocampus. Immunohistochemical staining was used to detect the expression of Aβ1-40in the CA1region of hippocampus. Immunohistochemical staining was also used to detect the expression of GRP78, the maker of endoplasmic reticulum stress, and caspase-12, the maker of endoplasmic reticulum stress induced apoptosis, in the CA1region of 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 was shorter than AD model 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 was upregulated compared with AD.2. HE staining:Neurons in hippocampus of rats in Control group shows a normal morphology. Apoptosis was evident in AD group, with the loss of normal neurons; the morphology of neurons in hippocampus tended to be normal in the Curcumin group.3. TUNEL staining:In hippocampus CA1region of rats, the number of TUNEL positive cells of AD group and Curcumin group was higher than Control group at all time points(P<0.05). And curcumin group’s was lower than AD group at all time points except for the3rd day(P<0.05).4. Expression of Aβ1-40:In hippocampus CA1region of rats,the expression of Aβ1-40of AD group and Curcumin group was higher than Control group at all time points(P<0.05). And curcuin group’s was lower than AD group at all time points except for the3rd day(P<0.05).5. Expression of GRP78:In hippocampus CA1region of rats, the expression of GRP78of AD group and Curcumin group was higher than Control group at all time points(P<0.05). And curcuin group’s was lower than AD group at14th and21st day.(P<0.05).6. Expression of caspase-12:In hippocampus CA1region of rats,the expression of caspase-12of AD group and Curcumin group was higher than Control group at all time points(P<0.05). And curcuin group’s was lower than AD group at14th and21st day (P<0.05).CONCLUSION:1. Curcumin can alleviate the impairments of learning and memory abilities in AD model rats, attenuate the neuron loss and lighten the load of Aβ in hippocampus of AD model rats;2. Curcumin may play an neuroprotective effect on pathologenesis of AD by alleviating endoplasmic reticulum stress and endoplasmic reticulum stress induced apoptosis.