Abstract:【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 gyrus respectively were 178.7 ± 11.9 and 220.9 ± 16.7;The OD value (× 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 0.05)【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 hippocampal formation

inhibit neurodegeneration of in the septo-hippocampal cholinergic system before SAMP-8 mice appears senescence.