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. 2013 Sep 11:7:147.
doi: 10.3389/fncel.2013.00147. eCollection 2013.

The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging

Vivian Capilla-Gonzalez  1 , Arantxa Cebrian-Silla, Hugo Guerrero-Cazares, Jose M Garcia-Verdugo, Alfredo Quiñones-Hinojosa
Affiliations

The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging

Vivian Capilla-Gonzalez et al. Front Cell Neurosci. .

Abstract

The subventricular zone (SVZ) is the largest source of newly generated cells in the adult mammalian brain. SVZ-derived neuroblasts migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into mature neurons. Additionally, a small proportion of SVZ-derived cells contribute to the generation of myelinating oligodendrocytes. The production of new cells in the SVZ decreases during aging, affecting the incorporation of new neurons into the OB. However, the age-related changes that occur across the RMS are not fully understood. In this study we evaluate how aging affects the cellular organization of migrating neuroblast chains, the proliferation, and the fate of the newly generated cells in the SVZ-OB system. By using electron microscopy and immunostaining, we found that the RMS path becomes discontinuous and its cytoarchitecture is disorganized in aged mice (24-month-old mice). Subsequently, OB neurogenesis was impaired in the aged brain while the production of oligodendrocytes was not compromised. These findings provide new insight into oligodendrocyte preservation throughout life. Further exploration of this matter could help the development of new strategies to prevent neurological disorders associated with senescence.

Keywords: aging; neuroblast migration; neurogenesis; olfactory bulb; oligodendrogenesis; rostral migratory stream; subventricular zone.

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Figures

Figure 1
Figure 1
The population of neuroblasts within the RMS is disrupted during aging. Sagittal sections of the RMS in young and aged mice. (A) Young RMS stained with DAPI. (B) Aged RMS stained with DAPI, showing a notable reduction of cells in the migratory pathway (arrows). (C) Young RMS immunolabeled with GFAP. (D) Aged RMS immunolabeled with GFAP did not reveal remarkable differences in the population of GFAP+ cells. (E) Young RMS immunolabeled with DCX. (F) Aged RMS (arrows) immunolabeled with DCX, showing a notable reduction of neuroblasts. cc, corpus callosum; St, striatum; Lv, lateral ventricle. Scale bar: 100 μm
Figure 2
Figure 2
Cytoarchitecture of aged RMS reveals a loss of migrating neuroblasts into the gliotubes. Analysis of the RMS by using light and electron microscopy. (A) Bar graph depicting a significant reduction of the area occupied by the RMS in aged mice. (B) Semithin section of the young RMS showed multiples chains of neuroblasts. (C) Semithin section of the aged RMS showed a notable loss of migratory chains, but dispersed cells remained (arrows). Note the presence of groups of neuroblasts and astrocytes within the intrabulbar part of the anterior commissure (delineated). (D) Electron microscopy image of a young RMS showing a detail of the neuroblasts chains surrounded by astrocytic gliotubes. (E) Electron microscopy image showing a detail of the aged RMS, where neuroblasts were severely reduced. (F) Schematic representation of the RMS cytoarchitecture in young mice. Chains of neuroblasts (red) migrating through gliotubes, which were formed by astrocytes (blue). (G) Schematic representation of the RMS cytoarchitecture in aged mice. Note the loss of neuroblast migrating through the gliotubes. a, neuroblast; aci, intrabulbar part of the anterior commissure; b, astrocyte; Bv, blood vessel. Scale bar: B,C = 20 μm, D,E = 10 μm. *p < 0.01.
Figure 3
Figure 3
Aging decreases the population of proliferating cells in the RMS. (A) Bar graph depicting the number of BrdU+ cells in coronal sections of the RMS, 2 h after BrdU administration. Note the significant decrease of proliferative cells in the aged RMS. (B) Immunoassay against Ki67 (green) and GFAP (white) in sagittal sections of the RMS. The number of Ki67+ was drastically reduced in aged mice, while GFAP+ cells were maintained during aging. Note the presence of double Ki67/GFAP+ cells (arrow) in the young RMS. (C) Immunoassay against Ki67 (green) and DCX (red) in sagittal sections of the RMS. The number of both Ki67+ and DCX+ cells was drastically reduced in aged mice. Scale bar: B,C = 10 μm. *p < 0.01.
Figure 4
Figure 4
A high percentage of the RMS proliferative cells pertain to the oligodendroglial lineage. (A) Animals received a single dose of BrdU and were euthanized 2 h after. (B) Bar graph depicting the number of BrdU/Olig2+ cells in the RMS. Note that there is not a significant difference between young and aged mice. (C) Bar graph depicting the percentage of BrdU/Olig2+ cells in the RMS. (D) Immunostaining against BrdU (green), Olig2 (red), and GFAP (white) in coronal sections of the RMS. Note the presence of cells co-expressing BrdU and Olig2 markers. Sac, sacrifice. Scale bar: C = 20 μm. *p < 0.05.
Figure 5
Figure 5
Thymidine incorporation assay supports the generation of new oligodendrocytes in the aged RMS. (A) Animals received ten consecutive doses of 3H-Thy cells (dose/day) and were euthanized 6 weeks after. (B) Light and electron microscopy images showing a labeled cell (boxes) with irregular contours and light cytoplasm, with few intermediate filaments. The nucleus was fusiform and contained dense chromatin that was peripherally distributed. This cell contained features which bore a resemblance to astrocytes and oligodendrocytes. (C) Light and electron microscopy images showing a typical oligodendrocyte labeled with 3H-Thy (boxes). Sac, sacrifice. Scale bar: B = 5 μm, detail in (B) 2 μm, C = 10 μm, detail in (C) = 2 μm.
Figure 6
Figure 6
Aging decreases neurogenesis, but not oligodendrogenesis in the OB. (A) The animals received 4 doses of BrdU, separated by 2 h, and were euthanized 30 days after. (B) Bar graph depicting a significant reduction of BrdU+ cells in the aged OB, 30 days after treatment. (C) Bar graph depicting the number of NeuN and Olig2+ cells co-expressing BrdU marker. Note the decrease of newly generated neurons in aged mice, while the number of new oligodendrocytes remained unchanged. (D) Bar graph depicting the percentage of NeuN and Olig2+ cells co-expressing BrdU marker. (E) Immunostaining against NeuN (red) and BrdU (white) markers representing bar graphs in (B,C). (F) Immunostaining against Olig2 (red) and BrdU (green) markers representing bar graph in (B,C). (G) Immunostaining against BrdU (white), Olig2 (red), and NeuN (green) showing BrdU/Olig2/NeuN+ cells in the OB of aged mice. Sac, sacrifice. Scale bar: 40 μm. *p < 0.05, **p < 0.01.
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