Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure
Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure
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DOI：
10.1186/s12974-020-01762-z
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发表时间：
2020-03-20
影响因子：
9.3
通讯作者：
Korosi, Aniko
中科院分区：
文献类型：
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作者：
Abbink, Maralinde R.;Kotah, Janssen M.;Korosi, Aniko
背景：早期生活应激(ES)是阿尔茨海默病(AD)晚年发展的一个新的危险因素。我们之前已经在APPswe/PS1dE9小鼠模型中表明ES调节淀粉样β病理和小胶质细胞对它的反应。由于星形胶质细胞是AD发病机制中的关键角色，我们在这里研究了ES对野生型(WT)和APP/PS1小鼠星形胶质细胞的影响，以及这些影响与先前报道的淀粉样变性和小胶质细胞特征的关系。方法：我们通过限制出生后(P)2-9天的筑巢和铺垫材料来诱导ES。我们在WT小鼠(P9、P30和6月龄)和APP/PS1小鼠(4月和10月龄)上进行了研究：(I)海马(HPC)和内嗅皮层(EC)的GFAP覆盖率、细胞密度和复杂性；(Ii)星形胶质细胞标志物的海马区基因表达；(Iii)星形胶质细胞、小胶质细胞和淀粉样标志物之间的关系。结果：在WT鼠中，ES在P9和10月时增加了HPC亚区的GFAP覆盖率，并在10月时降低了它的覆盖率。10个月大的APP/PS1小鼠既有单个细胞的信号，也有成簇的GFAP信号。与WT小鼠相比，APP/PS1小鼠HPC中GFAP的总覆盖率降低，EC中GFAP总覆盖率增加，而HPC中聚集的GFAP信号覆盖率增加，并伴随着几个星形细胞基因表达的增加。虽然在APP/PS1小鼠中测得的星形细胞参数似乎没有受到ES的进一步调节，但在ES诱导的淀粉样变性和小胶质细胞变化的背景下分析这些参数，显示在4个月和10个月龄时的变化。结论：我们的数据表明ES导致星形细胞对淀粉样β病理的反应改变。
Background: Early-life stress (ES) is an emerging risk factor for later life development of Alzheimer's disease (AD). We have previously shown that ES modulates amyloid-beta pathology and the microglial response to it in the APPswe/PS1dE9 mouse model. Because astrocytes are key players in the pathogenesis of AD, we studied here if and how ES affects astrocytes in wildtype (WT) and APP/PS1 mice and how these relate to the previously reported amyloid pathology and microglial profile.Methods: We induced ES by limiting nesting and bedding material from postnatal days (P) 2-9. We studied in WT mice (at P9, P30, and 6 months) and in APP/PS1 mice (at 4 and 10 months) (i) GFAP coverage, cell density, and complexity in hippocampus (HPC) and entorhinal cortex (EC); (ii) hippocampal gene expression of astrocyte markers; and (iii) the relationship between astrocyte, microglia, and amyloid markers.Results: In WT mice, ES increased GFAP coverage in HPC subregions at P9 and decreased it at 10 months. APP/PS1 mice at 10 months exhibited both individual cell as well as clustered GFAP signals. APP/PS1 mice when compared to WT exhibited reduced total GFAP coverage in HPC, which is increased in the EC, while coverage of the clustered GFAP signal in the HPC was increased and accompanied by increased expression of several astrocytic genes. While measured astrocytic parameters in APP/PS1 mice appear not be further modulated by ES, analyzing these in the context of ES-induced alterations to amyloid pathology and microglial shows alterations at both 4 and 10 months of age.Conclusions: Our data suggest that ES leads to alterations to the astrocytic response to amyloid-beta pathology.