Diosgeninはアルツハイマー病モデルマウスの脳内において長距離の軸索再伸長を促進し記憶障害を改善する

抄録

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by Aβ deposition and neural networks disruption in the brain. We previously found that diosgenin, a constituent of Dioscorea Rhizoma, restored Aβ-induced axonal atrophy in neurons (in vitro) and recovered memory deficits in a mouse model of AD, 5XFAD. In the present study, we investigated whether diosgenin promoted long-distance axonal regeneration toward their intrinsic target area in 5XFAD brains, and clarified molecular mechanisms for accurate pathfinding of injured axons.

Retrograde tracing revealed that 14-day administration of diosgenin promoted axonal regeneration from the hippocampus to the prefrontal cortex, a neural circuit for memory formation, in 5XFAD mice. Subsequently, naïve neurons and axon-regenerated neurons in the brain slices were individually captured by laser microdissection to serve DNA microarray. Overexpression of the gene, whose expression was the most elevated in axon-regenerated neurons, to the hippocampal neurons promoted axonal regeneration in the brain and recovered memory deficits in 5XFAD mice.

Our study showed that axons in AD brains have capacities to regenerate toward long-distance original target by diosgenin administration. This finding proposes a novel therapeutic strategy to promote axonal regeneration for AD treatment.