Limon Agenor, Reyes-Ruiz Jorge Mauricio, Miledi Ricardo
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA.
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10973-7. doi: 10.1073/pnas.0804386105. Epub 2008 Jul 21.
Autism is a complex disorder that arises from the pervasive action of genetic and epigenetic factors that alter synaptic connectivity of the brain. Although GABA and glutamate receptors seem to be two of those factors, very little is known about the functional properties of the autistic receptors. Autistic tissue samples stored in brain banks usually have relatively long postmortem times, and it is highly desirable to know whether neurotransmitter receptors in such tissues are still functional. Here we demonstrate that native receptors microtransplanted from autistic brains, as well as de novo mRNA-expressed receptors, are still functional and susceptible to detailed electrophysiological characterization even after long postmortem intervals. The opportunity to study the properties of human receptors present in diseased brains not only opens new avenues toward understanding autism and other neurological disorders, but it also makes the microtransplantation method a useful translational system to evaluate and develop novel medicinal drugs.
自闭症是一种复杂的疾病，由改变大脑突触连接性的遗传和表观遗传因素的普遍作用引起。虽然GABA和谷氨酸受体似乎是其中两个因素，但对于自闭症受体的功能特性知之甚少。存储在脑库中的自闭症组织样本通常有较长的死后时间，非常有必要了解此类组织中的神经递质受体是否仍具有功能。在此我们证明，即使经过长时间的死后间隔，从自闭症大脑中微移植的天然受体以及从头mRNA表达的受体仍然具有功能，并且易于进行详细的电生理表征。研究患病大脑中存在的人类受体特性的机会不仅为理解自闭症和其他神经疾病开辟了新途径，还使微移植方法成为评估和开发新型药物的有用转化系统。
