| Object:To investigate the effect of chronic intermittent hypoxia(CIH) on the cognitive function in Parkinson's disease miceMethods: Forty-four male C57BL/6 mice at six weeks were randomly divided into control group, Paraquat (PQ) group, CIH group and PQ+CIH group. Body weight of mice were determined at the beginning and the end of the experiment. Behavioral tests of mice were determined by the pole test and open field Learning and memory function were evaluated by Y-type maze and step-down test; Acetylcholinesterase(Ach E) activity and Acetylcholine (Ach) levels in hippocampus of mice were detected by colorimetric method; Synaptophysin(SYN) expression in the hippocampus were observed by immunohistochemistry and The grey number of SYN in the hippocampus of mice; HE staining, Nissl staining and electron microscope studied the amount, morphology and ultrastructure in hippocampus of mice.Results: 1.No statistical significance were found in body weight of mice among of each group at the beginning and the end of the experiment(P>0.05).2.The scores of pole test: No statistical significance were found by pole test in each group at the beginning of the experiment (P>0.05)；Compared with the control group, the scores were decreased in the other 3 groups at the end of the experiment (P<0.05); Compared with the CIH group, the scores were decreased in PQ group and PQ+CIH group (P<0.05); Compared with the PQ group, the scores were decreased in PQ+CIH group (P<0.05).3.The scores of the spontaneous motor activity: No statistical significance were found by spontaneous motor activity in the open field in each group at the beginning of the experiment (P>0.05); At the end of the experiment, compared with control group, the ambulation and the rearing were decreased in the other 3 groups (P<0.05); Compared with CIH group, the scores were significantly decreased in PQ group and PQ+CIH group (P<0.05); Compared with PQ group, the scores were significantly decreased in PQ+ CIH group (P<0.05).4.The performance records of Y-type maze:Total reaction time(TRT) and Error number(EN) of learning showed respectively 68.73±11.63,79.37±7.16,81.46±10.29,97.27±11.49 and 2.45±1.51,4.09±1.87, 4.18±0.98,5.55±1.03 in control group, PQ group, CIH group and CIH+PQ group by Y-type maze. TRT and EN of memorizing showed respectively 59.27±7.19,73.36±6.56,76.55±8.93,96.64±13.10 and 1.73±1.01,3.09±1.14,3.55±1.37,5.36±1.29 in control group, PQ group, CIH group and CIH+PQ group by Y-type maze. Compared with control group, the learning and memorizing were increased in the other groups by Y-type maze(P<0.05), especially significant in PQ+CIH group(P<0.01). Compared with PQ and CIH group, the records were also increased in PQ+CIH group (P<0.05). No significant difference was found in learning and memorizing within the PQ group and CIH group (P>0.05).5.The performance record of step-down test: Reaction time(RT) and EN of learning showed respectively 3.09±0.70,4.45±1.50,4.64±1.36,6.09±1.81, and 2.64±0.81,3.73±0.90,3.84±1.39,5.09±1.51,and RT and EN of memorizing showed respectively 3.00±1.00,4.18±1.54,4.29±1.55,5.64±1.12 and 2.45±0.93, 3.82±0.87,4.00±1.84,5.45±1.92 in each group by step-down test. Compared with control group, the learning and memorizing were increased in the other groups by Y-type maze (P<0.05), especially significant in PQ+CIH group (P<0.01). Compared with PQ and CIH group, the records were also increased in PQ+CIH group (P<0.05). No significant difference was found within the PQ group and CIH group (P>0.05).6. Acetyl cholinesterase (Ach E) activity and Acetylcholine (Ach) levels in hippocampus: Levels in hippocampus showed respectively 8.04±0.37,7.62±0.53,7.63±0.45,7.20±0.49 and 3.13±0.17,2.95±0.17, 2.92±0.14,2.73±0.26 in each group by colorimetric method. Compared with control group, the Ach E activity and Ach levels were decreased in the other groups (P<0.05), especially significant in PQ+CIH group (P<0.01). Compared with PQ and CIH group, the level were also decreased in PQ+CIH group (P<0.05). No significant difference was found within the PQ group and CIH group (P>0.05).7.The grey number of SYN in hippocampus:The grey number showed respectively 129.61±1.84, 132.39±2.96,132.58±3.08,135.08±2.62 in each group. Compared with control group, The grey number of SYN were increased in the other groups (P<0.05), especially significant in PQ+CIH group (P<0.01). Compared with PQ and CIH group, the number were also increased in PQ+CIH group (P<0.05). No significant difference was found within the PQ group and CIH group (P>0.05).8. The appearance of Nerve cell of hippocampus by HE staining and Nissl staining: Neurons in the hippocampus of control group showed even of density and distribution, distinct of nucleus texture and nissl's body. Most neurons architecture disaggregation, nissl's body decrease and even vanish in the other groups, especially appeared in PQ+CIH group. Cell counts showed respectively 264.91±12.77, 239.73±14.79,244.73±13.35,225.36±11.41 in each group by Nissl staining.Compared with control group, The Cell counts were decreased in the other groups (P<0.05), especially significant in PQ+CIH group (P<0.01). No significant difference was found within the PQ group and CIH group (P>0.05). 9.The appearance of Nerve cell of hippocampus by Electron microscope: Neurons in the hippocampus of control group showed abundant Organelles, even chromatin and clear Nucleoli. Organelles decrease, nuclei irregular and lysosomes granules increased in the other 3 groups.Conclusions:CIH increased the degree of cognitive impaired in PQ-induced PD model mice. It may be related with the decrease of the Ach level, the Ach E activity, the synapse and neuron in hippocampus. |
PDF Full Text Request