Elsevier

Neuroscience

Volume 133, Issue 2, 2005, Pages 381-392
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2005.01.067Get rights and content

Abstract

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.

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Animals and treatment

Rats of the Sprague-Dawley and Dark Agouti strains, of both sexes, were used. Sprague-Dawley rats were obtained from the Walter and Eliza Hall Animal Facility (Melbourne, Australia), and Dark Agouti rats from the Australian Research Council Animal Facility (Adelaide, Australia). Rats were housed in groups of two or three on a 12-h light/dark cycle with food and water available ad libitum. Animals aged 1, 3, 6, 12, 17, and 26 months were killed and perfused, and their brains were removed.

Basal forebrain

Specificity of the NRAGE antiserum was confirmed by Western blotting brain lysate from a mature rat (Fig. 1). Initial studies showed strong NRAGE immunoreactivity in the basal forebrain of 1-month and older rats, and this appeared to be neuronal (Fig. 2A). There were no NRAGE-positive stellate cell profiles, suggesting an absence of astrocytic expression. To test our impression that NRAGE was exclusively neuronal, sections through the basal forebrain of adult mouse brain were double-stained for

Discussion

Motivated by recent findings that implicate NRAGE as an important factor in p75NTR signaling, the present study was undertaken to look for evidence of co-expression of NRAGE and p75NTR in neurons of the mature rat brain. NRAGE was found to be expressed in virtually all neurons that expressed p75NTR. In the stratum oriens of the hippocampal formation, the frequency of NRAGE and p75NTR-positive neurons was roughly equivalent. In other areas, such as the dentate gyrus, medial septum, and the VDB

Acknowledgments

This work was supported by the National Health and Medical Research Council of Australia.

References (39)

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