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Results: 5

1.
Figure 5

Figure 5. Volume of granule cell layer.. From: Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates.

Two-way ANOVA with Bonferroni post-hoc comparisons showed a significant decrease in granule cell layer volumes of Stress-Placebo and Radiation-Stress-Drug groups when compared with control-placebo (p<0.01).

Tarique D. Perera, et al. PLoS One. 2011;6(4):e17600.
2.
Figure 2

Figure 2. Images of Doublecortin-expressing new neurons at different stages of maturation and BrdU-NeuN co-labeled cells.. From: Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates.

a. Doublecortin-expressing cells in the SGZ at different stages of maturation. Stage 1. Immature neurons that lack dendrites, or have short dendrites that lack branches. Stage 2. Differentiating neurons with dendrites that have secondary branches and extend no further than the inner molecular layer. Stage 3. Neurons with dendrites that have tertiary branches and extend into the outer molecular layer. b. Confocal image of BrdU-NeuN co-labeled cells. Stage 4 BrdU-labeled cells (green) that also express the mature neuronal marker NeuN (red) with the overlayed images of NeuN and BrdU labeling (yellow).

Tarique D. Perera, et al. PLoS One. 2011;6(4):e17600.
3.
Figure 1

Figure 1. Behavioral Results.. From: Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates.

a. Anhedonia scores. Anhedonia scores showed an effect of group (F4,65 = 5.6, p = 0.0001), time (F5,65 = 17.1, p<0.0001), group and time interaction (F20,65 = 3.4, p = 0.0001). Bonferroni post-hoc tests showed that Stress-Placebo and Radiation-Stress-Drug groups had greater anhedonia compared to Control-Drug, Control-Placebo, and Stress-Drug groups by 13–15 weeks (p<0.01). Error bars represent standard error of mean. b. Hierarchy scores in stressed subjects. Hierarchy (defined as the difference between dominance and subordinance scores) showed an interaction between group and time (F10, 35 = 2.1, p = 0.04). Bonferroni post-hoc tests showed that the Stress-Drug group had higher hierarchy scores compared to Stress-Placebo (p<0.01) and Radiation-Stress-Drug (p<0.05) by week 13–15. The controls showed no changes in hierarchy over the 15 weeks (Fig.S1). c. Affiliation scores in homecage. Affiliation (physical contact and huddling) showed an effect of group (F4, 65 = 4.1, p = 0.023) and time (F5, 65 = 2.6, p = 0.033) and a group by time interaction (F20, 65 = 2.4, p = 0.005). Bonferroni post-hoc tests showed that the stressed subjects (Stress-Placebo, Stress-Drug, and Radiation-Stress-Drug) had greater affiliation compared to non-stressed subjects (Control-Drug and Control-Placebo) (p<0.05) during most of weeks 1–15.

Tarique D. Perera, et al. PLoS One. 2011;6(4):e17600.
4.
Figure 4

Figure 4. a. Left panel: Precursor cell survival rates. BrdU-labeling represented proliferating hippocampal precursors that took up BrdU on week-7 and survived until sacrifice on week-15.. From: Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates.

Log10 transformed rates of BrdU-labeled cells in the SGZ did not show an effect of experimental group (F4,13 = 1.7, p = 0.46). b. Right panel: Precursor cell proliferation rates. Hippocampal cell proliferation rates at the time of sacrifice were identified by the expression of Ki67. Log10 transformed rates of Ki67 expressing cells showed an overall effect of group (F4,13 = 6.8, p<0.001) stemming from decreased counts in Stress-Placebo compared to all other groups per Bonferroni post-hoc tests (p<0.01). b Left panel: Maturational fate of BrdU-labeled cells on week 7. The percentage of BrdU-labeled cells that co-labeled with NeuN was designated as new neurons and BrdU-labeled cells that co-labeled with Iba-1 were designated as microglia. Two-way ANOVA showed an overall interaction between group and maturational stage (P<0.0001), as well as an effect of group (p = 0.036), and maturational fate (p<0.0001). Bonferroni post-hoc tests showed greater levels of BrdU-NeuN co-labeling (p<0.01) and lower levels of BrdU-Iba-1 co-labeling (P<0.001) in the 4 non-irradiated subjects (Control-Drug, Control-Placebo, Stress-Drug, and Stress-Placebo) compared to irradiated subjects (Radiation-Stress-Drug group).

Tarique D. Perera, et al. PLoS One. 2011;6(4):e17600.
5.
Figure 3

Figure 3. Neurogenesis rates.. From: Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates.

a. Neurogenesis rates based on maturational stage and regional distribution Neurogenesis rates at the three maturational stages were divided based on location in the anterior (left panel) or posterior (right panel) dentate gyrus. Multivariate analysis conducted on these six subdivisions showed an overall effect of experimental group (F4,5 = 90.01, p<0.0001). Univariate analysis of experimental group effects for each of the six sub-divisions of neurogenesis rates revealed significant effects only for Stage 3 neurons in the anterior dentate gyrus (F4,5 = 22.25, p<0.0001). Bonferroni post-hoc tests showed that only Stage 3 anterior dentate gyrus neurons were reduced in both depressive groups (Stress-Placebo and Stress-Drug-Radiation) compared to non-depressed groups (p<0.05). Data were Log10 transformed for statistical analysis to correct for uneven variance. b. Correlation between anhedonia scores and neurogenesis rates. Multiple regression analysis was conducted between anhedonia scores obtained at 5 different observation periods and the 6 subdivisions of neurogenesis rates. Anhedonia rates at the final observation period (weeks 13–15) inversely correlated only with Stage 3 anterior dentate gyrus neurons (r2 = 0.52, p<0.001). Since the regression curve appeared non-linear, a second degree polynomial fit was found to be the best (r2 = 0.67, p<0.0001). Anhedonia rates at weeks 10–12 inversely correlated with Stage 4 anterior dentate gyrus neurons (r2 = 0.28, p = 0.02). Likewise, a second-degree polynomial fit was found to be the best (r2 = 0.34, p<0.01).

Tarique D. Perera, et al. PLoS One. 2011;6(4):e17600.

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