Expression of Nuclear Orphan Receptors Ngfi-B/Tr3, Nurr1 And Nor-1 after Global Brain Ischemia in Rat.

Abstract

INTRODUCTION. Neuron-derived orphan receptor (NOR-1) was cloned from cultured embryonal neurons undergoing apoptotic cell death. NOR-1 is related to the nuclear orphan receptors, NGFI-B and NURR1, which interact with the retinoic acid receptor, RXR. NGFI-B and NURR1 are immediate early genes in the ischemic brain, suggesting a role in repair or cell death. Very recently, NGFI-B/TR3 was found to exert a pro-apoptotic effect through mitochondrial targeting and cytochrome release leading to apoptosis (1). Such dual role of NGFI-B (and related orphans) in nuclear and mitochondrial function could be important for neuronal damage in brain ischemia (stroke). We evaluated novel gene expression (mRNA levels) of nuclear orphan receptors after short brain ischemia. This model allows to correlate changes in gene and protein expression with pathological outcome, i.e. selective vulnerability occurs in CA1 neurons of the hippocampus while the adjacent CA3 cells and the dentate granule cells survive.