F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Neurobiol Dis. 2010 Nov;40(2):386-93. doi: 10.1016/j.nbd.2010.06.014. Epub 2010 Jul 6.
Long-term potentiation (LTP) and neurogenesis in the dentate gyrus (DG) are correlated forms of hippocampal plasticity which share, under physiological conditions, common regulatory mechanisms. In Alzheimer's disease (AD), their alterations are potentially associated with the early cellular pathology and cognitive decline. We analyzed DG LTP and neurogenesis in B6.152H mice, an amyloid precursor protein and presenilin 2 double-transgenic mouse model of amyloidosis and observed that DG LTP was strongly enhanced before and after amyloid plaque formation. Whereas proliferation of DG neuronal progenitor cells was unchanged, survival of newborn neurons was strongly decreased already before plaque formation. As similar alteration of neurogenesis was observed in PS2APP mice without changes in DG LTP (Richards et al. 2003), this study suggests that enhanced synaptic plasticity did not rescue impaired neurogenesis, and supports decreased survival of newborn neurons as an early event associated with AD detectable even before plaque formation.
长时程增强（LTP）和齿状回（DG）中的神经发生是海马可塑性的相关形式，在生理条件下，它们具有共同的调节机制。在阿尔茨海默病（AD）中，它们的改变可能与早期的细胞病理学和认知能力下降有关。我们分析了 B6.152H 小鼠的 DG LTP 和神经发生，B6.152H 是淀粉样前体蛋白和早老素 2 的双转基因淀粉样变性小鼠模型，结果发现 DG LTP 在淀粉样斑块形成前后明显增强。虽然 DG 神经元祖细胞的增殖没有变化，但在斑块形成之前，新生神经元的存活率就已经明显下降。由于在没有 DG LTP 改变的 PS2APP 小鼠中也观察到类似的神经发生改变（Richards 等人，2003），因此本研究表明，增强的突触可塑性并不能挽救受损的神经发生，并且支持新生神经元的存活减少是与 AD 相关的早期事件，甚至在斑块形成之前就可以检测到。
