Rao Shilpa P, Sikdar Sujit Kumar
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Glia. 2007 Dec;55(16):1680-9. doi: 10.1002/glia.20564.
Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control.
如今，星形胶质细胞被认为是大脑中动态的信号传导元件。神经元与星形胶质细胞之间的双向通讯涉及星形胶质细胞对神经元输入的整合以及神经胶质递质的释放，这些递质可调节神经元兴奋性和突触传递。卵巢甾体激素17β-雌二醇除了对神经元电活动有快速作用外，还可通过膜相关雌激素受体迅速改变星形胶质细胞内钙浓度（[Ca2+]i）。我们使用钙成像和电生理技术，研究了雌二醇急性处理对混合海马培养物中星形胶质细胞-星形胶质细胞和星形胶质细胞-神经元通讯的功能影响。对一个星形胶质细胞进行机械刺激会引起受刺激星形胶质细胞内[Ca2+]i升高，并作为[Ca2+]i波传播到周围的星形胶质细胞。用雌二醇急性处理后，受刺激星形胶质细胞周围的星形胶质细胞中[Ca2+]i升高的幅度减弱。此外，雌二醇抑制了单个星形胶质细胞对代谢型谷氨酸受体激动剂反式-(+/-)-1-氨基-1,3-环戊二羧酸的[Ca2+]i升高。对星形胶质细胞进行机械刺激会诱导相邻神经元内[Ca2+]i升高和电生理反应。雌二醇迅速减弱了星形胶质细胞诱发的谷氨酸介导的神经元内[Ca2+]i升高和缓慢内向电流。此外，在存在雌二醇的情况下，星形胶质细胞诱导的自发突触后电流频率增加的发生率降低。雌二醇的作用具有立体特异性，洗脱后可逆。这些发现可能表明，星形胶质细胞对神经元兴奋性和突触传递的调节对雌二醇介导的快速激素控制敏感。
