Co-expression of the P75 neurotrophin receptor and neurotrophin receptor-interacting melanoma antigen homolog in the mature rat brain

The p75 neurotrophin receptor (p75NTR) is involved in the regulation of neuronal survival and phenotype, but its signal transduction mechanisms are poorly understood. Recent evidence has implicated the cytoplasmic protein NRAGE (neurotrophin receptor-interacting MAGE (from Melanoma AntiGEn) homolog) in p75NTR signaling. To gain further insight into the role of NRAGE, we investigated the co-expression of NRAGE and p75NTR in mature rat brain. In all areas examined, NRAGE appeared to be confined to neurons. In the basal forebrain cholinergic complex, NRAGE immunoreactivity was evident in all p75NTR-positive neurons. There were many more NRAGE-positive than p75NTR-positive neurons in these regions, however. NRAGE was also expressed in areas of the basal forebrain that did not express p75NTR, including the lateral septal nucleus and the nucleus accumbens. A finding in marked contrast to previous studies was the presence of p75NTR immunoreactivity in neuronal cell bodies in the hippocampus. Hippocampal p75NTR immunoreactivity was apparent in rats 6 months and older, and was localized to the dentate gyrus and stratum oriens. All p75NTR-positive neurons in the dentate gyrus and hippocampal formation were positive for NRAGE. The majority of granular cells of the dentate gyrus and pyramidal cells in the hippocampal formation were positive for NRAGE and negative for p75NTR. NRAGE was also present in some neuronal populations that express p75NTR after injury, including striatal cholinergic interneurons, and motor neurons. A region of marked disparity was the cerebral cortex, in which NRAGE immunoreactivity was widespread whereas p75NTR was absent. The results are consistent with an important role for NRAGE in p75NTR signaling, as all cells that expressed p75NTR also expressed NRAGE. The wider distribution of NRAGE expression suggests that NRAGE may also participate in other signaling processes.