Cells, Vol. 12, Pages 119: Fecal Microbiota Transplantation Reduces Pathology and Improves Cognition in a Mouse Model of Alzheimer’s Disease

Figure 1. Diagram showing treatment and numbers of healthy (WT) and transgenic mice undergoing FMT via oral gavage. Young Tg-FY: Young Transgenic-Fed Young, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old.

Figure 1. Diagram showing treatment and numbers of healthy (WT) and transgenic mice undergoing FMT via oral gavage. Young Tg-FY: Young Transgenic-Fed Young, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old.

Cells 12 00119 g001

Figure 2. FMT treated mice show normalization of behavior approaching control levels on the elevated plus maze. Old Tg-FY groups (n = 8) show improvement in anxiety-related behavior with increased (a) Percentage of time spent in closed arms and (b) Ratio of Closed:Open arm entries. Young Tg-FY group (n = 8) showed overall decreased anxiety with (c) a small increase in Percentage of time spent in closed arms and (d) decreased Ratio of Closed:Open arm entries. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 2. FMT treated mice show normalization of behavior approaching control levels on the elevated plus maze. Old Tg-FY groups (n = 8) show improvement in anxiety-related behavior with increased (a) Percentage of time spent in closed arms and (b) Ratio of Closed:Open arm entries. Young Tg-FY group (n = 8) showed overall decreased anxiety with (c) a small increase in Percentage of time spent in closed arms and (d) decreased Ratio of Closed:Open arm entries. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Cells 12 00119 g002aCells 12 00119 g002b

Figure 3. FMT treated mice show improved recognition and spatial memory levels in Novel Object Recognition test measured using Discrimination Index (DI). (a) Old Tg-FO (n = 8) and Old Tg-FY (n = 8) had increased Discrimination Index (Old Tg-FY p < 0.01 compared to Old Tg-Control (n = 7)). (b) Young Tg-FY also showed improved DI compared to Young Tg-Control (n = 8). WT values are presented for comparison only. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 3. FMT treated mice show improved recognition and spatial memory levels in Novel Object Recognition test measured using Discrimination Index (DI). (a) Old Tg-FO (n = 8) and Old Tg-FY (n = 8) had increased Discrimination Index (Old Tg-FY p < 0.01 compared to Old Tg-Control (n = 7)). (b) Young Tg-FY also showed improved DI compared to Young Tg-Control (n = 8). WT values are presented for comparison only. Data is presented as mean ± SEM. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Cells 12 00119 g003

Figure 4. Spatial memory levels improved in Old treated mice in Forced Alternation Y-maze. Data is presented as mean ± SEM. Old Tg-FO (n = 8) and Old Tg-FY (n = 8) demonstrated increased (a) exploration time in Novel arm and (b) Ratio of Novel to Open arm entries (p < 0.05 compared to Old Tg-Control (n = 7)). (c,d) Young Tg-FY (n = 8) did not show improvement in FAY compared to Young Tg-Control (n = 7). WT values are presented for comparison only. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Figure 4. Spatial memory levels improved in Old treated mice in Forced Alternation Y-maze. Data is presented as mean ± SEM. Old Tg-FO (n = 8) and Old Tg-FY (n = 8) demonstrated increased (a) exploration time in Novel arm and (b) Ratio of Novel to Open arm entries (p < 0.05 compared to Old Tg-Control (n = 7)). (c,d) Young Tg-FY (n = 8) did not show improvement in FAY compared to Young Tg-Control (n = 7). WT values are presented for comparison only. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control, Young WT: Young Wildtype, Old WT: Old Wildtype.

Cells 12 00119 g004aCells 12 00119 g004b

Figure 5. FMT resulted in decreased amyloid plaque burden in treated mice as seen in Thioflavin S—stained brain sections. (a) Old Tg-FO and Old Tg-FY both had reduced percentage amyloid plaque with a nearly 2-fold decrease in Old Tg-FO (p < 0.01) and Old Tg-FY mice (p < 0.01) as well as (b) fewer plaques in both groups of treated mice (Old Tg-FY p < 0.05). (c) Young Tg-FY mice also showed a reduced percentage area of amyloid plaques with (d) no difference seen in the number of plaques. (e) Old Tg-FY mice showed decreased numbers of varying plaque sizes as compared to both Old Tg-Control and Old Tg-FO while (f) Young Tg-FY also showed decreased numbers of all plaque sizes compared to Young Tg-Controls. (h) Old Tg-FO mice and (i) Old Tg-FY had lesser amyloid plaque burden compared to (g) Old Tg-Controls. Mature, compact plaques were more diffuse with less defined outlines following FMT. Although (k) Young Tg-FY mice did not demonstrate decreased plaque burden compared to (j) Young Tg-Control mice, plaque dispersal appeared similar to the Old treated mice. Data is presented as mean ± SEM. Scale bar = 50 μm. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Figure 5. FMT resulted in decreased amyloid plaque burden in treated mice as seen in Thioflavin S—stained brain sections. (a) Old Tg-FO and Old Tg-FY both had reduced percentage amyloid plaque with a nearly 2-fold decrease in Old Tg-FO (p < 0.01) and Old Tg-FY mice (p < 0.01) as well as (b) fewer plaques in both groups of treated mice (Old Tg-FY p < 0.05). (c) Young Tg-FY mice also showed a reduced percentage area of amyloid plaques with (d) no difference seen in the number of plaques. (e) Old Tg-FY mice showed decreased numbers of varying plaque sizes as compared to both Old Tg-Control and Old Tg-FO while (f) Young Tg-FY also showed decreased numbers of all plaque sizes compared to Young Tg-Controls. (h) Old Tg-FO mice and (i) Old Tg-FY had lesser amyloid plaque burden compared to (g) Old Tg-Controls. Mature, compact plaques were more diffuse with less defined outlines following FMT. Although (k) Young Tg-FY mice did not demonstrate decreased plaque burden compared to (j) Young Tg-Control mice, plaque dispersal appeared similar to the Old treated mice. Data is presented as mean ± SEM. Scale bar = 50 μm. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Cells 12 00119 g005aCells 12 00119 g005b

Figure 6. Cognition score based on behavioral study results compared to amyloid plaque burden shows donor age-dependent differences between treated mice groups. (a) Mice receiving fecal transplants from younger donors (Old Tg-FY) had higher cognition scores that correlated with lower amyloid loading compared to Old Tg-FO mice that received transplants from age-matched donors. (b) Young Tg-FY mice showed marginal decreases in amyloid load following treatment. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Figure 6. Cognition score based on behavioral study results compared to amyloid plaque burden shows donor age-dependent differences between treated mice groups. (a) Mice receiving fecal transplants from younger donors (Old Tg-FY) had higher cognition scores that correlated with lower amyloid loading compared to Old Tg-FO mice that received transplants from age-matched donors. (b) Young Tg-FY mice showed marginal decreases in amyloid load following treatment. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, Old Tg-Control: Old Transgenic Control.

Cells 12 00119 g006

Table 1. Summary of difference in significance across experimental groups for behavioral studies experimental measures and Aβ loading. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, EPM: Elevated Plus Maze, NOR: Novel Object Recognition, FAY: Forced Alternation Y-maze.

Table 1. Summary of difference in significance across experimental groups for behavioral studies experimental measures and Aβ loading. Young Tg-FY: Young Transgenic-Fed Young, Young Tg-Control: Young Transgenic Control, Old Tg-FY: Old Transgenic-Fed Young, Old Tg-FO: Old Transgenic-Fed Old, EPM: Elevated Plus Maze, NOR: Novel Object Recognition, FAY: Forced Alternation Y-maze.

Experimental MeasureOld Tg-FOOld Tg-FYYoung Tg-FYEPMp = 0.687p = 0.056p = 0.470NORp = 0.065p = 0.002p = 0.409FAYp = 0.046p = 0.012p = 0.505Aβ (amyloid load;
plaque number)p = 0.010;
p = 0.060p = 0.010;
p = 0.045p = 0.359

留言 (0)

沒有登入
gif