Effect Of Declining Function Of Pineal On Alzheimer's Disease And Its Mechanism

OBJECTIVES: To investigate effects of decreased melatonin (MT) secreation caused by declining function of pineal on Alzheimer抯 disease (AD). MEHTODS: (1).After tested by Y-type maze, the rats with normal study ablity were randomly divided into two groups including the experimental group with pinealectomy and the control with sham operation, however, the rats with dysfunction of learning were eliminated. AS soon as the rats both of experiment and control were fed for 40 days, Y-type maze test was performed once more, and the simples of brain were histochemical studied by acetycholinesterase (AChE) and by SABC method for neuronal nitric oxide synthase (nNOS). (2). The rats were divided into three groups randomly after tested by Y-type maze and those with dysfunction of learning were eliminated. The experimental group was perfonned by pinealectomy, the control was made sham operation and the blank control was untreated. The rats were tested again by Y-type maze after fed for forty days and the brain tissues were stained by Nissl and I-IF method respectively. The neuromc apoptosis in the hippocampus were examined with terminal deoxynucleotidyl-transferase mediated d-UTP-biotin nick end labeling (TUNEL). Bax and Bcl-2 expression were stuided by SABC method. Astrocytes were marked by glial fibrillary acidic protein (GFAP) with SP method. (3).The rats with normal study ablity were randomly divided into two groups including the experimental group with pinealectomy and the control with sham operation. The apoptotic cells in the central neurons were examined with TUNEL method and the related gene Bax, Bcl-2 and c-fos expression were studied by SABC method. The concentration of malondialdehyde (MDA) of lipid peroxidation prodution was made using the microassay. (4). The SD rats were divided into two groups randomly. Experimented group was treated by pinealectomy and the control was performed by sham operation. incubated amyloid P protein 1-40 (A13) [10 .ig (10 j.tg/.tl) I was injected into the rats right hippocampus at the 40th day after pinealectomy or sham operation.The pathological changes of neurons were examined with toluidine blue, haematoxylin-eosin(HE), improved congn red staining and TUNEL method at the 7th day after injection. The apoptotic cells were examined with TU7NIEL method and the related genes Bax and BcI-2 expression by SABC method. GFAP with SP method were studied. RESULTS: (1).The rats of pinealectomy showed decreased learning ability, the AChE-positive fibers density was more significant decreased than those of the control rats in 11 IV layers of motor and somatosensory cortx, in radiative, lacunaria and molecular layers of CA1,CA2,3 areas, and in lamina multiformls of dentate gyms, but nNOS- positive cell in neocortex and SM-DB were more than that of control rats. There is no difference between the experimental and the control rats in nNOS-positive cell quantity of corpus striatus and hippocampus. (2). The ability of learning and memory of the rats in experimental group was worse than that of the control ones, apoptotic cells in the hippocampus were more, but there was not differenct between Bax and Bcl-2 protein expression. The (iFAP-positive cells in hippocumpus were obviously less. (3). Although the apoptotic cells in diagonal tractus ?septal area were more and c-fos expression in the central nervous system of the rats peformed by pinealectomy were obviously less, there was not differenct Bax and Bcl-2 protein expression between the experimental and...