最近,，科學(xué)家利用生物傳感器揭示了一種常見的抗精神病藥物治療精神病的分子機(jī)制。這篇研究報告發(fā)表在12月13日的Nature Neuroscience雜志上,。

精神病患者通常不僅會出現(xiàn)妄想和幻覺等癥狀,，而且注意力很難維持。目前,，治療精神病最常用的藥物是一種能夠改善患者認(rèn)知功能的藥物——非典型抗精神病藥(atypical neuroleptics),。非典型抗精神病藥能引起神經(jīng)遞質(zhì)乙酰膽堿的大量釋放，但也有研究表明,，這種藥物會阻礙細(xì)胞表面受體接受神經(jīng)遞質(zhì)傳到的信息,。

既然該藥能夠產(chǎn)生兩種效應(yīng)，那么研究人員對此提出疑問：究竟哪個方面占主導(dǎo)作用呢,？

為了找到答案,，課題組設(shè)計了一種特殊的生物學(xué)細(xì)胞CNiFERs(讀作"sniffers")，當(dāng)乙酰膽堿接觸到這類細(xì)胞表面受體M1時,，細(xì)胞就會改變顏色,，這樣就可以是科學(xué)家觀察到M1受體何時接受到化學(xué)信號。

課題組將CNiFERs細(xì)胞植入到大鼠大腦內(nèi),，然后刺激大腦的某個區(qū)域以促進(jìn)乙酰膽堿的釋放,。研究人員觀察到CNiFERs細(xì)胞顏色發(fā)生改變,，這說明了CNiFERs能夠發(fā)揮功能。然后,，研究人員給大鼠分別使用了兩種非典型抗精神病藥,。他們發(fā)現(xiàn)，這兩種藥物都能嚴(yán)重抑制CNiFERs對乙酰膽堿產(chǎn)生應(yīng)答,，這說明該藥物阻斷受體接受信息的作用比增加乙酰膽堿的量更顯著,。（生物谷Bioon.com）

生物谷推薦原始出處：

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.