Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease.,Glia

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Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease.
Glia ( IF 5.4 ) Pub Date : 2019-12-04 , DOI: 10.1002/glia.23759
Loukia Katsouri ₁ , Amy M Birch ₁ , Alexander W J Renziehausen ₁ , Carolin Zach ₁ , Yahyah Aman ₁ , Hannah Steeds ₁ , Angela Bonsu ₁ , Emily O C Palmer ₁ , Nazanin Mirzaei ₁ , Miriam Ries ₁ , Magdalena Sastre ₁

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The role of astrocytes in the progression of Alzheimer's disease (AD) remains poorly understood. We assessed the consequences of ablating astrocytic proliferation in 9 months old double transgenic APP23/GFAP-TK mice. Treatment of these mice with the antiviral agent ganciclovir conditionally ablates proliferating reactive astrocytes. The loss of proliferating astrocytes resulted in significantly increased levels of monomeric amyloid-β (Aβ) in brain homogenates, associated with reduced enzymatic degradation and clearance mechanisms. In addition, our data revealed exacerbated memory deficits in mice lacking proliferating astrocytes concomitant with decreased levels of synaptic markers and higher expression of pro-inflammatory cytokines. Our data suggest that loss of reactive astrocytes in AD aggravates amyloid pathology and memory loss, possibly via disruption of amyloid clearance and enhanced neuroinflammation.

中文翻译：

反应性星形胶质细胞的消融加剧了阿尔茨海默氏病模型中的疾病病理。

星形胶质细胞在阿尔茨海默氏病（AD）进程中的作用仍然知之甚少。我们评估了消除9个月大的双转基因APP23 / GFAP-TK小鼠星形细胞增殖的后果。用抗病毒药更昔洛韦治疗这些小鼠有条件地消除增殖的反应性星形胶质细胞。增殖性星形胶质细胞的丢失导致脑匀浆中单体淀粉样蛋白-β（Aβ）的水平显着增加，与酶促降解和清除机制降低相关。此外，我们的数据显示，缺乏增殖性星形胶质细胞的小鼠加剧了记忆缺陷，伴有突触标记物水平降低和促炎性细胞因子的较高表达。我们的数据表明，AD中反应性星形胶质细胞的丢失加重了淀粉样蛋白的病理学和记忆丧失，

更新日期：2019-12-04

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