Doublecortin expression in the adult rat telencephalon

Abstract

Doublecortin (DCX) is a protein required for normal neuronal migration in the developing cerebral cortex, where it is widely expressed in both radially and tangentially migrating neuroblasts. Moreover, it has been observed in the adult rostral migratory stream, which contains the neuronal precursors traveling to the olfactory bulb. We have performed DCX immunocytochemistry in the adult rat brain to identify precisely the neuronal populations expressing this protein. Our observations confirm the presence of DCX immunoreactive cells with the characteristic morphology of migrating neuroblasts in the subventricular zone, rostral migratory stream and the main and accessory olfactory bulbs. We have also found putative migratory cells expressing DCX in regions were no adult neuronal migration has been described, as the corpus callosum, the piriform cortex layer III/endopiriform nucleus and the striatum. Surprisingly, many cells with the phenotype of differentiated neurons were DCX immunoreactive; e.g. certain granule neurons in the hilar border of the granular layer of the dentate gyrus, some neuronal types in the piriform cortex layer II, granule and periglomerular neurons in the main and accessory olfactory bulbs, and isolated cells in the striatum. Almost all DCX immunoreactive cells also express the polysialylated form of neural cell adhesion molecule and have a similar distribution to rat collapsin receptor-mediated protein-4, two molecules involved in neuronal structural plasticity. Given these results, we hypothesize that DCX expression in differentiated neurons could be related to its capacity for microtubule reorganization and that this fact could be linked to axonal outgrowth or synaptogenesis.

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“…Furthermore, the oval, triangular, or spindle-shaped nuclei of these cells were significantly smaller than of any cortical neurons in the same tissue. Because NeuN may not be a definitive neuronal marker (Wolf et al, 1997;Teo et al, 1999), we also performed anti-DCX staining, which labels perinuclear cytoplasm of migrating young neurons (Gleeson et al, 1999;Nacher et al, 2001). With this method, we observed two BrdUϩ cells that were weakly costained with this marker in Ͼ100 slices examined (Fig.…”

“…We also avoided high doses of BrdU to avoid its possible mutagenic and stimulation effect on DNA synthesis (Nowakowski and Hayes, 2001;Rakic, 2002b). To identify the phenotypes of BrdU-labeled cells in the neocortex, an immunohistochemical analysis was performed with neuronal markers NeuN, a transcriptional factor that is expressed in the nucleus and cytoplasm of neurons (Mullen et al, 1992), and doublecortin (DCX) (Gleeson et al, 1999;Nacher et al, 2001) and also with markers of other non-neuronal cell types. GFAP and S-100␤ (astroglial cell), O4 (oligodendrocyte), and Iba-1 (microglial cell) (Ito et al, 1998) were used.…”

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

“…This cytoskeletal protein is present in cytoplasm, neurites, and growth cones of neuroblasts and young neurons in the adult neurogenic regions. 11,48 In P95E rats, the DCX-immunopositive ( þ ) cells were aligned along the dorsal and ventral blades of the SGZ (Figure 2b). In general, DCX þ cells had well developed apical dendrites, in many cases running from the soma to the lateral ventricle.…”

“…10 The neuroblasts then migrate a short distance to the granular layer and differentiate to mature granular neurons. Newly generated neuroblasts and immature neurons in the adult DG specifically express doublecortin (DCX), 11 a microtubule-associated phosphoprotein also expressed in migrating neuroblasts and immature neurons during development. Most importantly, newly born granular neurons are incorporated into the neural circuitry and mature into functional neurons.…”

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“…Scale bar: 100 m for G and I; 50 m for A, B, E, F, H, and J; 25 m for C and D. occur in newly formed, PSA-NCAM (neural cell adhesion molecule) positive granule neurons during maturation (Nakagawa et al, 2002;Zhu, Lau, Liu, Wei, & Lu, 2004). Because there is an almost complete overlap between DCX expression and NCAM polysialylation (Nacher, Crespo, & McEwen, 2001), we supposed that the pCREB-positive cells in the granule cell layer, located at the border with the hilus, were in fact newly formed neurons. This assumption was confirmed by the significant correlation that we found between the number of DCX-expressing neurons and the number of pCREB-positive cells, R 2 ϭ .62, p Յ .001.…”