Studies on the Machanism of Memory Disturbances in Senescence-Accelerated Mouse and the Application to Screening of Nootropics

衰老加速小鼠（SAM）是一种加速衰老的小鼠模型。与对照组（SAMR 1）相比，在P8品系（SAMP 8）中也观察到随年龄增长的记忆障碍。为建立筛选抗衰老和改善记忆的有效药物的方法学，我们采用SAMP 8软件研究了中药对记忆障碍的影响。以500 mg/kg/d剂量对4月龄小鼠口服具有改善外周微循环障碍作用的东方药物--檀金的甲醇提取物，每周5次，连续3周。Morris水迷宫法检测大鼠空间识别能力。与载体对照相比，提取物改善了空间识别。此外，该提取物不影响运动活动，但缩短了水浴中的不动时间。因此，檀金的甲醇提取物含有改善大脑功能的活性化学物质。然后，我们测量了用提取物处理的SAMP 8局部脑中[^3H]MK-801（与NMDA受体）和[^3H]N^G-硝基精氨酸（[^3H]NNA）（与一氧化氮合酶）的结合。该处理增加了大脑皮层中的[^3H]MK-801结合和脑干中的[^3H]NNA结合，表明Tan-jin对脑中突触神经传递和神经递质受体介导的跨膜信号传导有效。我们仍在研究以下几点：1）活性化学物质的鉴定，2）作用的细胞和分子机制，3）精神和智力障碍患者的临床应用。提示SAMP 8是研究增龄性记忆障碍机制和筛选治疗药物的理想动物模型。

Senescence-accelerated mouse (SAM) has been esstablihed as a murine model showing accelerating aging. Memory impairment with aging is also observed in P8 strain (SAMP8) in contrast to the control (SAMR1). To establish the methodology screening effective drugs with anti-aging and memory improvement, we investigated effects of herbs on memory disturbance using SAMP8. The methanol extract from Tan-jin, an oriental medicine with improving effects on peripheral microcirculation disturbances at 500 mg/kg/day was orally administrated five time a week for 3 weeks into 4-month-old mice. Spatial recognition ability was evaluated by the Morris water maze methods. The extract ameliorated spatial recognition compared to the vehicle control. In addition, the extract did not affect locomotor activity but shortened the immobility time in the water bath. Therefore the methanol extract from Tan-jin contains active chemicals improving the brain functions. We then measured [^3H]MK-801 binding (to NMDA receptors) and [^3H]N^G-nitro-arginine ([^3H]NNA) binding (to nitric oxide synthase) in regional brains of SAMP8 treated with the extract. The treatment increased the [^3H]MK-801 binding in cerebral cortex and [^3H]NNA binding in brain stem, suggesting that Tan-jin is effective on synaptic neurotransmission and neurotransmittor receptor-mediated transmembrane signaling in the brain. We still are investigating following points : 1) identification of active chemicals, 2) the cellular and moleular mechanism of the action, 3) clinical application to patients with mental and intellectual disturbances. We can propose that SAMP8 is an useful animal model studying the mechanism of age-related memory impairment and screening the therapeutic drugs.