Neuroscience Back from the Dead

John F. Foley

Science Signaling, AAAS, Washington, DC 20005, USA

Autism comprises a complex spectrum of neurodevelopmental disorders, likely caused by a number of different factors, most of which are unknown. The receptors for -aminobutyric acid (GABA) and glutamate are implicated in the development of autism, but the study of these and other neurotransmitter receptors in brain tissue is technically challenging. Limon et al. used two techniques to investigate proteins derived from postmortem brain tissue from age-matched normal and autistic subjects. First, the authors isolated poly(A⁺) RNA from small quantities of brain tissue and microinjected these samples into Xenopus oocytes. Samples were taken from the cerebellum and the temporal cortex because these areas show abnormal neuronal organization in autistic patients. Even though the brains had been in storage for 2 to 5 years, they still contained intact mRNAs that gave rise to a number of different neurotransmitter receptors and voltage-operated ion channels in the injected oocytes, as assessed by electrophysiology experiments. In a second strategy, called microtransplantation, the authors made membrane preparations from the brain tissues, microinjected them into oocytes, and allowed the brain-derived membranes to fuse with the oocyte plasma membrane in a process similar to exocytosis. Electrophysiology experiments showed that the native receptors from the postmortem tissue were functional. Although some trends were observed, no significant molecular differences were found between autistic subjects and the controls. However, as Spitzer discusses, the real strengths of this study are the demonstration that native membrane proteins can still be assayed after long postmortem intervals and the adaptability of this experimental system to the study of other disease states.

A. Limon, J. M. Reyes-Ruiz, R. Miledi, Microtransplantation of neurotransmitter receptors from postmortem autistic brains to Xenopus oocytes. Proc. Natl. Acad. Sci. U.S.A. 105, 10973-10977 (2008). [Abstract] [Full Text]

N. C. Spitzer, A Rosetta stone for analysis of human membrane protein function. Proc. Natl. Acad. Sci. USA. 105, 10641-10642 (2008). [Full Text]