Transient expression of doublecortin during adult neurogenesis

Abstract

During development of the central nervous system, expression of the microtubule binding protein doublecortin (DCX) is associated with migration of neuroblasts. In addition to this developmental role, expression of DCX remains high within certain areas of the adult mammalian brain. These areas, mainly the dentate gyrus and the lateral ventricle wall in conjunction with the rostral migratory stream and olfactory bulb, retain the capacity to generate new neurons into adulthood. Adult neurogenesis is typically detected by incorporation of bromodeoxyuridine (BrdU) into dividing cells and colabeling of BrdU-positive cells with markers for mature neurons. To elucidate whether DCX could act as an alternative indicator for adult neurogenesis, we investigated the temporal expression pattern of DCX in neurogenic regions of the adult brain. Analysis of newly generated cells showed that DCX is transiently expressed in proliferating progenitor cells and newly generated neuroblasts. As the newly generated cells began expressing mature neuronal markers, DCX immunoreactivity decreased sharply below the level of detection and remained undetectable thereafter. The transient expression pattern of DCX in neuronal committed progenitor cells/neuroblasts indicates that DCX could be developed into a suitable marker for adult neurogenesis and may provide an alternative to BrdU labeling. This assumption is further supported by our observation that the number of DCX-expressing cells in the dentate gyrus was decreased with age according to the reduction of neurogenesis in the aging dentate gyrus previously reported.

Cell Proliferation is Influenced by Bulbectomy and Normalized by Imipramine Treatment in a Region-Specific Manner

“…We found that the basal levels of cells incorporating BrdU in the hippocampus and SVZ of sham-operated control animals were consistent with those of previous reports (Kempermann and Gage, 2000;Mandairon et al, 2003;Brown et al, 2003;Yang et al, 2004). In the SVZ, BrdUpositive cells were concentrated in a tight band in the dorsal area (Figure 1a), and in a looser network of single cells in the ventral area.…”

Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

“…This is true for the dSVZ and extends up to the lesion core, where strong DCX upregulation can be seen. The expression of DCX, a marker for migrating neuronal progenitors, is an indication of neurogenesis as in the adult brain, within areas of continuous neurogenesis (Brown et al, 2003), or in case of increase in brain neurogenesis induced by environmental factors or insults (Couillard-Despres et al, 2005). Such an increase in neurogenesis following QA injection is in line with previous findings (Tattersfield et al, 2004;Collin et al, 2005).…”

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

“…WBI decreased the density of DCX + , neurons in young adults, as previously reported (8,11,13), but had no effect on the density of DCX + cells in old rats ( Figure 2). One must be circumspect when interpreting the effects of a change or lack of change in the number of DCX + cells on neuronal replacement (34,(45)(46)(47); DCX is expressed in dividing neuroblasts and for approximately two weeks in differentiating, post-mitotic immature neurons (34,45) but not all DCX + neurons survive to maturity. Where examined in previous studies, however, WBI-induced decreases in neurogenesis in younger animals demonstrated by S-phase labeling with bromodeoxyuridine (BrdU) combined with neuron specific markers have been paralleled by decreases in DCX labeling (8,11).…”