6月17日出版的《神经科学杂志》（Journal of Neuroscience）发表了中国科学院上海生命科学研究院神经科学研究所周嘉伟研究员和上海药物研究所镇学初研究员所领导科研团队的研究成果。他们发现，活化大脑星形胶质细胞的与磷脂酰肌醇耦联的多巴胺受体可以调节其产生碱性成纤维细胞生长因子（FGF-2） 的水平，从而发挥维持神经元存活、生长和促进脑修复的作用。这一成果是由博士研究生张新化等共同完成的。
FGF-2在大脑中主要来源于星形胶质细胞，它对神经发育和生长起着关键作用，因此，它的表达水平势必受到严格而精确的调节，但大脑是如何实现这一精确调节的尚不完全清楚。他们发现，活化与磷脂酰肌醇耦联的多巴胺受体能增强肌醇依赖的钙离子信号，提升FGF-2的产生，相反，活化经典的多巴胺受体则抑制胶质细胞内的钙信号，降低FGF-2的水平。另一方面，谷氨酸是经星形胶质细胞代谢的兴奋性神经递质，它也能诱发星形胶质细胞内的钙震荡，促进FGF-2的表达，表明在星形胶质细胞与神经元之间发生的谷氨酸-谷氨酰胺循环除了可以清除突触间隙谷氨酸以及为神经元合成谷氨酸提供原料外，还具有额外的功能，即通过参与调控细胞内钙信号来维持脑内生理水平的FGF-2。因此，本研究揭示了大脑内精确调控星形胶质细胞产生FGF-2的分子机理，这一发现同时还有助于今后建立对抗帕金森病大脑FGF-2水平下降的有效方法，从而提高神经保护的效果。（生物谷Bioon.com）
生物谷推荐原始出处：
The Journal of Neuroscience, June 17, 2009, 29(24):7766-7775; doi:10.1523/JNEUROSCI.0389-09.2009
Activation of Phosphatidylinositol-Linked D1-Like Receptor Modulates FGF-2 Expression in Astrocytes via IP3-Dependent Ca2+ Signaling
Xinhua Zhang,1,2,4 Zheng Zhou,2 Dakui Wang,2,3 Aiqun Li,1 Yanqing Yin,2 Xiaosong Gu,3 Fei Ding,3 Xuechu Zhen,5 and Jiawei Zhou2
1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, 2Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, 3Jiangsu Key Laboratory of Neuroregeneration and 4Department of Anatomy, Nantong University School of Medicine, Nantong, Jiangsu 226001, China, and 5State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China
Correspondence should be addressed to either of the following: Dr. Jiawei Zhou, Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; or Dr. Xuechu Zhen, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
Fibroblast growth factor-2 (FGF-2) is predominantly synthesized and secreted by astrocytes in adult brain. Our previous study showed that activation of classical dopamine receptor D1 or D2 elicits FGF-2 biosynthesis and secretion in astrocytes. Here, we report that astrocytic FGF-2 expression is also regulated by phosphatidylinositol (PI)-linked D1-like receptor. SKF83959, a selective PI-linked D1-like receptor agonist, upregulates the levels of FGF-2 protein in striatal astrocyte cultures in classical dopamine D1 and D2 receptor-independent manner. The conditional medium derived from SKF83959-activated astrocytes promoted the number of TH+ neurons in vitro. Treatment of astrocytes with SKF83959 increased intracellular calcium in two phases. Inhibition of intracellular calcium oscillation by inositol 1,4,5-triphosphate (IP3) inhibitors blocked the SKF83959-induced increase in FGF-2 expression. Moreover, intraperitoneal administration of SKF83959 reversed l-methyl-4-phenyl-l,2,3,6-tetrahydropypridine (MPTP)-induced reduction in FGF-2 expression in both the striatum and ventral midbrain and resulted in marked protection of dopaminergic neurons from MPTP-induced neurotoxicity. These results indicate that IP3/Ca2+/calmodulin-dependent protein kinase is an uncharted intracellular signaling pathway that is crucial for the regulation of FGF-2 synthesis in astrocytes. PI-linked D1-like receptor plays an important role in the regulation of astrocytic FGF-2 expression and neuroprotection which may provide a potential target for the drug discovery in Parkinson's disease.
