6月17日出版的《神經(jīng)科學(xué)雜志》（Journal of Neuroscience）發(fā)表了中國科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所周嘉偉研究員和上海藥物研究所鎮(zhèn)學(xué)初研究員所領(lǐng)導(dǎo)科研團隊的研究成果,。他們發(fā)現(xiàn),，活化大腦星形膠質(zhì)細胞的與磷脂酰肌醇耦聯(lián)的多巴胺受體可以調(diào)節(jié)其產(chǎn)生堿性成纖維細胞生長因子（FGF-2） 的水平,，從而發(fā)揮維持神經(jīng)元存活,、生長和促進腦修復(fù)的作用。這一成果是由博士研究生張新化等共同完成的,。
FGF-2在大腦中主要來源于星形膠質(zhì)細胞,，它對神經(jīng)發(fā)育和生長起著關(guān)鍵作用，因此,，它的表達水平勢必受到嚴格而精確的調(diào)節(jié),，但大腦是如何實現(xiàn)這一精確調(diào)節(jié)的尚不完全清楚。他們發(fā)現(xiàn),，活化與磷脂酰肌醇耦聯(lián)的多巴胺受體能增強肌醇依賴的鈣離子信號，提升FGF-2的產(chǎn)生,，相反,，活化經(jīng)典的多巴胺受體則抑制膠質(zhì)細胞內(nèi)的鈣信號，降低FGF-2的水平,。另一方面,，谷氨酸是經(jīng)星形膠質(zhì)細胞代謝的興奮性神經(jīng)遞質(zhì)，它也能誘發(fā)星形膠質(zhì)細胞內(nèi)的鈣震蕩,，促進FGF-2的表達,，表明在星形膠質(zhì)細胞與神經(jīng)元之間發(fā)生的谷氨酸-谷氨酰胺循環(huán)除了可以清除突觸間隙谷氨酸以及為神經(jīng)元合成谷氨酸提供原料外，還具有額外的功能,，即通過參與調(diào)控細胞內(nèi)鈣信號來維持腦內(nèi)生理水平的FGF-2,。因此，本研究揭示了大腦內(nèi)精確調(diào)控星形膠質(zhì)細胞產(chǎn)生FGF-2的分子機理,，這一發(fā)現(xiàn)同時還有助于今后建立對抗帕金森病大腦FGF-2水平下降的有效方法,，從而提高神經(jīng)保護的效果。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
