Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer’s Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation
Abstract
:1. Introduction
2. Material and Methods
2.1. ScFv-h3D6 Production
2.2. Animals
2.3. Experimental Design
2.4. Sample Collection and Processing
2.5. Immunohistochemistry
2.6. Image Capture and Processing
2.7. Behavioral and Cognitive Tests
3. Results
3.1. Progression of BPSD-Like Symptoms
3.2. Effect of Cognitive Stimulation in Spatial Learning and Memory
3.3. Reversal Learning and Memory and Their Evolution
3.4. Effects of Chronic Immunotherapy in 3xTg-AD Mice
3.5. 3xTg-AD Mice Exhibit Evident Amyloid and Tau Pathologies at 9 Months of Age
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
3xTg-AD | triple-transgenic mouse model of AD |
AD | Alzheimer’s disease |
BPSD | behavioral and psychological symptoms of dementia |
CT | corner test |
MWM | Morris Water Maze |
NTg | non-transgenic |
OFT | open-field test |
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Corner Test | NTg | PBS-Treated 3xTg-AD | ScFv-h3D6-Treated 3xTg-AD |
---|---|---|---|
Horizontal activity | |||
Distance traveled (m) | |||
5-month-old | 1.53 ± 0.14 | 1.90 ± 0.15 #A | 2.29 ± 0.20 **A |
7-month-old | 0.96 ± 0.06 | 0.51 ± 0.11 **A | 0.56 ± 0.16 *A |
9-month-old | 0.50 ± 0.13 | 0.49 ± 0.16 | 0.49 ± 0.13 |
Corner visits (n) | |||
5-month-old | 11.00 ± 0.68 | 10.80 ± 0.77 | 12.10 ± 1.08 |
7-month-old | 6.50 ± 0.37 | 2.4 ± 0.69 ****A | 3.10 ± 0.88 **A |
9-month-old | 5.20 ± 0.85 | 2.63 ± 0.58 *A | 2.70 ± 0.65 *A |
Corner latency (s) | |||
5-month-old | 3.37 ± 0.63 | 1.76 ± 0.75 | 1.15 ± 0.41 **A |
7-month-old | 1.95 ± 0.43 | 10.67 ± 3.64 *A | 10.67 ± 3.77 *A |
9-month-old | 1.94 ± 0.67 | 5.50 ± 2.43 | 4.88 ± 2.39 |
Time in the corner (s) | |||
5-month-old | 10.56 ± 0.66 | 10.25 ± 1.12 | 9.26 ± 1.17 |
7-month-old | 10.52 ± 1.08 | 5.99 ± 1.78 *A | 4.70 ± 1.43 **A |
9-month-old | 9.08 ± 1.77 | 8.20 ± 2.93 | 7.71 ± 1.86 |
Vertical activity | |||
Rearings (n) | |||
5-month-old | 4.15 ± 0.49 | 4.20 ± 0.51 | 3.70 ± 0.83 |
7-month-old | 4.00 ± 0.45 | 2.67 ± 1.01 | 1.00 ± 0.33 ****A |
9-month-old | 2.80 ± 0.89 | 0.38 ± 0.24 *A | 0.40 ± 0.16 *A |
1st rearing latency (s) | |||
5-month-old | 0.13 ± 0.02 | 0.13 ± 0.02 | 0.12 ±0.03 |
7-month-old | 7.30 ± 1.24 | 18.00 ± 3.72 *A | 23.00 ± 2.53 ****A |
9-month-old | 12.30 ± 3.18 | 25.88 ± 2.43 **A | 25.40 ± 2.76 **A |
Other emotional behaviors | |||
Immobility time (s) | |||
5-month-old | 0.92 ± 0.50 | 0.65 ± 0.43 | 0.53 ± 0.35 |
7-month-old | 6.06 ± 1.30 | 17.18 ± 2.00 ***A | 18.54 ± 3.21 **A |
9-month-old | 12.73 ± 2.75 | 20.59 ± 2.50 *A | 22.06 ± 1.46 **A |
Defecations (boli) | |||
5-month-old | 0.40 ± 0.22 | 0.30 ± 0.21 | 0.20 ± 0.13 |
7-month-old | 1.00 ± 0.26 | 0.56 ± 0.28 | 0.50 ± 0.22 |
9-month-old | 0.80 ± 0.20 | 0.25 ± 0.15 #A | 0.00 ± 0.00 ***A,#B |
Open-Field Test | NTg | PBS-Treated 3xTg-AD | ScFv-h3D6-Treated 3xTg-AD |
---|---|---|---|
Horizontal activity | |||
Total distance traveled (m) | |||
5-month-old | 46.87 ± 3.54 | 19.36 ± 2.79 ****A | 24.30 ± 2.88 ***A |
7-month-old | 22.49 ± 2.88 | 12.94 ± 3.75 #A | 9.23 ± 1.82 **A |
9-month-old | 17.54 ± 3.07 | 10.43 ± 2.05 *A | 12.74 ± 2.75 |
Entries to the center (n) | |||
5-month-old | 41.70 ± 5.32 | 23.50 ± 4.92 *A | 26.60 ± 5.73 #A |
7-month-old | 22.00 ± 2.77 | 13.20 ± 4.86 | 12.3 ± 3.81 #A |
9-month-old | 15.6 ± 2.76 | 15.25 ± 4.64 | 14.10 ± 4.29 |
Distance in the center (m) | |||
5-month-old | 6.61 ± 0.58 | 3.68 ± 0.73 **A | 4.02 ± 0.88 *A |
7-month-old | 2.85 ± 0.45 | 2.10 ± 0.82 | 1.57 ± 0.52 #A |
9-month-old | 1.93 ± 0.31 | 1.58 ± 0.45 | 1.91 ± 0.58 |
Distance in the periphery (m) | |||
5-month-old | 40.26 ± 3.08 | 15.49 ± 2.20 ****A | 20.29 ± 2.34 ****A |
7-month-old | 19.65 ± 2.52 | 10.83 ± 3.06 *A | 7.66 ± 1.32 **A |
9-month-old | 15.61 ± 2.82 | 8.86 ± 1.61 *A | 10.84 ± 2.22 |
Ratio center/periphery (dist) | |||
5-month-old | 0.17 ± 0.01 | 0.24 ± 0.04 | 0.20 ± 0.03 |
7-month-old | 0.15 ± 0.01 | 0.23 ± 0.05 | 0.17 ± 0.03 |
9-month-old | 0.13 ± 0.02 | 0.15 ± 0.03 | 0.16 ± 0.03 |
Time in the center (s) | |||
5-month-old | 76.75 ± 9.03 | 93.07 ± 23.87 | 75.20 ± 17.30 |
7-month-old | 50.66 ± 7.40 | 159.5 ± 46.4 *A | 52.46 ± 17.91 *B |
9-month-old | 38.99 ± 7.74 | 57.98 ± 25.95 | 68.30 ± 23.00 |
Time in the periphery (s) | |||
5-month-old | 823.3 ± 9.04 | 723.2 ± 78.2 | 824.7 ± 17.3 |
7-month-old | 849.3 ± 7.39 | 740.2 ± 46.34 *A | 847.5 ± 17.9 *B |
9-month-old | 861.01 ± 7.73 | 841.98 ± 25.94 | 831.7 ± 23.0 |
Ratio center/periphery (time) | |||
5-month-old | 0.09 ± 0.01 | 0.15 ± 0.04 | 0.10 ± 0.02 |
7-month-old | 0.06 ± 0.01 | 0.27 ± 0.10 #A | 0.07 ± 0.02 #B |
9-month-old | 0.05 ± 0.01 | 0.08 ± 0.04 | 0.09 ± 0.03 |
Vertical activity | |||
Rearings (n) | |||
5-month-old | 73.20 ± 6.28 | 14.78 ± 3.22 ****A | 14.50 ± 2.25 ****A |
7-month-old | 35.60 ± 7.26 | 6.60 ± 1.75 **A | 3.80 ± 0.89 ***A |
9-month-old | 26.50 ± 6.36 | 3.57 ± 1.09 **A | 5.10 ± 1.33 **A |
1st rearing latency (s) | |||
5-month-old | 18.70 ± 3.10 | 64.89 ± 13.50 **A | 54.40 ± 14.48 ***A |
7-month-old | 18.20 ± 4.36 | 360.9 ± 124.8 *A | 243.3 ± 57.1 ****A |
9-month-old | 123.4 ± 87.7 | 269.1 ± 48.9 | 314.9 ± 105.1 |
Other emotional behaviors | |||
Immobility time (s) | |||
5-month-old | 116.8 ± 38.44 | 304.95 ± 84.19 #A | 215.27 ± 88.67 |
7-month-old | 229.41 ± 80.38 | 459.06 ± 107.27 | 310.07 ± 127.14 |
9-month-old | 364.31 ± 108.38 | 285.86 ± 125.45 | 525.6 ± 115.84 |
Self-groomings (n) | |||
5-month-old | 4.30 ± 0.34 | 3.33 ± 0.73 | 2.90 ± 1.06 |
7-month-old | 3.90 ± 1.14 | 3.40 ± 0.75 | 2.40 ± 0.7 |
9-month-old | 5.10 ± 0.74 | 3.50 ± 0.54 | 3.10 ± 0.38 *A |
Self-groomings latency (s) | |||
5-month-old | 148.4 ± 39.3 | 265.4 ± 31.8 *A | 343.0 ± 98.8 #A |
7-month-old | 276.5 ± 71.1 | 381.7 ± 77.9 | 402.3 ± 94.1 |
9-month-old | 80.20 ± 12.76 | 177.4 ± 35.2 *A | 201.9 ± 32.0 **A |
Time on self-grooming (s) | |||
5-month-old | 7.20 ± 0.98 | 5.24 ± 0.95 | 6.07 ± 2.31 |
7-month-old | 7.35 ± 1.93 | 6.15 ± 1.63 | 5.10 ± 1.42 |
9-month-old | 8.77 ± 1.42 | 7.46 ± 0.94 | 7.05 ± 0.77 |
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Roda, A.R.; Esquerda-Canals, G.; Martí-Clúa, J.; Villegas, S. Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer’s Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation. Pharmaceutics 2020, 12, 944. https://doi.org/10.3390/pharmaceutics12100944
Roda AR, Esquerda-Canals G, Martí-Clúa J, Villegas S. Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer’s Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation. Pharmaceutics. 2020; 12(10):944. https://doi.org/10.3390/pharmaceutics12100944
Chicago/Turabian StyleRoda, Alejandro R., Gisela Esquerda-Canals, Joaquim Martí-Clúa, and Sandra Villegas. 2020. "Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer’s Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation" Pharmaceutics 12, no. 10: 944. https://doi.org/10.3390/pharmaceutics12100944
APA StyleRoda, A. R., Esquerda-Canals, G., Martí-Clúa, J., & Villegas, S. (2020). Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer’s Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation. Pharmaceutics, 12(10), 944. https://doi.org/10.3390/pharmaceutics12100944