Hyperhomocysteinemia-Induced Gene Expression Changes in the Cell Types of the Brain.
Hyperhomocysteinemia-Induced Gene Expression Changes in the Cell Types of the Brain.
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DOI：
10.1177/1759091417742296
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发表时间：
2017-11
期刊：
影响因子：
4.7
通讯作者：
Wilcock DM
中科院分区：
文献类型：
--
作者：
Weekman EM;Woolums AE;Sudduth TL;Wilcock DM
血浆同型半胱氨酸水平高，称为高同型半胱氨酸血症，是血管认知障碍和痴呆症的危险因素，后者是痴呆症的第二大原因。虽然高同型半胱氨酸血症会导致小鼠微出血和认知能力下降，但高同型半胱氨酸血症对每种细胞类型的具体影响仍不清楚。我们分别培养星形胶质细胞、小胶质细胞、内皮细胞和神经细胞，分别给予中等水平的同型半胱氨酸处理24、48、72和96 小时。然后，我们确定了细胞特异性标志物和神经炎性标志物的基因表达变化，包括基质金属蛋白酶9系统。星形胶质细胞在72 时降低了几个星形细胞末端足部基因的水平，如水通道蛋白4和三磷酸腺苷敏感的内向整流钾通道，而在48 时增加了基质金属蛋白酶9的水平。小胶质细胞的基因变化显示，促炎标志物在48 小时达到峰值，抗炎标志物白介素1受体拮抗剂在72 小时达到峰值。内皮细胞在72 小时表达减少，而已知的改变tau磷酸化状态的激酶和磷酸酶在神经细胞中增加。这表明高同型半胱氨酸血症诱导了早期的小胶质细胞前炎症改变和星形细胞改变，这些改变与它们与血管系统的相互作用有关。总体而言，这些数据显示了高同型半胱氨酸血症如何影响阿尔茨海默病以及血管认知障碍和痴呆症。
High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr. We then determined the gene expression changes for cell-specific markers and neuroinflammatory markers including the matrix metalloproteinase 9 system. Astrocytes had decreased levels of several astrocytic end feet genes, such as aquaporin 4 and an adenosine triphosphate (ATP)-sensitive inward rectifier potassium channel at 72 hr, as well as an increase in matrix metalloproteinase 9 at 48 hr. Gene changes in microglia indicated a peak in proinflammatory markers at 48 hr followed by a peak in the anti-inflammatory marker, interleukin 1 receptor antagonist, at 72 hr. Endothelial cells had reduced occludin expression at 72 hr, while kinases and phosphatases known to alter tau phosphorylation states were increased in neuronal cells. This suggests that hyperhomocysteinemia induces early proinflammatory changes in microglia and astrocytic changes relevant to their interaction with the vasculature. Overall, the data show how hyperhomocysteinemia could impact Alzheimer’s disease and vascular cognitive impairment and dementia.
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影响因子：
11.2
作者：
Lee, JM;Yin, KJ;Xu, J
通讯作者：
Xu, J
DOI：
10.1186/alzrt262
发表时间：
2014
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Sudduth TL;Weekman EM;Brothers HM;Braun K;Wilcock DM
通讯作者：
Wilcock DM
影响因子：
20.1
作者：
GALIS, ZS;MUSZYNSKI, M;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
14.5
作者：
Reed, Bruce R.;Mungas, Dan M.;Chui, Helena C.
通讯作者：
Chui, Helena C.
影响因子：
3.5
作者：
Chen, ZT;Karaplis, AC;Rozen, R
通讯作者：
Rozen, R