Development of model animals and cells for neuronal disease

The senescence accelerated mouse(SAM)is known as a murine model of aging.SAM consists of senescence accelerated-prone mouse(SAMP)and senescence accelerated-resistant mouse(SAMR)。Previously，we reported that SAMP8 and SAMP10exhibit age-related learning impairments.In this study，we investigated the changes in emotional behavior and in neurotansmitter receptor in SAMP10，and the effect of onion extract on learning ability in Morris‘s water maze test.1)SAMP10at8months showed an increases of immobility in a forced swimming test compared with SAMR1。Treatment with desipramine(25 mg/kg，I.p.，3days)in SAMP10caused a decrease in immobility.2)In the cortex from SAMP1O，[I.D13ii D1H]quinpirol binding to D2/D3dopamine receptors increased significantly.In the hippocampus from SAMP10，[I D 13 I D 1H]hydroxy DPAT binding to 5-HT I D 11 A I D 1 receptors increased.3)In Morris‘s water maze task，in a control strain of SAMR 1 at 8 months，the escape latency and path length decreased with increasing trial days，in contrast，the escape latency and path length did not change in SAMP 8.Treatment with onion extract(5ml/kg，p.o.，2months)in SAMP8improved the learning and memory in the task.4)In the control rats pretreated with the vehicle，transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA1region was observed7days after reperfusion.Pretreatment with glial cell line-derived neurotrophic factor(1µg)，which was directly microinjected into the right hippocampal CA1region，gave significant protection against the neuronal death.CV-159(A Dihydropyridine Derivative)that blocks the L-type Ca I D12+ii D1 channel and inhibits the calmodulin-dependent pathway.CV-159 gave protection against delayed neuronal death in the CA1 region after 15-min transient forebrain ischemia.

The senescence accelerated mouse (SAM) is known as a murine model of aging. SAM consists of senescence accelerated-prone mouse (SAMP) and senescence accelerated-resistant mouse (SAMR). Previously, we reported that SAMP8 and SAMP10 exhibit age-related learning impairments . In this study, we investigated the changes in emotional behavior and in neurotansmitter receptor in SAMP10, and the effect of onion extract on learning ability in Morris's water maze test.1) SAMP10 at 8 months showed an increases of immobility in a forced swimming test compared with SAMR1. Treatment with desipramine (25 mg/kg, I.p., 3 days) in SAMP10 caused a decrease in immobility.2) In the cortex from SAMP1O, [ィイD13ィエD1H]quinpirol binding to D2/D3 dopamine receptors increased significantly. In the hippocampus from SAMP10, [ィイD13ィエD1H]hydroxy DPAT binding to 5-HTィイD11AィエD1 receptors increased.3) In Morris's water maze task, in a control strain of SAMR1 at 8 months, the escape latency and path length decreased with increasing trial days, in contrast, the escape latency and path length did not change in SAMP8. Treatment with onion extract (5 ml/kg, p.o., 2 months) in SAMP8 improved the learning and memory in the task.4) In the control rats pretreated with the vehicle, transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA 1 region was observed 7 days after reperfusion. Pretreatment with glial cell line-derived neurotrophic factor (1 μg), which was directly microinjected into the right hippocampal CA1 region, gave significant protection against the neuronal death. CV-159 (a dihydropyridine derivative) that blocks the L-type CaィイD12+ィエD1 channel and inhibits the calmodulin-dependent pathway. CV-159 gave protection against delayed neuronal death in the CA1 region after 15-min transient forebrain ischemia.