Kuchibhotla Kishore V, Lattarulo Carli R, Hyman Bradley T, Bacskai Brian J
Massachusetts General Hospital, Department of Neurology/Alzheimer's Disease Research Laboratory, 114 16th Street, Charlestown, MA 02129, USA.
Science. 2009 Feb 27;323(5918):1211-5. doi: 10.1126/science.1169096.
Although senile plaques focally disrupt neuronal health, 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, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.
尽管老年斑会局部破坏神经元健康，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。我们利用多光子荧光寿命成像显微镜在体内对阿尔茨海默病小鼠模型中的星形胶质细胞钙稳态进行了定量成像。星形胶质细胞网络中的静息钙在整体上有所升高，但与单个斑块的距离无关。延时成像显示，星形胶质细胞中的钙瞬变更为频繁，在长距离上同步协调，并且与神经元活动解耦。此外，还观察到罕见的细胞间钙波，但仅在有β淀粉样蛋白斑块的小鼠中出现，起源于斑块附近并沿径向扩散至少200微米。因此，尽管在β淀粉样蛋白沉积物附近观察到神经毒性，但对局部病理存在更普遍的基于星形胶质细胞的网络反应。
