Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain.

Throughout life, the anterior part of the postnatal rodent subventricular zone (SVZa), surrounding the lateral ventricles, contains a prolific source of neuronal progenitor cells that retain their capacity to concurrently generate neurons and migrate along the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into interneurons. This study was designed to determine whether the SVZ and RMS of the postnatal primate also harbor a specialized population of neuronal progenitors with the capacity to divide while they migrate. In order to reveal the spatial-temporal changes in the distribution and composition of the neuronal progenitor cells in the primate SVZ and RMS, seven rhesus monkeys, ranging in age from 2 days to 8 years, were given a single injection of the cell proliferation marker bromodeoxyuridine (BrdU) 3 h before they were perfused. The phenotypic identity of the BrdU(+) cells was revealed by double labeling sagittal sections with cell type-specific markers. From birth onward the distribution of BrdU(+) cells with a neuronal phenotype is extensive and largely overlapping with that of the rodent. Similar to the rodent brain the neuronal progenitors are most numerous in neonates. The BrdU(+) neurons in the primate forebrain extend lateral and ventral to the lateral ventricle and all along the RMS. The cytoarchitectonic arrangement and appearance of the neuronal progenitor cells is quite varied in the primate compared to the rodent; in some locations the cells are aligned in parallel arrays resembling the neuronal chains of the adult rodent RMS, whereas in other positions the cells have a homogeneous "honeycomb" arrangement. The chains are progressively more pervasive in older primates. Akin to the RMS of adult rodents, in the primate SVZ and RMS the astrocytes often form long tubes enveloping the chains of neuronal progenitors. Our study demonstrates that the primate forebrain, similar to the rodent forebrain, harbors a specialized population of mitotically active neuronal progenitor cells that undergo extensive rearrangements while continuing to proliferate throughout life.

Pencea V ，Bingaman KD ，Freedman LJ ，Luskin MB ... -  《EXPERIMENTAL NEUROLOGY》

Subventricular zone-derived neuronal progenitors migrate into the subcortical forebrain of postnatal mice.

De Marchis S ，Fasolo A ，Puche AC 《JOURNAL OF COMPARATIVE NEUROLOGY》

Prenatal development of the rodent rostral migratory stream.

The aim of this study was to elucidate the embryological origins of the unique neuronal progenitor cells that form the rostral migratory stream (RMS), the path traversed by cells from the anterior part of the forebrain subventricular zone (SVZa) en route to the olfactory bulb. To determine when and where cells constituting the RMS initially exhibit their characteristic neuronal phenotype and high mitotic capacity, we analyzed the cells of the rat forebrain between embryonic day 14 (E14) and postnatal day 2 (P2). At E14, cells with a neuronal phenotype were observed within the ventricular zone in close proximity to the mantle layer of the future olfactory bulb. By E15, cells expressing neuronal markers are also PSA-NCAM immunoreactive and become aligned in chains of similarly oriented cells, a hallmark of the postnatal RMS. The cells that form chains organize into a patch that enlarges in the anterior-posterior and medial-lateral dimensions from E16 to E22 (birth). In comparing the forebrain cytoarchitecture to the pattern of cell type-specific staining, the patch constitutes only the central part of the proximal RMS. Early during development, the region of the RMS surrounding the patch expresses low levels of PSA-NCAM and neuron-specific markers. The proliferative activity of cells forming the patch vs. nonpatch regions of the RMS was analyzed following a short bromodeoxyuridine (BrdU) exposure. Between E15 and E22, the patch can be recognized by the mitotic activity of its cells; the cells of the patch incorporate less BrdU than the nonpatch portion of the RMS. The time course of appearance of cells forming the RMS indicates that the RMS arises in advance and independently of the cortical SVZ. Although the patch and the nonpatch regions of the embryonic RMS appear to merge postnatally, the two regions may originate separately under the influence of distinct intrinsic and extrinsic factors.

Pencea V ，Luskin MB 《JOURNAL OF COMPARATIVE NEUROLOGY》

Neurogenesis and neuronal migration in the neonatal rat forebrain anterior subventricular zone do not require GFAP-positive astrocytes.

Law AK ，Pencea V ，Buck CR ，Luskin MB ... -  《DEVELOPMENTAL BIOLOGY》

Enhanced proliferation of progenitor cells in the subventricular zone and limited neuronal production in the striatum and neocortex of adult macaque monkeys after global cerebral ischemia.

Cerebral ischemia in adult rodent models increases the proliferation of endogenous neural progenitor cells residing in the subventricular zone along the anterior horn of the lateral ventricle (SVZ a) and induces neurogenesis in the postischemic striatum and cortex. Whether the adult primate brain preserves a similar ability in response to an ischemic insult is uncertain. We used the DNA synthesis indicator bromodeoxyuridine (BrdU) to label newly generated cells in adult macaque monkeys and show here that the proliferation of cells with a progenitor phenotype (double positive for BrdU and the markers Musashi 1, Nestin, and beta III-tubulin) in SVZ a increased during the second week after a 20-min transient global brain ischemia. Subsequent progenitor migration seemed restricted to the rostral migratory stream toward the olfactory bulb and ischemia increased the proportion of adult-generated cells retaining their location in SVZ a with a progenitor phenotype. Despite the lack of evidence for progenitor cell migration toward the postischemic striatum or prefrontal neocortex, a small but sustained proportion of BrdU-labeled cells expressed features of postmitotic neurons (positive for the protein Neu N and the transcription factors Tbr 1 and Islet 1) in these two regions for at least 79 days after ischemia. Taken together, our data suggest an enhanced neurogenic response in the adult primate telencephalon after a cerebral ischemic insult.

Tonchev AB ，Yamashima T ，Sawamoto K ，Okano H ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》