Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice
The prevalence of Alzheimer’s disorder (AD) is increasing worldwide, and the co-morbid anxiety is an important, albeit often neglected problem, which might appear early during disease development. Animal models can be used to study this question. Mice, as prey animals, show an innate defensive respo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/262 |
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| author | Adrienn Szabó Szidónia Farkas Csilla Fazekas Pedro Correia Tiago Chaves Eszter Sipos Bernadett Makkai Bibiána Török Dóra Zelena |
| author_facet | Adrienn Szabó Szidónia Farkas Csilla Fazekas Pedro Correia Tiago Chaves Eszter Sipos Bernadett Makkai Bibiána Török Dóra Zelena |
| author_sort | Adrienn Szabó |
| collection | DOAJ |
| description | The prevalence of Alzheimer’s disorder (AD) is increasing worldwide, and the co-morbid anxiety is an important, albeit often neglected problem, which might appear early during disease development. Animal models can be used to study this question. Mice, as prey animals, show an innate defensive response against a predator odor, providing a valuable tool for anxiety research. Our aim was to test whether the triple-transgenic mice model of AD shows signs of innate anxiety, with specific focus on the temporal appearance of the symptoms. We compared 3xTg-AD mice bearing human mutations of amyloid precursor protein, presenilin 1, and tau with age-matched controls. First, separate age-groups (between 2 and 18 months) were tested for the avoidance of 2-methyl-2-thiazoline, a fox odor component. To test whether hypolocomotion is a general sign of innate anxiety, open-field behavior was subsequently followed monthly in both sexes. The 3xTg-AD mice showed more immobility, approached the fox odor container less often, and spent more time in the avoidance zone. This effect was detectable already in two-month-old animals irrespective of sex, not visible around six months of age, and was more pronounced in aged females than males. The 3xTg-AD animals moved generally less. They also spent less time in the center of the open-field, which was detectable mainly in females older than five months. In contrast to controls, the aged 3xTg-AD was not able to habituate to the arena during a 30-min observation period irrespective of their sex. Amyloid beta and phospho-Tau accumulated gradually in the hippocampus, amygdala, olfactory bulb, and piriform cortex. In conclusion, the early appearance of predator odor- and open space-induced innate anxiety detected already in two-month-old 3xTg-AD mice make this genetically predisposed strain a good model for testing anxiety both before the onset of AD-related symptoms as well as during the later phase. Synaptic dysfunction by protein deposits might contribute to these disturbances. |
| first_indexed | 2024-03-11T09:07:34Z |
| format | Article |
| id | doaj.art-9b091d755b83405abf53c710c06e4139 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:07:34Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-9b091d755b83405abf53c710c06e41392023-11-16T19:15:36ZengMDPI AGBiomedicines2227-90592023-01-0111226210.3390/biomedicines11020262Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model MiceAdrienn Szabó0Szidónia Farkas1Csilla Fazekas2Pedro Correia3Tiago Chaves4Eszter Sipos5Bernadett Makkai6Bibiána Török7Dóra Zelena8Centre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryCentre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryCentre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryCentre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryCentre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryLaboratory of Behavioral and Stress Studies, Institute of Experimental Medicine, 1083 Budapest, HungaryCentre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryCentre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryCentre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, HungaryThe prevalence of Alzheimer’s disorder (AD) is increasing worldwide, and the co-morbid anxiety is an important, albeit often neglected problem, which might appear early during disease development. Animal models can be used to study this question. Mice, as prey animals, show an innate defensive response against a predator odor, providing a valuable tool for anxiety research. Our aim was to test whether the triple-transgenic mice model of AD shows signs of innate anxiety, with specific focus on the temporal appearance of the symptoms. We compared 3xTg-AD mice bearing human mutations of amyloid precursor protein, presenilin 1, and tau with age-matched controls. First, separate age-groups (between 2 and 18 months) were tested for the avoidance of 2-methyl-2-thiazoline, a fox odor component. To test whether hypolocomotion is a general sign of innate anxiety, open-field behavior was subsequently followed monthly in both sexes. The 3xTg-AD mice showed more immobility, approached the fox odor container less often, and spent more time in the avoidance zone. This effect was detectable already in two-month-old animals irrespective of sex, not visible around six months of age, and was more pronounced in aged females than males. The 3xTg-AD animals moved generally less. They also spent less time in the center of the open-field, which was detectable mainly in females older than five months. In contrast to controls, the aged 3xTg-AD was not able to habituate to the arena during a 30-min observation period irrespective of their sex. Amyloid beta and phospho-Tau accumulated gradually in the hippocampus, amygdala, olfactory bulb, and piriform cortex. In conclusion, the early appearance of predator odor- and open space-induced innate anxiety detected already in two-month-old 3xTg-AD mice make this genetically predisposed strain a good model for testing anxiety both before the onset of AD-related symptoms as well as during the later phase. Synaptic dysfunction by protein deposits might contribute to these disturbances.https://www.mdpi.com/2227-9059/11/2/262Alzheimer’s disorder3xTg-AD miceanxietyfox odoropen-fieldamyloid beta |
| spellingShingle | Adrienn Szabó Szidónia Farkas Csilla Fazekas Pedro Correia Tiago Chaves Eszter Sipos Bernadett Makkai Bibiána Török Dóra Zelena Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice Biomedicines Alzheimer’s disorder 3xTg-AD mice anxiety fox odor open-field amyloid beta |
| title | Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice |
| title_full | Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice |
| title_fullStr | Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice |
| title_full_unstemmed | Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice |
| title_short | Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice |
| title_sort | temporal appearance of enhanced innate anxiety in alzheimer model mice |
| topic | Alzheimer’s disorder 3xTg-AD mice anxiety fox odor open-field amyloid beta |
| url | https://www.mdpi.com/2227-9059/11/2/262 |
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