. 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. PubMed.


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  1. A Way to Study the Function of Ionic Channels in AD Brains

    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).

    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.

    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.

    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.

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