cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology
cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology
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DOI：
10.1093/cercor/bhv310
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发表时间：
2017-02-01
期刊：
影响因子：
3.7
通讯作者：
Ikegaya，Yuji
中科院分区：
文献类型：
--
作者：
Ujita，Sakiko;Sasaki，Takuya;Ikegaya，Yuji
在体外和体内，不同脑区的星形胶质细胞都表现出自发的细胞内钙升高；然而，这种活动的时间模式和功能都没有得到充分的评估。在这里，我们利用长期光学成像技术分析了4000多个星形胶质细胞在急性海马片以及头束缚小鼠的新皮质和海马区的钙活性。虽然星形胶质细胞的钙活动在很大程度上是稀疏和不规则的，但我们观察到一组细胞中的波动钙振荡以∼30 S的规则间隔重复。这些间歇性振荡i)依赖于2型三磷酸肌醇受体；ii)由单个星形胶质细胞胞体和突起之间的复杂反射相互作用组成；iii)与其他星形胶质细胞的胞体和突起不同步；iv)不需要神经元放电；v)通过cAMP-蛋白激酶A信号调节；vi)在病理条件下促进，如能量剥夺和癫痫样过度兴奋；和vii)与星形细胞突起肥大有关，星形胶质细胞肥大是反应性胶质增生症的早期特征，可在缺血和癫痫中观察到。因此，钙振荡似乎与星形胶质细胞的病理状态有关。
Astrocytes in various brain regions exhibit spontaneous intracellular calcium elevations both in vitro and in vivo; however, neither the temporal pattern underlying this activity nor its function has been fully evaluated. Here, we utilized a long-term optical imaging technique to analyze the calcium activity of more than 4000 astrocytes in acute hippocampal slices as well as in the neocortex and hippocampus of head-restrained mice. Although astrocytic calcium activity was largely sparse and irregular, we observed a subset of cells in which the fluctuating calcium oscillations repeated at a regular interval of ∼30 s. These intermittent oscillations i) depended on type 2 inositol 1,4,5-trisphosphate receptors; ii) consisted of a complex reverberatory interaction between the soma and processes of individual astrocytes; iii) did not synchronize with those of other astrocytes; iv) did not require neuronal firing; v) were modulated through cAMP-protein kinase A signaling; vi) were facilitated under pathological conditions, such as energy deprivation and epileptiform hyperexcitation; and vii) were associated with enhanced hypertrophy in astrocytic processes, an early hallmark of reactive gliosis, which is observed in ischemia and epilepsy. Therefore, calcium oscillations appear to be associated with a pathological state in astrocytes.