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Stem- and progenitor cell proliferation in the dentate gyrus of the reeler mouse.

Sibbe M, Kuner E, Althof D, Frotscher M - PLoS ONE (2015)

Bottom Line: Here, we examined the local interrelation between Reelin expressing interneurons and putative hippocampal stem cells and investigated the effects of Reelin deficiency on stem cell and progenitor cell proliferation.Reelin-positive cells are found in close vicinity to putative stem cell processes, which would allow for stem cell regulation by Reelin.We investigated the proliferation of stem cells in the Reelin-deficient reeler hippocampus by Ki67 labeling and found a strong reduction of mitotic cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience, Institute of Anatomy and Cell Biology, University of Freiburg, Albertstr. 23, D-79104, Freiburg, Germany.

ABSTRACT
Adult hippocampal neurogenesis has been implicated in hippocampus-dependent learning and memory. Furthermore, the decline of neurogenesis accompanying aging could be involved in age-related cognitive deficits. It is believed that the neural stem cell niche comprises a specialized microenvironment regulating stem cell activation and maintenance. However, little is known about the significance of the extracellular matrix in controlling adult stem cells. Reelin is a large glycoprotein of the extracelluar matrix known to be of crucial importance for neuronal migration. Here, we examined the local interrelation between Reelin expressing interneurons and putative hippocampal stem cells and investigated the effects of Reelin deficiency on stem cell and progenitor cell proliferation. Reelin-positive cells are found in close vicinity to putative stem cell processes, which would allow for stem cell regulation by Reelin. We investigated the proliferation of stem cells in the Reelin-deficient reeler hippocampus by Ki67 labeling and found a strong reduction of mitotic cells. A detailed analysis of dividing Type 1, type 2 and type 3 cells indicated that once a stem cell is recruited for proliferation, the progression to the next progenitor stage as well as the number of mitotic cycles is not altered in reeler. Our data point to a role for Reelin in either regulating stem cell quiescence or maintenance.

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A Close proximity between a Reelin+ interneuron (red) and a GFAP+ putative stem cell (green) in the SGZ of a wild-type mice.B Example of close apposition of GFAP+ glial processes and a Reelin+ dendrite as revealed by electron microscopic double immunolabeling. Reelin labeling is visualized by DAB precipitate (yellow overlay), GFAP by gold particles (arrows). Scale bar in A: 10 μm, in B: 0.2 μm. GCL: granule cell layer, SGZ: subgranular zone.
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pone.0119643.g003: A Close proximity between a Reelin+ interneuron (red) and a GFAP+ putative stem cell (green) in the SGZ of a wild-type mice.B Example of close apposition of GFAP+ glial processes and a Reelin+ dendrite as revealed by electron microscopic double immunolabeling. Reelin labeling is visualized by DAB precipitate (yellow overlay), GFAP by gold particles (arrows). Scale bar in A: 10 μm, in B: 0.2 μm. GCL: granule cell layer, SGZ: subgranular zone.

Mentions: The major source of Reelin in the adult brain are Parvalbumin-expressing interneurons [28,29]. We further aimed to elucidate the morphological relationship of Reelin-expressing interneurons and GFAP+ stem cells of the SGZ. Using immunohistochemistry we could detect Reelin+ interneurons in close apposition to GFAP+ radial-oriented putative stem cells of the SGZ (Fig. 3A). Furthermore, in electron microscopic analysis GFAP+ and Reelin+ processes could be found in close apposition in the SGZ which is supporting a possible regulation of postnatal stem cells by Reelin secreted from interneurons (Fig. 3B). Measuring the extent of Reelin+ membrane covered by GFAP+ profiles resulted in 32.4 ± 3.2% coverage (from a total of nine examples).


Stem- and progenitor cell proliferation in the dentate gyrus of the reeler mouse.

Sibbe M, Kuner E, Althof D, Frotscher M - PLoS ONE (2015)

A Close proximity between a Reelin+ interneuron (red) and a GFAP+ putative stem cell (green) in the SGZ of a wild-type mice.B Example of close apposition of GFAP+ glial processes and a Reelin+ dendrite as revealed by electron microscopic double immunolabeling. Reelin labeling is visualized by DAB precipitate (yellow overlay), GFAP by gold particles (arrows). Scale bar in A: 10 μm, in B: 0.2 μm. GCL: granule cell layer, SGZ: subgranular zone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356578&req=5

pone.0119643.g003: A Close proximity between a Reelin+ interneuron (red) and a GFAP+ putative stem cell (green) in the SGZ of a wild-type mice.B Example of close apposition of GFAP+ glial processes and a Reelin+ dendrite as revealed by electron microscopic double immunolabeling. Reelin labeling is visualized by DAB precipitate (yellow overlay), GFAP by gold particles (arrows). Scale bar in A: 10 μm, in B: 0.2 μm. GCL: granule cell layer, SGZ: subgranular zone.
Mentions: The major source of Reelin in the adult brain are Parvalbumin-expressing interneurons [28,29]. We further aimed to elucidate the morphological relationship of Reelin-expressing interneurons and GFAP+ stem cells of the SGZ. Using immunohistochemistry we could detect Reelin+ interneurons in close apposition to GFAP+ radial-oriented putative stem cells of the SGZ (Fig. 3A). Furthermore, in electron microscopic analysis GFAP+ and Reelin+ processes could be found in close apposition in the SGZ which is supporting a possible regulation of postnatal stem cells by Reelin secreted from interneurons (Fig. 3B). Measuring the extent of Reelin+ membrane covered by GFAP+ profiles resulted in 32.4 ± 3.2% coverage (from a total of nine examples).

Bottom Line: Here, we examined the local interrelation between Reelin expressing interneurons and putative hippocampal stem cells and investigated the effects of Reelin deficiency on stem cell and progenitor cell proliferation.Reelin-positive cells are found in close vicinity to putative stem cell processes, which would allow for stem cell regulation by Reelin.We investigated the proliferation of stem cells in the Reelin-deficient reeler hippocampus by Ki67 labeling and found a strong reduction of mitotic cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience, Institute of Anatomy and Cell Biology, University of Freiburg, Albertstr. 23, D-79104, Freiburg, Germany.

ABSTRACT
Adult hippocampal neurogenesis has been implicated in hippocampus-dependent learning and memory. Furthermore, the decline of neurogenesis accompanying aging could be involved in age-related cognitive deficits. It is believed that the neural stem cell niche comprises a specialized microenvironment regulating stem cell activation and maintenance. However, little is known about the significance of the extracellular matrix in controlling adult stem cells. Reelin is a large glycoprotein of the extracelluar matrix known to be of crucial importance for neuronal migration. Here, we examined the local interrelation between Reelin expressing interneurons and putative hippocampal stem cells and investigated the effects of Reelin deficiency on stem cell and progenitor cell proliferation. Reelin-positive cells are found in close vicinity to putative stem cell processes, which would allow for stem cell regulation by Reelin. We investigated the proliferation of stem cells in the Reelin-deficient reeler hippocampus by Ki67 labeling and found a strong reduction of mitotic cells. A detailed analysis of dividing Type 1, type 2 and type 3 cells indicated that once a stem cell is recruited for proliferation, the progression to the next progenitor stage as well as the number of mitotic cycles is not altered in reeler. Our data point to a role for Reelin in either regulating stem cell quiescence or maintenance.

Show MeSH
Related in: MedlinePlus