Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Cognitive Tests
2.1.1. Morris Water Maze (MWM) Test
2.1.2. Social Discrimination (SD) Test
2.2. Tests of Anxiety-Like Behavior
2.2.1. Open Field (OF) Test
2.2.2. Elevated Plus Maze (EPM) Test
2.2.3. Light-Dark (LD) Test
2.2.4. Novelty Suppressed Feeding (NSF) Test
2.2.5. Social Interaction (SI) Test
2.3. Tests of Depressive-like Behavior
2.3.1. Forced Swim Test (FST)
2.3.2. Tail Suspension Test (TST)
2.3.3. Sucrose Preference Test (SPT)
2.3.4. Splash Test
2.3.5. Learned Helplessness (LH) Test
2.4. Acetylcholinesterase (AChE) Immunohistochemistry
2.5. Dexamethasone Suppression Test
3. Discussion
3.1. Cognitive Tests
3.2. Anxiety-like Behavior
3.3. Depression-like Behavior
3.4. Acetylcholinesterase (AChE) Immunohistochemistry
3.5. Dexamethasone Suppression
4. Materials and Methods
4.1. Animals
4.2. Behavioral Tests
4.2.1. Cognitive Tests
Morris Water Maze (MWM) Test
Social Discrimination (SD) Test
4.2.2. Tests of Anxiety-Like Behavior
Open Field (OF) Test
Elevated Plus Maze (EPM)
Light-Dark (LD) Test
Novelty Suppressed Feeding (NSF) Test
Social Interaction (SI) Test
4.2.3. Tests of Depression-like Behavior
Forced Swim Test (FST)
Tail Suspension Test (TST)
Splash Test
Sucrose Preference Test (SPT)
4.3. Immunohistochemistry
4.3.1. Cholinergic Fiber Labelling in the Somatosensory and Motor Cortex
4.3.2. Analysis of Histological Data
4.4. Dexamethasone Suppression Test
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Test | Main Finding in 3xTg-AD Mice Compared to Controls | Age of the Mice (Months) | Author(s) |
Morris Water Maze (MWM) | normal | 2 | [15] |
no learning and memory impairment, reduced cognitive flexibility, higher speed | 6 | [30] | |
no circadian variation in performance | [31] | ||
no proper control | [55] | ||
impaired performance | [56,57] | ||
no difference | 7 | [58] | |
learning impairment | 4 and 7 | [59] | |
learning impairment | 8 | [60] | |
longer swimming paths during learning | 10 and 17 | [61] | |
impaired performance | 10 10 | [62] | |
same learning curve | [63] | ||
Social discrimination test (SD) | no significant difference no proper control group | 6 | [17] [64] |
Open field (OF) | altered thigmotaxis with reduction of horizontal and vertical activities for 2 months | 2, 4 and 6 | [29] |
impaired locomotion | 3, 6, 9, 12 | [21] | |
no difference (4 m) less horizontal activity (7 m) | 4 and 7 | [59] | |
less movement | [30] | ||
more time to entering periphery | 6 | [37] | |
less time in the center and same distance travelled | [20] | ||
more freezing and bizarre behaviors | [65] | ||
less activity | 7 | [62] | |
less activity in both ages | 10 and 17 | [66] | |
less distance travel for all ages | 12 and 18 | [27] | |
less total distance walked | 12 | [29] | |
less rearing behaviors more time in the periphery | 18 | [67] | |
Elevated Plus Maze (EPM) | more time in the open arms | 3, 6, 9 and 12 | [21] |
decreased number of entries and less time spend in the open arms; no difference in the total distance travel | 6 | [20] | |
more latency to move | [37] | ||
less time spent in the open arms | 9 | [22] | |
no proper control | 18 | [68] | |
Light-dark box (LD) | less time spent entering and less distance traveled in the light compartment | 6 | [20] |
more freezing time in the light compartment | [57] | ||
more time in the light compartment lower latency in entering the dark | [65] | ||
more latency to enter the light compartment (7 m) | 4 and 7 | [59] | |
lower latency of stretch attendance (7 m) | 7 and 11 | [65] | |
same time spent in the light compartment frequency of changing compartments was lower | 20 | [23] | |
Novelty suppressed feeding (NSF) | no data available | - | - |
decreased social interaction | 9 | [24] | |
Social interaction (SI) | increased social interaction (18m) | 12 and 18 | [27] |
decreased social interaction | 12 and 14 | [25] | |
Forced swim test (FST) | more time immobile | 11 | [69] |
less time immobile and more time in swimming | 12 | [28] | |
more time immobile | 18 | [67] | |
Tail suspension test (TST) | more time spent in immobility | 18 | [67] |
Sucrose preference test (SPT) | decreased sucrose preference | 9 | [22] |
decreased sucrose preference | 18 | [67] | |
Splash test | no data available | - | - |
Learned helplessness (LH) | no data available | - | - |
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Test | Main Finding in 3xTg-AD Mice Compared to Controls | Interpretation |
---|---|---|
Morris water maze (MWM) | ↑ Latency to find the platform (8-m) | Progressive long-term memory loss |
Social discrimination (SD) | 3xTg-AD DI did not differ from 0 | Short-term memory impairment |
Open field (OF) | ↓ Time with active movement | Anxiety-like behavior |
Elevated plus maze (EPM) | - | - |
Light-dark box (LD) | ↓ Motivation to explore | Anxiety-like behavior |
Novelty suppressed feeding (NSF) | ↑ Immobility | Anxiety-like behavior |
Social interaction (SI) | ↓ Social behavior (8-m) | Progressive anxiety-like behavior |
Forced swim test (FST) | ↑ Swimming | Stress coping impairment? |
Tail suspension test (TST) | - | - |
Sucrose preference test (SPT) | - | - |
Splash | ↓ Grooming | Depression-like behavior |
Learned helplessness (LH) | ↓ Escape latency | Stress-coping impairment? |
Dexamethasone suppression | Non-suppression (4-m) | Depression-like behavior |
AChE immunohistochemistry in cortex | ↓ Fiber density (8-m) | Progressive fiber density decrease |
Test | 4-Month | 8-Month | ||
---|---|---|---|---|
3xTg-AD | Control | 3xTg-AD | Control | |
Morris Water Maze (MWM) | 8 | 8 | 6 | 8 |
Social discrimination (SD) | 8 | 8 | 6 | 8 |
Open field (OF) | 8 | 8 | 6 | 8 |
Elevated plus maze (EPM) | 10 | 11 | 8 | 8 |
Light-dark box (LD) | 11 | 10 | 7 | 12 |
Novelty suppressed feeding (NSF) | 8 | 10 | 10 | 14 |
Social interaction (SI) | 11 | 10 | 7 | 12 |
Forced swim test (FST) | 8 | 10 | 13 | 14 |
Tail suspension test (TST) | 9 | 10 | 14 | 14 |
Splash | 9 | 10 | 12 | 13 |
Sucrose preference test (SPT) | 9 | 10 | 14 | 14 |
Learned helplessness (LH) | 9 | 10 | 14 | 11 |
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Várkonyi, D.; Török, B.; Sipos, E.; Fazekas, C.L.; Bánrévi, K.; Correia, P.; Chaves, T.; Farkas, S.; Szabó, A.; Martínez-Bellver, S.; et al. Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 10816. https://doi.org/10.3390/ijms231810816
Várkonyi D, Török B, Sipos E, Fazekas CL, Bánrévi K, Correia P, Chaves T, Farkas S, Szabó A, Martínez-Bellver S, et al. Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer’s Disease. International Journal of Molecular Sciences. 2022; 23(18):10816. https://doi.org/10.3390/ijms231810816
Chicago/Turabian StyleVárkonyi, Dorottya, Bibiána Török, Eszter Sipos, Csilla Lea Fazekas, Krisztina Bánrévi, Pedro Correia, Tiago Chaves, Szidónia Farkas, Adrienn Szabó, Sergio Martínez-Bellver, and et al. 2022. "Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer’s Disease" International Journal of Molecular Sciences 23, no. 18: 10816. https://doi.org/10.3390/ijms231810816