ADAR2-dependent RNA editing of AMPA receptor subunit GluR2 determines vulnerability of neurons in forebrain ischemia

    Authors

    P. L. Peng; X. F. Zhong; W. H. Tu; M. M. Soundarapandian; P. Molner; D. Y. Zhu; L. Lau; S. H. Liu; F. Liu;Y. M. Lu

    Comments

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    Abbreviated Journal Title

    Neuron

    Keywords

    TRANSIENT CEREBRAL-ISCHEMIA; HIPPOCAMPAL CA1 NEURONS; CELL-DEATH; MESSENGER-RNA; KAINATE RECEPTORS; CA2+ PERMEABILITY; GLUTAMATE RELEASE; TEMPORAL PROFILE; PYRAMIDAL CELLS; RAT HIPPOCAMPUS; Neurosciences

    Abstract

    ADAR2 is a nuclear enzyme essential for GluR2 pre-mRNA editing at Q/R site-607, which gates Ca2+ entry through AMPA receptor channels. Here, we show that forebrain ischemia in adult rats selectively reduces expression of ADAR2 enzyme and, hence, disrupts RNA Q/R site editing of GluR2 subunit in vulnerable neurons. Recovery of GluR2 Q/R site editing by expression of exogenous ADAR2b gene or a constitutively active CREB, VP16-CREB, which induces expression of endogenous ADAR2, protects vulnerable neurons in the rat hippocampus from forebrain ischemic insult. Generation of a stable ADAR2 gene silencing by delivering small interfering RNA (siRNA) inhibits GluR2 Q/R site editing, leading to degeneration of ischemia-insensitive neurons. Direct introduction of the Q/R site edited GluR2 gene, GluR2(R-607), rescues ADAR2 degeneration. Thus, ADAR2-dependent GluR2 Q/R site editing determines vulnerability of neurons in the rat hippocampus to forebrain ischemia.

    Journal Title

    Neuron

    Volume

    49

    Issue/Number

    5

    Publication Date

    1-1-2006

    Document Type

    Article

    Language

    English

    First Page

    719

    Last Page

    733

    WOS Identifier

    WOS:000236070600013

    ISSN

    0896-6273

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