最近，科学家利用生物传感器揭示了一种常见的抗精神病药物治疗精神病的分子机制。这篇研究报告发表在12月13日的Nature Neuroscience杂志上。
精神病患者通常不仅会出现妄想和幻觉等症状，而且注意力很难维持。目前，治疗精神病最常用的药物是一种能够改善患者认知功能的药物——非典型抗精神病药(atypical neuroleptics)。非典型抗精神病药能引起神经递质乙酰胆碱的大量释放，但也有研究表明，这种药物会阻碍细胞表面受体接受神经递质传到的信息。
既然该药能够产生两种效应，那么研究人员对此提出疑问：究竟哪个方面占主导作用呢？
为了找到答案，课题组设计了一种特殊的生物学细胞CNiFERs(读作"sniffers")，当乙酰胆碱接触到这类细胞表面受体M1时，细胞就会改变颜色，这样就可以是科学家观察到M1受体何时接受到化学信号。
课题组将CNiFERs细胞植入到大鼠大脑内，然后刺激大脑的某个区域以促进乙酰胆碱的释放。研究人员观察到CNiFERs细胞颜色发生改变，这说明了CNiFERs能够发挥功能。然后，研究人员给大鼠分别使用了两种非典型抗精神病药。他们发现，这两种药物都能严重抑制CNiFERs对乙酰胆碱产生应答，这说明该药物阻断受体接受信息的作用比增加乙酰胆碱的量更显著。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Neuroscience 13 December 2009 | doi:10.1038/nn.2469
An in vivo biosensor for neurotransmitter release and in situ receptor activity
Quoc-Thang Nguyen1,7, Lee F Schroeder2,3,7, Marco Mank4, Arnaud Muller1, Palmer Taylor5, Oliver Griesbeck4 & David Kleinfeld1,3,6
Tools from molecular biology, combined with in vivo optical imaging techniques, provide new mechanisms for noninvasively observing brain processes. Current approaches primarily probe cell-based variables, such as cytosolic calcium or membrane potential, but not cell-to-cell signaling. We devised cell-based neurotransmitter fluorescent engineered reporters (CNiFERs) to address this challenge and monitor in situ neurotransmitter receptor activation. CNiFERs are cultured cells that are engineered to express a chosen metabotropic receptor, use the Gq protein–coupled receptor cascade to transform receptor activity into a rise in cytosolic [Ca2+] and report [Ca2+] with a genetically encoded fluorescent Ca2+ sensor. The initial realization of CNiFERs detected acetylcholine release via activation of M1 muscarinic receptors. We used chronic implantation of M1-CNiFERs in frontal cortex of the adult rat to elucidate the muscarinic action of the atypical neuroleptics clozapine and olanzapine. We found that these drugs potently inhibited in situ muscarinic receptor activity.
1 Physics Department, University of California San Diego, La Jolla, California, USA.
2 Medical Scientist Training Program, University of California San Diego, La Jolla, California, USA.
3 Graduate Program in Neurosciences, University of California San Diego, La Jolla, California, USA.
4 Max-Planck Institut für Neurobiologie, Martinsried, Germany.
5 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
6 Center for Neural Circuits and Behavior, University of California San Diego, La Jolla, California, USA.
7 These authors contributed equally to this work.
