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

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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.