In the last edition of PNAS, there is a very interesting paper in which the authors show that it's feasible to analyze the function of neuronal ionic channels in postmortem AD brains (1). The authors have extracted membrane complexes from postmortem temporal cortex of AD patients and controls, and injected it into Xenopus oocytes; the brains used in the report were frozen for 1-9 years, with a postmortem delay of 2-5 hours. Then, the authors recorded membrane currents elicited after an application of GABA. They found differences in the currents between patients and controls; no signal was seen in oocytes without injection. The study was under the direction of Dr. Ricardo Miledi (University of California, Irvine), and it was carried out as part of the postdoctoral work of Dr. Zulma Dueñas, a Pew Latin American Fellow.

The article, featured on the cover of PNAS, opens new avenues for AD research. The application of a new methodology for the functional analysis of neural molecular...  Read more

In the last edition of PNAS, there is a very interesting paper in which the authors show that it's feasible to analyze the function of neuronal ionic channels in postmortem AD brains (1). The authors have extracted membrane complexes from postmortem temporal cortex of AD patients and controls, and injected it into Xenopus oocytes; the brains used in the report were frozen for 1-9 years, with a postmortem delay of 2-5 hours. Then, the authors recorded membrane currents elicited after an application of GABA. They found differences in the currents between patients and controls; no signal was seen in oocytes without injection. The study was under the direction of Dr. Ricardo Miledi (University of California, Irvine), and it was carried out as part of the postdoctoral work of Dr. Zulma Dueñas, a Pew Latin American Fellow.

The article, featured on the cover of PNAS, opens new avenues for AD research. The application of a new methodology for the functional analysis of neural molecular complexes found in human brains, developed previously by the authors in cell lines (2), can have profound impact for future lines of research for etiologic factors of AD and for treatment strategies. For example, there are many studies searching for molecular structural differences in specific channel proteins between AD and control brains. In this context, the finding of differences in the quantity of acetylcholine or NMDA receptor subunits between patients and controls have led to the glutamatergic or cholinergic hypothesis, although to date there is no data about how these receptor systems are truly affected in AD brains. Although the published work has focused on the GABA system, it may be extended to the analysis of other channel systems.

The use of the described approach, in conjunction with other ones previously published (for example, cultures of brain tissues from postmortem material (4) and injection of mRNA from human brain in oocytes (5)), may be the beginning of the transition from a structural neuropathological perspective to a molecular neurophysiological approach of AD research (6).

References:
1. Miledi R, Dueñas Z, Martinez-Torres A, Kawas CH, Eusebi F. From The Cover: Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes. Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1760-3. Abstract

2. Palma E, Trettel F, Fucile S, Renzi M, Miledi R, Eusebi F. Microtransplantation of membranes from cultured cells to Xenopus oocytes: a method to study neurotransmitter receptors embedded in native lipids. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2896-900. Abstract

3. Terry AV Jr, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003 Sep;306(3):821-7. Abstract

4. Verwer RW, Baker RE, Boiten EF, Dubelaar EJ, van Ginkel CJ, Sluiter AA, Swaab DF. Post-mortem brain tissue cultures from elderly control subjects and patients with a neurodegenerative disease. Exp Gerontol. 2003 Jan-Feb;38(1-2):167-72. Abstract

5. Palma E, Esposito V, Mileo AM, Di Gennaro G, Quarato P, Giangaspero F, Scoppetta C, Onorati P, Trettel F, Miledi R, Eusebi F. Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15078-83. Abstract

6. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002 Oct 25;298(5594):789-91. Abstract

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