Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common cause of dementia. Fingolimod has previously shown beneficial effects in different animal models of AD. However, it has shown contradictory effects when it has been applied at early disease stages. Our objective was to evaluate fingolimod in two different...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/13/2/331 |
| _version_ | 1797622093365379072 |
|---|---|
| author | Pablo Bascuñana Mirjam Brackhan Luisa Möhle Jingyun Wu Thomas Brüning Ivan Eiriz Baiba Jansone Jens Pahnke |
| author_facet | Pablo Bascuñana Mirjam Brackhan Luisa Möhle Jingyun Wu Thomas Brüning Ivan Eiriz Baiba Jansone Jens Pahnke |
| author_sort | Pablo Bascuñana |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common cause of dementia. Fingolimod has previously shown beneficial effects in different animal models of AD. However, it has shown contradictory effects when it has been applied at early disease stages. Our objective was to evaluate fingolimod in two different treatment paradigms. To address this aim, we treated male and female APP-transgenic mice for 50 days, starting either before plaque deposition at 50 days of age (early) or at 125 days of age (late). To evaluate the effects, we investigated the neuroinflammatory and glial markers, the Aβ load, and the concentration of the brain-derived neurotrophic factor (BDNF). We found a reduced Aβ load only in male animals in the late treatment paradigm. These animals also showed reduced microglia activation and reduced IL-1β. No other treatment group showed any difference in comparison to the controls. On the other hand, we detected a linear correlation between BDNF and the brain Aβ concentrations. The fingolimod treatment has shown beneficial effects in AD models, but the outcome depends on the neuroinflammatory state at the start of the treatment. Thus, according to our data, a fingolimod treatment would be effective after the onset of the first AD symptoms, mainly affecting the neuroinflammatory reaction to the ongoing Aβ deposition. |
| first_indexed | 2024-03-11T09:06:21Z |
| format | Article |
| id | doaj.art-d1485acc75c0483889a52eb3e8b18b7b |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T09:06:21Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d1485acc75c0483889a52eb3e8b18b7b2023-11-16T19:23:40ZengMDPI AGBiomolecules2218-273X2023-02-0113233110.3390/biom13020331Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s DiseasePablo Bascuñana0Mirjam Brackhan1Luisa Möhle2Jingyun Wu3Thomas Brüning4Ivan Eiriz5Baiba Jansone6Jens Pahnke7Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Pharmacology, Faculty of Medicine, University of Latvia, Jelgavas iela 3, 1004 Rīga, LatviaDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, NorwayAlzheimer’s disease (AD) is the most common cause of dementia. Fingolimod has previously shown beneficial effects in different animal models of AD. However, it has shown contradictory effects when it has been applied at early disease stages. Our objective was to evaluate fingolimod in two different treatment paradigms. To address this aim, we treated male and female APP-transgenic mice for 50 days, starting either before plaque deposition at 50 days of age (early) or at 125 days of age (late). To evaluate the effects, we investigated the neuroinflammatory and glial markers, the Aβ load, and the concentration of the brain-derived neurotrophic factor (BDNF). We found a reduced Aβ load only in male animals in the late treatment paradigm. These animals also showed reduced microglia activation and reduced IL-1β. No other treatment group showed any difference in comparison to the controls. On the other hand, we detected a linear correlation between BDNF and the brain Aβ concentrations. The fingolimod treatment has shown beneficial effects in AD models, but the outcome depends on the neuroinflammatory state at the start of the treatment. Thus, according to our data, a fingolimod treatment would be effective after the onset of the first AD symptoms, mainly affecting the neuroinflammatory reaction to the ongoing Aβ deposition.https://www.mdpi.com/2218-273X/13/2/331FTY720fingolimodGilenyaAPPPS1Alzheimer’s diseaseamyloid beta |
| spellingShingle | Pablo Bascuñana Mirjam Brackhan Luisa Möhle Jingyun Wu Thomas Brüning Ivan Eiriz Baiba Jansone Jens Pahnke Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s Disease Biomolecules FTY720 fingolimod Gilenya APPPS1 Alzheimer’s disease amyloid beta |
| title | Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s Disease |
| title_full | Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s Disease |
| title_fullStr | Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s Disease |
| title_full_unstemmed | Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s Disease |
| title_short | Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer’s Disease |
| title_sort | time and sex dependent effects of fingolimod treatment in a mouse model of alzheimer s disease |
| topic | FTY720 fingolimod Gilenya APPPS1 Alzheimer’s disease amyloid beta |
| url | https://www.mdpi.com/2218-273X/13/2/331 |
| work_keys_str_mv | AT pablobascunana timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease AT mirjambrackhan timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease AT luisamohle timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease AT jingyunwu timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease AT thomasbruning timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease AT ivaneiriz timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease AT baibajansone timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease AT jenspahnke timeandsexdependenteffectsoffingolimodtreatmentinamousemodelofalzheimersdisease |