暴露于β淀粉样蛋白的轴突终末可能不会导致突触前轴突损伤。
Axonal Terminals Exposed to Amyloid-β May Not Lead to Pre-Synaptic Axonal Damage.
作者信息
Sun Shu-Wei, Nishioka Christopher, Labib Wessam, Liang Hsiao-Fang
机构信息
Basic Sciences, Schools of Medicine, Loma Linda University, Loma Linda, CA, USA Radiation Medicine, Schools of Medicine, Loma Linda University, Loma Linda, CA, USA Pharmaceutical Science, School of Pharmacy, Loma Linda University, Loma Linda, CA, USA Neuroscience, University of California in Riverside, Riverside, CA, USA Bioengineering, University of California in Riverside, Riverside, CA, USA.
Neuroscience, University of California in Riverside, Riverside, CA, USA.
出版信息
J Alzheimers Dis. 2015;45(4):1139-48. doi: 10.3233/JAD-142154.
BACKGROUND
Synaptic deficits and neuronal loss are the major pathological manifestations of Alzheimer's disease. However, the link between the early synaptic loss and subsequent neurodegeneration is not entirely clear. Cell culture studies have shown that amyloid-β (Aβ) applied to axonal terminals can cause retrograde degeneration leading to the neuronal loss, but this process has not been demonstrated in live animals.
OBJECTIVE
To test if Aβ applied to retinal ganglion cell axonal terminals can induce axonal damage in the optic nerve and optic tract in mice.
METHODS
Aβ was injected into the terminal field of the optic tract, in the left lateral geniculate nucleus of wildtype C57BL/6 mice. Following the injection, monthly diffusion tensor imaging was performed. Three months after the injection, mice underwent visual evoked potential recordings, and then sacrificed for immunohistochemical examination.
RESULTS
There were no significant changes seen with diffusion tensor imaging in the optic nerve and optic tract 3 months after the Aβ injection. The myelin and axons in these regions remained intact according to immunohistochemistry. The only significant changes observed in this study were delayed transduction and reduced amplitude of visual evoked potentials, although both Aβ and its reversed form caused similar changes.
CONCLUSION
Despite the published in vitro studies, there was no significant axonal damage in the optic nerve and optic tract after injecting Aβ onto retinal ganglion cell axonal terminals of wildtype C57BL/6 mice.
背景
突触缺陷和神经元丢失是阿尔茨海默病的主要病理表现。然而，早期突触丢失与随后神经退行性变之间的联系尚不完全清楚。细胞培养研究表明，应用于轴突终末的β淀粉样蛋白（Aβ）可导致逆行性退变，进而导致神经元丢失，但这一过程尚未在活体动物中得到证实。
目的
测试应用于视网膜神经节细胞轴突终末的Aβ是否能诱导小鼠视神经和视束的轴突损伤。
方法
将Aβ注射到野生型C57BL/6小鼠左侧外侧膝状核的视束终末区域。注射后，每月进行扩散张量成像。注射后3个月，对小鼠进行视觉诱发电位记录，然后处死进行免疫组化检查。
结果
Aβ注射3个月后，视神经和视束的扩散张量成像未见明显变化。根据免疫组化结果，这些区域的髓鞘和轴突保持完整。本研究中观察到的唯一显著变化是视觉诱发电位的传导延迟和波幅降低，尽管Aβ及其反向形式均引起类似变化。
结论
尽管有已发表的体外研究，但将Aβ注射到野生型C57BL/6小鼠的视网膜神经节细胞轴突终末后，视神经和视束未出现明显的轴突损伤。
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