褪黑素对不同年龄SAM-P8小鼠学习记忆相关脑区的影响

Effects of Melatonin on Brain Regions Associated with Learning and Memory of SAMP-8 Mouse of Different Ages

【目的】研究褪黑素的短期干预对不同年龄SAM-P8脑内膈隔-海马胆碱能系统和海马结构退变的影响。【方法】选用SAM-P8鼠36只,分为中年低、高浓度治疗组(ME1G、ME2G),老年低、高浓度治疗组(AE1G、AE2G)及其相应的对照组ACG、MCG),共6组。中年、老年治疗组分别于小鼠4月龄、7月龄时每日皮下注射褪黑素(5 mg或10 mg/kg)30 d。对照组注射相同剂量的生理盐水,给药结束后继续饲养到11月龄,采用跳台试验测试其学习及记忆能力,取脑进行海马结构尼氏染色和Ach E酶组织化学染色,基底前脑Ch AT免疫组化染色。【结果】中年对照组和中年高浓度治疗组结果如下:跳台实验逃避潜伏期分别是(41.9±8.9)s和(28.9±7.8)s;5 min内错误次数分别是6.1±1.6和3.3±0.9;24 h后逃避潜伏期分别是(11.5±2.1)s和(6.4±2.2)s,P<0.05;海马CA1区锥体细胞层神经元数分别是(88.1±10.6)个和(132.5±17.2)个;齿状回颗粒细胞数分别是(178.7±11.9)个和(220.9±16.7)个;海马CA1区胆碱能纤维OD值(×103)分别是410±34和471±44;齿状回胆碱能纤维分别是364±34和416±34;膈内侧核胆碱能神经元数分别是48.4±7.1和66.2±9.7;斜角带垂直支胆碱能神经元数分别是73.9±11.1和93.7±11.3。中年高浓度治疗组的上述指标与中年对照组比较有明显差异(P<0.01或P<0.05)。其余治疗组的上述指标与相应对照组比较差异不明显(P>0.05)。【结论】MT对SAM-P8小鼠治疗作用存在年龄差异,衰老前的褪黑素早期干预可明显改善SAM-P8小鼠的学习能力,减少海马结构神经元丢失,抑制隔-海马胆碱能系统的退变。

[Objective] To study the effects of melatonin in short-term treatmenton the septohippocampal cholinergic system and hippocampal formation in SAMP-8 mouse of different ages. [Methods] 36 SAM-P8 mice were randomly divided into middle-aged high or low concentration treatment group,aging high or low concentration treatment group and related control group （n = 6 for each group）. The 4 months old SAMP8 mice （middle-aged treatment group） were injected subcutaneously with melatonin （5 mg/kg or 10 mg/kg） for 30 d. Similar treatments were performed in the 7 months old mice （aging treatment group）. When the animals were complete 11 months old,a series of tests were performed. The step-down test were used to assess cognitive performance. The hippocampal formation of mice were stained by the Ache enzyme histochemistry and cresyl viollet.The basal forebrain of mice were stained by the immunohistochemistry of CHAT. [ Results ] Data of related control group and middle-aged high concentration treatment group as following： The escape latency in the step-down test respectively were （41.9± 8.9）s and （28.9 ± 7.8）s;The numbers of error within 5 min respectively were（6.1 ± 1.6）time and（3.3 ~ 0.9）time; The escape latency after 24 h respectively were （11.5 ±2.1 ）s and（6.4 ± 2.2）s; The number of pyramidal neurons in the hippocampal CA1 area respectively were 88.1 ± 10.6 and132.5 ± 17.3;The number of granule cell layer in dentate gyms respectively were 178.7 ~ 11.9 and 220.9 ± 16.7;The OD value （x 103） for number of cholinergic fiber in the hippocampal CA1 area respectively were 410 ＋ 34 and 471 ＋ 44;The number of cholinergic fibers in dentate gyrus respectively were 364 ± 34 and 416 ± 34 ;The number of cholinergic neurons in the medial septum respectively were 48.4 ± 7.1and 66.2 ± 9.7;The number of granule cell layer in vertical limb of diagonal band respectively were 73.9 ±11.1 and 93.7 ± 11.3. The middle-aged high concentration treatment group was significant differences compared with the control group above-mentioned data （P 〈 0.01 or P 〈 0.05 ）.Data of other treatment group was no significant differences compared with related control group （P 〉 0.05） [Conclusion]Our results indicate that the protective effects of melatonin on neurodegeneration of SAMP8 mice are age dependent.The short term treatment of melatonin obviously improve the capability of learning, decrease neuronal loss in hippoeampal formation, inhibit neurodegeneration of in the septo-hippocampal cholinergic system before SAMP-8 mice appears senescence.