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Effects of optogenetic stimulation of basal forebrain parvalbumin neurons on Alzheimer's disease pathology.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-09-22 , DOI: 10.1038/s41598-020-72421-9
Caroline A Wilson 1 , Sarah Fouda 1 , Shuzo Sakata 1
Affiliation  

Neuronal activity can modify Alzheimer’s disease pathology. Overexcitation of neurons can facilitate disease progression whereas the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. Although previous studies have induced cortical gamma oscillations by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or sensory stimuli, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF by expressing channelrhodopsin-2 (ChR2) in PV+ neurons of 5xFAD mice. After 1-h induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. Amyloid plaques were accumulated more in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that beneficial effects of cortical gamma oscillations on Alzheimer’s disease pathology can depend on the induction mechanisms of cortical gamma oscillations.



中文翻译:


基底前脑小白蛋白神经元的光遗传学刺激对阿尔茨海默病病理学的影响。



神经元活动可以改变阿尔茨海默病的病理学。神经元的过度兴奋可以促进疾病进展,而皮质伽马振荡的诱导可以减少淀粉样蛋白负荷并改善小鼠模型的认知功能。尽管之前的研究通过光遗传学激活皮质小清蛋白阳性(PV+)神经元或感觉刺激来诱导皮质伽马振荡,但目前尚不清楚其他诱导伽马振荡的方法是否也有益。在这里,我们发现基底前脑 (BF) 中 PV+ 神经元的光遗传学激活会增加而不是减少淀粉样蛋白负担。我们通过在 5xFAD 小鼠的 PV+ 神经元中表达视紫红质通道蛋白 2 (ChR2),对 BF 施加 40 Hz 光刺激。在三天内诱导皮质伽玛振荡 1 小时后,我们观察到额叶皮质区域中淀粉样蛋白-β42 的浓度增加,但淀粉样蛋白-β40 的浓度没有增加。淀粉样斑块在内侧前额皮质和间隔核中积累较多,这两个区域都是 BF PV+ 神经元的目标。这些结果表明,皮质伽马振荡对阿尔茨海默病病理学的有益影响可能取决于皮质伽马振荡的诱导机制。

更新日期:2020-09-22
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