Influence of D-galactose on rat spatial learning memory behavior as well as cerebral hippocampal electrophysiology and synaptic morphology
- VernacularTitle:D-半乳糖对大鼠空间学习记忆行为与脑海马结构电生理以及突触形态学的影响
- Author:
Shujuan YUAN
;
Zhixiong ZHANG
;
Dingzong WU
;
Hong QIU
;
Wenlong DING
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(37):172-175
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Learning memory disorder is one of the major manifestations of aging. The model of aging induced by D-galactose is a commonly used animal model in recent years, and long-term D-galactose exposure may cause nerve cell morphological changes in animals.OBJETCIVE: To observe spatial learning memory behavior during Dgalactose-induced aging process in order to further explore in vivo evoked long-term potentiation in hippocampus dentate gyrus and synaptic morphological changes in hippocampal CA3 region.DESIGN: Randomized controlled observation.SETTING: Anatomical Teaching and Research Secti , Shanghai Second Medical University; Department of Physiology, Shanghai Traditional Chinese Medicine University.MATERIALS: The experiment was carried out at the Physiological Laboratory of Shanghai Traditional Chinese Medicine University between August 2000 and April 2001. Totally 22 male Wistar rats of 3-month birth age were included and randomized into normal group and D-galactose group with 11 rats in each group. D-galactose was produced by Shanghai No. 2 Chemical Reagent Factory, Morris water maze was home-made by the Institute of Geriatrics, Shanghai Traditional Chinese Medicine university.METHODS: Rats were subjected to hypodermic injection of 1 mL normal saline every day in normal group, or D-galactose of 800 mg/kg daily for 6consecutive weeks in D-galactose group. Rat spatial learning memory behavior was assessed by the latency of Morris water maze; hippocampal dentate gyrus community potentials evoked by monopulse stimulation on perforating fibers were recordedin vivo; meanwhile, the amplitude of monopulse evoked potentials was determined before and after high frequency stimulation, with the amplitude before high frequency stimulation taken as baseline. Transmission electromicroscope was applied in combination with imaging analysis to observe synaptic morphology and structure in rat hippocampal CA3 region. Water labyrinth latency was compared using the variance analysis of repetitive survey design, t-test was used to compare the differences of peak potential latency of community potentials at various time points after long-term potentiation. Moreover, inducing rate of longterm potentiation was compared by χ2-test, XY-540 type biological imaging processing system was used to analyze electromicroscopic pictures, and all available data were analyzed with t-test.MAN OUTCOME MEASURES: [1] Main outcomes: Changes of Morris water maze latency, as well as inducing rate of long-term potentiation and community potentials. [2] Secondary outcomes: Synaptic morphological and structural changes in hippocampal CA3 region.RESULTS: Totally 22 rats were enrolled in this study, with no one lost during water labyrinth test, but one rat in both normal group and D-galactose group died during electrophysiological experiment. Finally 3 rats were randomly selected from each group for electromicroscopic observation. [1]Comparison of the latency for Morris water maze: In contrast with that of normal group, latency for seeking submarine platform was obviously prolonged in D-galactose group [(14.77±10.10), (51.36±12.45) s, P ＜ 0.05].[2] Comparison of evoked potential in hippocampus dentate before high frequency stimulation: The two groups did not obviously differ in community potential amplitude and community potential latency [(1.05±0.47),(0.91±0.41) mV; (5.46±2.09), (5.38±2.26) ms; P ＞ 0.05]. [3] Inducing rate of long-term potentiation in hippocampal dentate gyrus: Compared to that of normal group, inducing rate in D-galactose group obviously reduced after high frequency stimulation (80%, 20%, χ2=7.20, P ＜ 0.01). [4] Comparison of community potential ratio at different time points after high frequency stimulation: Compared to that of normal group, it was notably reduced in D-galactose group at post-stimulation 20, 30, 60 minutes, respectively (1.104±0.196, 0.919±0.162; 1.354±0.212, 0.999±0.219; 1.236±0.174,0.875±0.311; P ＜ 0.05). [5] Comparison of synaptic struc tural parameters in hippocampal CA3 region: Compared to that of normal group, postsynaptic dense bodies became thickened in hippocampal CA3 region of D-galactose group [(40.60±18.26), (26.35±8.15) nm, P ＜ 0.05], the synapse gap increased [(17.69±6.28), (26.95±5.67) nm, P ＜ 0.05] while synaptic active zone was shortened [(265.13±76.50), (229.13±90.68) nm, P ＜ 0.05].CONCLUSION: Hypodermic injection of D-galactose does harm to rat spatial learning memory by reducing the long-term potentiation, inducing rate in rat hippocampal dentate gyrus, attenuating the increase of long-term potentiation-evoked potential amplitude, and even remarkably changing the synaptic ultrastructure in rat hippocampal CA3 region. It suggests that Dgalactose inhibits the long-term potentiation at hippocampal dentate gyrus and affects synaptic structure in hippocampal CA3 region, which is considered as the basis of spatial learning memory behavioral disorder.
