Adar2-Dependent Rna Editing Of Ampa Receptor Subunit Glur2 Determines Vulnerability Of Neurons In Forebrain Ischemia

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(R607), rescues ADAR2 degeneration. Thus, ADAR2-dependent GluR2 Q/R site editing determines vulnerability of neurons in the rat hippocampus to forebrain ischemia. ©2006 Elsevier Inc

Petri Lindebergii P. L. Civis Rostochiensis Chronicon Rostochiense Posthumum : Quinque libris absolutum. / [Hrsg. Nicolaus Petraeus. Beitr.: Markus Hasse, Johannes Possel d. Ä., Johannes Carstadius, Johannes Werner, Nikolaus, Rhodomann, Paul Neuwein, Paul Rutingius, Henricus Molnerus]

PETRI LINDEBERGII P. L. CIVIS ROSTOCHIENSIS CHRONICON ROSTOCHIENSE POSTHUMUM : QUINQUE LIBRIS ABSOLUTUM. / [HRSG. NICOLAUS PETRAEUS. BEITR.: MARKUS HASSE, JOHANNES POSSEL D. Ä., JOHANNES CARSTADIUS, JOHANNES WERNER, NIKOLAUS, RHODOMANN, PAUL NEUWEIN, PAUL RUTINGIUS, HENRICUS MOLNERUS] Petri Lindebergii P. L. Civis Rostochiensis Chronicon Rostochiense Posthumum : Quinque libris absolutum. / [Hrsg. Nicolaus Petraeus. Beitr.: Markus Hasse, Johannes Possel d. Ä., Johannes Carstadius, Johannes Werner, Nikolaus, Rhodomann, Paul Neuwein, Paul Rutingius, Henricus Molnerus] (1) Fotodokumentation (-) Titelseite (1) Lectori Benevolos (2) Widmung (3) Tituli (6) Chronicon Rost. Liber Primus (9) Chronicon Rost. Liber Secundus (41) Chronicon Rost. Liber Tertius (75