Established amyloid-β pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine
| Autor: | Athanasios Metaxas, Kate Lykke Lambertsen, Ove Wiborg, Elena V. Bouzinova, Maurizio Severino, Louise Ørum Olesen, Alicia A. Babcock, Asif Manzoor Khan, Jan Bert Gramsbergen, Bente Finsen, Christian Ulrich von Linstow, Mithula Sivasaravanaparan |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Serotonin Serotonin reuptake inhibitor Stereology Neocortex Transgenic mouse model Presenilin 03 medical and health sciences chemistry.chemical_compound [ H]DASB 0302 clinical medicine medicine Amyloid precursor protein [3H]DASB [H]DASB 5 7-Dihydroxytryptamine Serotonin transporter biology business.industry Cerebral amyloidosis Monoamine Featured Article Alzheimer's disease Paroxetine Selective serotonin reuptake inhibitor Psychiatry and Mental health 030104 developmental biology 5 7-dihydroxytryptamine chemistry biology.protein Antidepressant Autoradiography SERT occupancy Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Severino, M, Sivasaravanaparan, M, Olesen, L, von Linstow, C U, Metaxas, A, Bouzinova, E V, Khan, A M, Lambertsen, K L, Babcock, A A, Gramsbergen, J B, Wiborg, O & Finsen, B 2018, ' Established amyloid-β pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine ', Alzheimer's and Dementia: Translational Research and Clinical Interventions, vol. 4, pp. 215-223 . https://doi.org/10.1016/j.trci.2018.04.005 Severino, M, Sivasaravanaparan, M, Olesen, L Ø, von Linstow, C U, Metaxas, A, Bouzinova, E V, Khan, A M, Lambertsen, K L, Babcock, A A, Gramsbergen, J B, Wiborg, O & Finsen, B 2018, ' Established amyloid-β pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine ', Alzheimer's & Dementia, vol. 4, pp. 215-223 . https://doi.org/10.1016/j.trci.2018.04.005 Alzheimer's & Dementia : Translational Research & Clinical Interventions Severino, M, Sivasaravanaparan, M, Olesen, L Ø, von Linstow, C U, Metaxas, A, Bouzinova, E, Khan, A M, Lambertsen, K L, Babcock, A, Gramsbergen, J B, Wiborg, O & Finsen, B 2018, ' Established amyloid-β pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine ', Alzheimer's & Dementia: Translational Research & Clinical Interventions, vol. 4, pp. 215-223 . https://doi.org/10.1016/j.trci.2018.04.005 |
| DOI: | 10.1016/j.trci.2018.04.005 |
| Popis: | Introduction Treatment with selective serotonin reuptake inhibitors has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to an antidepressant mechanism of action. Methods We investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates Aβ pathology in plaque-bearing double-transgenic amyloid precursor protein (APP)swe/presenilin 1 (PS1)ΔE9 mutants. In addition, we addressed whether serotonin depletion affects Aβ pathology. Treatments were assessed by measurement of serotonin transporter occupancy and high-performance liquid chromatography. The effect of paroxetine on Aβ pathology was evaluated by stereological plaque load estimation and Aβ42/Aβ40 ratio by enzyme-linked immunosorbent assay. Results Contrary to our hypothesis, paroxetine therapy did not mitigate Aβ pathology, and depletion of brain serotonin did not exacerbate Aβ pathology. However, chronic paroxetine therapy increased mortality in APPswe/PS1ΔE9 transgenic mice. Discussion Our results question the ability of selective serotonin reuptake inhibitor therapy to ameliorate established Aβ pathology. The severe adverse effect of paroxetine may discourage its use for disease-modifying purposes in Alzheimer's disease. Highlights • Chronic paroxetine treatment does not mitigate established amyloid-β pathology in APPswe/PS1ΔE9 mice. • Chronic paroxetine treatment increases the mortality of APPswe/PS1ΔE9 but not littermate wild-type mice. • Serotonergic depletion does not influence established amyloid-β pathology in APPswe/PS1ΔE9 mice. |
| Databáze: | OpenAIRE |
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