Sex-Related Motor Deficits in the Tau-P301L Mouse Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Behavioral Tests
2.2.1. Habituation/Dishabituation Olfactory Test
2.2.2. Nesting Behavior Test
2.2.3. Marble Burying Test
2.2.4. SHIRPA Test Battery
2.2.5. Open Field Test
2.2.6. Accelerating Rotarod
2.2.7. Modified Pole Test
2.2.8. Novel Object Recognition Test
2.2.9. T-Maze Spontaneous Alternation
2.2.10. Fear Conditioning Test
2.2.11. Morris Water Maze
2.3. Histology
2.4. Statistical Analysis
3. Results
3.1. Tau-P301L Male Mice Show Phenotypic Alterations Beginning at 4 Months of Age
3.2. Tau-P301L Male Mice Display Early Motor Deficits
3.3. Tau-P301L Show Mild Cognitive Deficits in the NOR
3.4. Tau-P301L Showed Distinct Tau Pathology in the Brain at 8 Months of Age
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | Description |
---|---|
Restlessness | Difficulty staying in one body position for an extended period of time |
Apathy | Motionless and lowered head |
Stereotyped behaviour | |
Convulsion | |
Abnormal body carriage | Body posture |
Alertness | Response to object proximity |
Abnormal gait | Uncommon walk, e.g., paddling, waddling, running |
Startle response | Response to an acoustic signal |
Loss of righting reflex | Time when the mouse return to standing position when turned on its back |
Touch response | |
Pinna reflex | |
Cornea reflex | |
Forelimb placing reflex | Response to stretch their front paws when hanged in proximity to the surface |
Hanging behaviour | Mouse stays on the rod or falls |
Pain response | Response to tail pinch |
Grooming | Overall fur condition |
Parameters | Phenotypic Alterations |
---|---|
Restlessness | No alterations |
Apathy | No alterations |
Stereotyped behavior | No alterations |
Convulsion | No alterations |
Abnormal body carriage | Hunchback |
Alertness | No alterations |
Abnormal gait | Waddling walk and slower compared to WT |
Startle response | No alterations |
Loss of righting reflex | Some Tau-P301L mice have light loss of righting reflex |
Touch response | Less responsive to touch than WT |
Pinna reflex | No alterations |
Cornea reflex | No alterations |
Forelimb placing reflex | Paralysis (“Clasping”) of the limbs |
Hanging behavior | Tau-P301L male mice fall faster from the rod than WT male mice |
Pain response | No alterations |
Grooming | The Tau-P301L male mice have very good fur condition compared to WT |
Staining | Brain Region | WT | Tau-P301L | Significance | ||
---|---|---|---|---|---|---|
Males | Females | Males | Females | |||
NeuN (Spot Count) | Hindbrain | 1434.7 ± 111.3 | 1307.6 ± 208.9 | 817.1 ± 181.7 | 1286.0 ± 246.4 | WT males vs. Tau-P301L males (p = 0.012) |
Midbrain | 1376.8 ± 184.5 | 1487.8 ± 108.9 | 1191.9± 139.9 | 1474.3 ± 237.6 | n.s | |
Cortex | 3545.1 ± 197.0 | 2879.1 ± 262.8 | 4141.1 ± 210.7 | 3651.3 ± 285.7 | n.s | |
Cerebellum | 1834.0 ± 83.6 | 1259.0 ± 123.5 | 2060.1 ± 158.2 | 1461.1 ± 187.0 | n.s | |
GFAP (Stained Area) | Hindbrain | 27.0 ± 1.0 | 29.3 ± 1.5 | 31.5 ± 3.6 | 33.4 ± 1.1 | n.s |
Midbrain | 18.6 ± 2.8 | 21.0 ± 3.3 | 19.9 ± 2.8 | 31.2 ± 2.1 | n.s | |
Cortex | 15.7 ± 2.7 | 23.4 ± 3.1 | 21.7 ± 4.4 | 31.8 ± 1.7 | n.s | |
Cerebellum | 8.5 ± 1.3 | 11.0 ± 1.8 | 11.8 ± 1.6 | 15.4 ± 1.0 | n.s | |
CD11b (Stained Area) | Hindbrain | 6.7 ± 0.9 | 5.6 ± 0.4 | 6.5 ± 0.6 | 5.7 ± 0.8 | n.s |
Midbrain | 6.0 ± 0.4 | 5.2 ± 0.6 | 5.5 ± 0.7 | 5.1 ± 0.5 | n.s | |
Cortex | 6.0 ± 0.5 | 5.9 ± 0.6 | 6.9 ± 0.9 | 6.0 ± 0.7 | n.s | |
Cerebellum | 6.5 ± 0.4 | 4.9 ± 0.7 | 6.6 ± 0.3 | 5.8 ± 0.3 | n.s |
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Camargo, L.C.; Honold, D.; Bauer, R.; Shah, N.J.; Langen, K.-J.; Willbold, D.; Kutzsche, J.; Willuweit, A.; Schemmert, S. Sex-Related Motor Deficits in the Tau-P301L Mouse Model. Biomedicines 2021, 9, 1160. https://doi.org/10.3390/biomedicines9091160
Camargo LC, Honold D, Bauer R, Shah NJ, Langen K-J, Willbold D, Kutzsche J, Willuweit A, Schemmert S. Sex-Related Motor Deficits in the Tau-P301L Mouse Model. Biomedicines. 2021; 9(9):1160. https://doi.org/10.3390/biomedicines9091160
Chicago/Turabian StyleCamargo, Luana Cristina, Dominik Honold, Robert Bauer, N. Jon Shah, Karl-Josef Langen, Dieter Willbold, Janine Kutzsche, Antje Willuweit, and Sarah Schemmert. 2021. "Sex-Related Motor Deficits in the Tau-P301L Mouse Model" Biomedicines 9, no. 9: 1160. https://doi.org/10.3390/biomedicines9091160