摘要：The pathological significance of amyloid-β 1–42 (Aβ 1–42 ) dynamics is poorly understood in the brain extracellular compartment. Here we test which of the concentration or the retention is critical for Aβ 1–42 toxicity after injection of equal dose into dentate granule cell layer of freely moving rats. The toxicity of Aβ 1–42 (25 µM) was compared between injections at the rate of 0.25 µL/min for 4 min (fast injection) and 0.025 µL/min for 40 min (slow injection). Dentate gyrus long-term potentiation (LTP) was affected 1 and 2 h after the fast injection, but not 4 h. In contrast, LTP was affected even 72 h after the slow injection. Aβ 1–42 staining 5 min after finish of the slow injection was more intense in the dentate granule cell layer than of the fast injection. The present study indicates that the retention of Aβ 1–42 in the extracellular fluid is correlated with neuronal Aβ 1–42 uptake and plays a key role in Aβ 1–42 neurotoxicity. In the extracellular fluid of the dentate gyrus, the retention period of Aβ 1–42 is much more critical for Aβ 1–42 toxicity than Aβ 1–42 concentration. It is likely that Aβ 1–42 toxicity is accelerated by the disturbance of Aβ 1–42 metabolism in the dentate gyrus.
关键词：amyloid β1–42;dentate gyrus long-term potentiation (LTP);Zn2+;freely moving rat
