Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice.
Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice.
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DOI：
10.1126/science.1169096
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发表时间：
2009-02-27
期刊：
影响因子：
--
通讯作者：
Bacskai BJ
中科院分区：
文献类型：
--
作者：
Kuchibhotla KV;Lattarulo CR;Hyman BT;Bacskai BJ
虽然老年斑对神经元的损伤是局灶性的，但星形胶质细胞对阿尔茨海默病病理的功能反应尚不清楚。利用体内多光子荧光寿命成像显微镜，我们对阿尔茨海默病小鼠模型的星形细胞钙稳态进行了定量成像。静息钙在星形细胞网络中整体升高，但与单个斑块的接近程度无关。时间推移成像显示，星形胶质细胞中的钙瞬变更频繁，远距离同步协调，与神经元活动脱钩。此外，还观察到罕见的细胞间钙波，但仅在有淀粉样蛋白β斑块的小鼠中观察到，起源于斑块附近，径向扩散至少200微米。因此，虽然神经毒性在淀粉样蛋白β沉积附近观察到，但存在更一般的星形胶质细胞网络对局灶性病理的反应。
While senile plaques injure neurons focally, the functional response of astrocytes to Alzheimer’s disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer’s disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time lapse imaging revealed that calcium transients in astrocytes were more frequent, were synchronously coordinated across long distances, and were uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-β plaques, originating near plaques and spreading radially at least 200 µm. Thus, while neurotoxicity is observed near amyloid-β deposits, there exists a more general astrocyte-based network response to focal pathology.
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影响因子：
64.8
作者：
Meyer-Luehmann, Melanie;Spires-Jones, Tara L.;Hyman, Bradley T.
通讯作者：
Hyman, Bradley T.
DOI：
10.1097/01.jnen.0000240468.12543.af
发表时间：
2006-11-01
影响因子：
3.2
作者：
Garcia-Alloza, Monica;Dodwell, Sarah A.;Bacskai, Brian J.
通讯作者：
Bacskai, Brian J.
影响因子：
16.2
作者：
Agulhon, Cendra;Petravicz, Jeremy;McMullen, Allison B.;Sweger, Elizabeth J.;Minton, Suzanne K.;Taves, Sarah R.;Casper, Kristen B.;Fiacco, Todd A.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
影响因子：
6.1
作者：
Garcia-Alloza, Monica;Robbins, Elissa M.;Frosch, Matthew P.
通讯作者：
Frosch, Matthew P.
影响因子：
4
作者：
Wilms, CD;Schmidt, H;Eilers, J
通讯作者：
Eilers, J