Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus

Abstract

New neurons continue to be born in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus of adult mammals, including humans. Previous work has shown that astrocytes function as the progenitors of these new neurons through immature intermediate D cells. In the first part of the present study, we determined the structure of each of these progenitors and how they are organized in three dimensions. Serial-section reconstructions of the SGZ, using confocal and electron microscopy demonstrate that SGZ astrocytes form baskets that hold clusters of D cells, largely insulating them from the hilus. Two types of glial fibrillary acidic protein-expressing astrocytes (radial and horizontal) and three classes of doublecortin and PSA-NCAM-positive D cells (D1, D2, D3) were observed. Radial astrocytes appear to interact closely with clusters of D cells forming radial proliferative units. In the second part of this study, we show that retrovirally labeled radial astrocytes give rise to granule neurons. We also used bromodeoxyuridine and [3H]thymidine labeling to study the sequence of appearance of the different D cells after a 7-day treatment with anti-mitotics. This analysis, together with retroviral labeling data, suggest that radial astrocytes divide to generate D1 cells, which in turn divide once to form postmitotic D2 cells. D2 cells mature through a D3 stage to form new granule neurons. These observations provide a model of how the germinal zone of the adult hippocampus is organized and suggest a sequence of cellular stages in the generation of new granule neurons.

The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

“…It has been described in studies using adult rodents that newborn neuronal cells show attenuated electrophysiological properties, such as field excitatory postsynaptic potentials (fEPSPs), which means that stimulation of a presynaptic terminal, e.g., the Schaffer collaterals, evokes a decreased postsynaptic response in the regenerated hippocampus. 7 These data indicate that the hippocampal environment no longer supports neuronal cell-fate commitment and functionality after HI. More systematic studies are necessary to clarify the mechanisms underlying impaired neuronal cell-fate commitment in the HI-injured brain.…”

“…44,45 Immature type II progenitors cells divide and will later show properties of neurons, e.g., express doublecortin (DCX), poly-sialylated neural adhesion molecule (PSA-NCAM), or neuronal nuclei (NeuN). 7,45,47 Until recently, NSCs had only been observed in the SVZ and SGZ of the healthy mammalian brain. However, an intriguing study identified neural progenitor cells in the neocortical layer 1 of adult rats subjected to mild ischemia.…”

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

“…Olfactory neuronal recruitment is rapid; in mice, it takes approximately 15 days for neuronally restricted progenitor cells of the SVZ to migrate through the rostral migratory stream to the olfactory bulb, traversing a distance of 3 to 5 mm, wherein they differentiate into olfactory interneurons [67,76,77] (for more detail see Whitman and Greer [78] and Abrous et al [79]). In addition, some neural stem cells migrate posteriorly in development to form a separate germinal neuroepithelium, the subgranular zone of the hippocampal dentate gyrus [80][81][82][83]. The population of neural stem cells that give rise to the neuronal progenitor pool of the anterior SVZ, which gives rise to the rostral migratory stream, is the pool of greatest interest in regard to HD therapeutics, because it is this pool from which new striatal neurons may be recruited (Fig.…”

HIV-1, chemokines and neurogenesis

“…New granule neurons differentiate and migrate the short distance between the SGZ and the inner portion of the granule cell layer. This process has been extensively studied, and many intermediate stages of progenitor cell development have been identified Seri et al, 2004). In contrast to this, the neural progenitors that form new interneurons in the OB are localized in the subventricular zone (SVZ) surrounding the lateral ventricle (Pencea and Luskin, 2003).…”

“…The close juxtaposition of the sites of expression of SDF-1 and its receptors suggest an interaction, whereby it would be possible for SDF-1 released from granule cells to influence progenitor cells (or neurons) in the immediate vicinity. Indeed, it has been suggested that granule neurons actually form mossy-like terminations (Kaplan and Bell, 1984) as well as other types of close contacts with progenitors in the SGZ (Seri et al, 2004). It is clear that there is a connection between these two types of cells so that changes of activity in the granule cell layer can regulate the rate of neurogenesis (Kronenberg et al, 2003), what has been described as "excitationneurogenesis" coupling (Deisseroth et al, 2004).…”