PMC

Figure A illustrates drawings of representative neurons from the control and PCMS groups using Neurolucida. Scale bar = 50μm. ML, Molecular layer. The bar charts (B-D) compare the total dendritic length (B), numbers of dendritic nodes (C), and numbers of dendritic endings (D) of relatively mature DCX+ newly born neurons between control rats and rats treated with predictable chronic mild stress (PCMS). Note that, newly born neurons from the PCMS treated group exhibit considerably higher values for all parameters of the dendritic growth.

Distribution of newly born neurons expressing doublecortin (DCX) in the subgranular zone-granule cell layer (SGZ-GCL) of hippocampi from an age-matched control rat (A1, A2) and a rat that underwent predictable chronic mild stress for 28 days (B1, B2). Scale bar, A1, B1 = 200 μm; A2, B2 = 50 μm; SGZ-GCL to adult rats. DH, dentate hilus; ML, molecular layer. The bar chart in Figure C1 compares the total numbers of DCX+ neurons (depicting the overall status of neurogenesis) in the SGZ-GCL between control rats (n=6) and rats that underwent PCMS (n=6). Values represent means and standard errors of the mean. Note that, the PCMS group exhibits significantly greater numbers of newly born neurons than the control group.

The bar charts A & B illustrate the results of forced swim test (FST) at one day (A) and 2 months (B) after the predictable chronic mild stress (PCMS) regimen. Note that, rats that underwent PCMS spend considerably reduced time in immobility (or floating), in comparison to the age-matched control rats that underwent handling alone at both early and extended time-points after PCMS. Reduced immobility time is an indication of reduced depressive-like behavior in the PCMS treated rats at both time-points. The bar charts C-F illustrate the results of elevated plus maze (EPM) test at 2 day (C, D) and 2 months (E, F) after the predictable chronic mild stress (PCMS) regimen. Note that, rats that underwent PCMS exhibit greater numbers of entries into the open arm and spend considerably greater time in the open arm, in comparison to the age-matched control rats that underwent handling alone at both early (C, D) and extended (E, F) time-points after PCMS. Reduced immobility time is an indication of reduced depressive-like behavior in PCMS treated rats at both time-points. The number of entries and time spent in open arms were used as indices of anxiety like behavior.

Figures A-B illustrate data pertaining to learning in the water maze test (WMT) between control and PCMS treated groups. Note that, both groups exhibited excellent spatial learning ability, as evidenced by progressive decreases in the latency to reach the platform over 7 sessions and similar r² values (A), and >80% reduction in the latency to reach the platform between the first and last sessions of learning (B). Figures C-F compare the results of probe (memory retention) test performed at 24 hrs after the last learning session between control and PCMS treated groups. Note that all parameters of the memory retention (latency to reach the platform area, dwell time in platform area, platform area crossings and dwell time in the platform quadrant) in the PCMS treated group are superior to the control group. The bar charts G-I compare the control and PCMS treated groups for the time spent with: (i) the familiar object (G); (ii) the novel object (H); and (iii) both familiar and novel objects (i.e. total exploration time; I). The bar chart in J illustrates the discrimination index for the novel object in both groups. Note that, in rats treated with PCMS, both time spent with the novel object (H) and the discrimination index for the novel object (J) are significantly greater than in age-matched control rats, which are suggestive of a superior memory function in the PCMS treated rats.

Representative photomicrographs depicting the distribution of newly born cells (i.e. BrdU+ cells) in the subgranular zone-granule cell layer (SGZ-GCL) of hippocampi from an age-matched control rat (A1, A2) and a rat that underwent predictable chronic mild stress for 28 days (B1, B2). Scale bar, A1, B1 = 200 μm; A2, B2 = 50 μm; DH, dentate hilus. Figure C1 compares the total numbers of newly born cells generated per day in the SGZ-GCL between control rats (n=6) and rats that underwent PCMS (n=6). Values represent means and standard errors of the mean. Note that, PCMS group exhibits significantly greater numbers of newly born cells than the control group. Figures D1-D3 illustrate newly born cells (i.e. the BrdU+ cells shown in green color) expressing doublecortin (DCX, red color) in the subgranular zone-granule cell layer of a rat treated with PCMS, visualized through BrdU-DCX dual immunofluorescence and Z-section analyses using a laser confocal microscope. Figure D4 shows an orthogonal view of a newly born cell expressing BrdU and DCX. Figure E1 shows percentages of newly born cells that differentiate into DCX+ neurons in the control and PCMS treated groups. Note that, the neuronal fate choice decision is similar between the two groups. Figure F1 illustrates the net neurogenesis based on the total numbers of BrdU+ cells and percentages of BrdU+ cells expressing DCX. The net neurogenesis is much greater in the PCMS group, in comparison to the control group.