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Null effect of antidepressants on the astrocytes-mediated proliferation of hippocampal progenitor cells in vitro.

Ko HG, Lee SJ, Son H, Kaang BK - Mol Pain (2007)

Bottom Line: The increase of neurogenesis might contribute to the behavioral effects of antidepressants.In both of these systems, in comparison with naïve astrocytes, antidepressant-treated astrocytes did not further increase the proliferation of NPCs.These results suggest that astrocytes increase the proliferation of hippocampal NPCs, however, this may not be directly involved in the antidepressant-induced proliferation of NPCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Creative Research Initiative Center for Memory and Institute of Molecular Biology and Genetics, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Gwanak-gu, Seoul, Korea. dhelix2@snu.ac.kr

ABSTRACT

Background: It is well known that antidepressants increase neurogenesis in the dentate gyrus of the hippocampus. The increase of neurogenesis might contribute to the behavioral effects of antidepressants. However, the mechanism by which antidepressants increase hippocampal neurogenesis is largely unknown. It has been recently reported that astroglia induce the neurogenesis of the hippocampal neural progenitor cells (NPCs). Therefore, we hypothesized that antidepressants may act on astrocytes, and this in turn induces neurogenesis of NPCs.

Results: To examine this hypothesis, we used two co-culture systems, i.e., a contact-independent Banker culture and a contact-dependent overlay co-culture. In both of these systems, in comparison with naïve astrocytes, antidepressant-treated astrocytes did not further increase the proliferation of NPCs.

Conclusion: These results suggest that astrocytes increase the proliferation of hippocampal NPCs, however, this may not be directly involved in the antidepressant-induced proliferation of NPCs.

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Related in: MedlinePlus

Effects of antidepressant-activated astrocytes on the proliferation of NPCs in a contact-independent culture system. (A) Proliferation of NPCs co-cultured with astrocytes using the Banker culture system. The astrocytes were not in contact with NPCs and could affect NPCs only through a diffusible factor. After BrdU immunocytochemical analysis, the nuclei were stained with DAPI (blue). An arrowhead (pink color) marks BrdU-labeled NPCs. Scale bar, 50 μm. (B) Quantification of the proliferation of NPCs. NPCs in control group were not exposed to astrocytes. In comparison with the control group, naïve astrocytes increased the number of BrdU (+) NPCs. However, in comparison with naïve astrocytes, those treated with 10 μM of desipramine or fluoxetine did not further increase the proliferation of NPCs (p > 0.05). Data shown are mean values ± SEM. One-way ANOVA was used for intergroup comparison, Tukey's multiple comparison test was used for post-hoc comparisons.
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Figure 2: Effects of antidepressant-activated astrocytes on the proliferation of NPCs in a contact-independent culture system. (A) Proliferation of NPCs co-cultured with astrocytes using the Banker culture system. The astrocytes were not in contact with NPCs and could affect NPCs only through a diffusible factor. After BrdU immunocytochemical analysis, the nuclei were stained with DAPI (blue). An arrowhead (pink color) marks BrdU-labeled NPCs. Scale bar, 50 μm. (B) Quantification of the proliferation of NPCs. NPCs in control group were not exposed to astrocytes. In comparison with the control group, naïve astrocytes increased the number of BrdU (+) NPCs. However, in comparison with naïve astrocytes, those treated with 10 μM of desipramine or fluoxetine did not further increase the proliferation of NPCs (p > 0.05). Data shown are mean values ± SEM. One-way ANOVA was used for intergroup comparison, Tukey's multiple comparison test was used for post-hoc comparisons.

Mentions: BrdU is incorporated into the DNA of proliferating NPCs. Thus, the appearance of BrdU immunoreactivity within a cell indicates that the cell was undergoing proliferation at the time upon BrdU was added. Using the BrdU-labeling method, we examined whether antidepressant-treated astrocytes could induce the proliferation of hippocampal NPCs, possibly through diffusible factors. To test this possibility, we used the Banker culture system, which does not allow direct contact between astrocytes and NPCs (Fig. 2A) [17]. The number of BrdU (+) cells was increased in NPCs co-cultured with naïve astrocytes (Fig. 2B; Control: 18.1% ± 0.9%, n = 12; naïve: 38.3% ± 4.6%, n = 10; p < 0.001). This result is consistent with previous findings [15]. However, in comparison with naïve astrocytes, the number of BrdU (+) cells was not further increased in NPCs co-cultured with astrocytes treated with 10 μM of desipramine or fluoxetine (Fig. 2B; Dep.: 31.2% ± 4.0%, n = 10; Flx.: 33.1% ± 3.6%, n = 10; p > 0.05, in comparison with the naïve group). Thus, these results show that the treatment of astrocytes with desipramine or fluoxetine may not affect the proliferation of NPCs via diffusible proliferating factors.


Null effect of antidepressants on the astrocytes-mediated proliferation of hippocampal progenitor cells in vitro.

Ko HG, Lee SJ, Son H, Kaang BK - Mol Pain (2007)

Effects of antidepressant-activated astrocytes on the proliferation of NPCs in a contact-independent culture system. (A) Proliferation of NPCs co-cultured with astrocytes using the Banker culture system. The astrocytes were not in contact with NPCs and could affect NPCs only through a diffusible factor. After BrdU immunocytochemical analysis, the nuclei were stained with DAPI (blue). An arrowhead (pink color) marks BrdU-labeled NPCs. Scale bar, 50 μm. (B) Quantification of the proliferation of NPCs. NPCs in control group were not exposed to astrocytes. In comparison with the control group, naïve astrocytes increased the number of BrdU (+) NPCs. However, in comparison with naïve astrocytes, those treated with 10 μM of desipramine or fluoxetine did not further increase the proliferation of NPCs (p > 0.05). Data shown are mean values ± SEM. One-way ANOVA was used for intergroup comparison, Tukey's multiple comparison test was used for post-hoc comparisons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1904438&req=5

Figure 2: Effects of antidepressant-activated astrocytes on the proliferation of NPCs in a contact-independent culture system. (A) Proliferation of NPCs co-cultured with astrocytes using the Banker culture system. The astrocytes were not in contact with NPCs and could affect NPCs only through a diffusible factor. After BrdU immunocytochemical analysis, the nuclei were stained with DAPI (blue). An arrowhead (pink color) marks BrdU-labeled NPCs. Scale bar, 50 μm. (B) Quantification of the proliferation of NPCs. NPCs in control group were not exposed to astrocytes. In comparison with the control group, naïve astrocytes increased the number of BrdU (+) NPCs. However, in comparison with naïve astrocytes, those treated with 10 μM of desipramine or fluoxetine did not further increase the proliferation of NPCs (p > 0.05). Data shown are mean values ± SEM. One-way ANOVA was used for intergroup comparison, Tukey's multiple comparison test was used for post-hoc comparisons.
Mentions: BrdU is incorporated into the DNA of proliferating NPCs. Thus, the appearance of BrdU immunoreactivity within a cell indicates that the cell was undergoing proliferation at the time upon BrdU was added. Using the BrdU-labeling method, we examined whether antidepressant-treated astrocytes could induce the proliferation of hippocampal NPCs, possibly through diffusible factors. To test this possibility, we used the Banker culture system, which does not allow direct contact between astrocytes and NPCs (Fig. 2A) [17]. The number of BrdU (+) cells was increased in NPCs co-cultured with naïve astrocytes (Fig. 2B; Control: 18.1% ± 0.9%, n = 12; naïve: 38.3% ± 4.6%, n = 10; p < 0.001). This result is consistent with previous findings [15]. However, in comparison with naïve astrocytes, the number of BrdU (+) cells was not further increased in NPCs co-cultured with astrocytes treated with 10 μM of desipramine or fluoxetine (Fig. 2B; Dep.: 31.2% ± 4.0%, n = 10; Flx.: 33.1% ± 3.6%, n = 10; p > 0.05, in comparison with the naïve group). Thus, these results show that the treatment of astrocytes with desipramine or fluoxetine may not affect the proliferation of NPCs via diffusible proliferating factors.

Bottom Line: The increase of neurogenesis might contribute to the behavioral effects of antidepressants.In both of these systems, in comparison with naïve astrocytes, antidepressant-treated astrocytes did not further increase the proliferation of NPCs.These results suggest that astrocytes increase the proliferation of hippocampal NPCs, however, this may not be directly involved in the antidepressant-induced proliferation of NPCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Creative Research Initiative Center for Memory and Institute of Molecular Biology and Genetics, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Gwanak-gu, Seoul, Korea. dhelix2@snu.ac.kr

ABSTRACT

Background: It is well known that antidepressants increase neurogenesis in the dentate gyrus of the hippocampus. The increase of neurogenesis might contribute to the behavioral effects of antidepressants. However, the mechanism by which antidepressants increase hippocampal neurogenesis is largely unknown. It has been recently reported that astroglia induce the neurogenesis of the hippocampal neural progenitor cells (NPCs). Therefore, we hypothesized that antidepressants may act on astrocytes, and this in turn induces neurogenesis of NPCs.

Results: To examine this hypothesis, we used two co-culture systems, i.e., a contact-independent Banker culture and a contact-dependent overlay co-culture. In both of these systems, in comparison with naïve astrocytes, antidepressant-treated astrocytes did not further increase the proliferation of NPCs.

Conclusion: These results suggest that astrocytes increase the proliferation of hippocampal NPCs, however, this may not be directly involved in the antidepressant-induced proliferation of NPCs.

Show MeSH
Related in: MedlinePlus