Aarhus Universitets segl

Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice. / Sivasaravanaparan, Mithula; Olesen, Louise Ørum; Severino, Maurizio et al.

I: Journal of Alzheimer's Disease, Bind 87, Nr. 2, 05.2022, s. 685-699.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Sivasaravanaparan, M, Olesen, LØ, Severino, M, Von Linstow, CU, Lambertsen, KL, Gramsbergen, JB, Hasselstrøm, J, Metaxas, A, Wiborg, O & Finsen, B 2022, 'Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice', Journal of Alzheimer's Disease, bind 87, nr. 2, s. 685-699. https://doi.org/10.3233/JAD-220019

APA

Sivasaravanaparan, M., Olesen, L. Ø., Severino, M., Von Linstow, C. U., Lambertsen, K. L., Gramsbergen, J. B., Hasselstrøm, J., Metaxas, A., Wiborg, O., & Finsen, B. (2022). Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice. Journal of Alzheimer's Disease, 87(2), 685-699. https://doi.org/10.3233/JAD-220019

CBE

Sivasaravanaparan M, Olesen LØ, Severino M, Von Linstow CU, Lambertsen KL, Gramsbergen JB, Hasselstrøm J, Metaxas A, Wiborg O, Finsen B. 2022. Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice. Journal of Alzheimer's Disease. 87(2):685-699. https://doi.org/10.3233/JAD-220019

MLA

Vancouver

Sivasaravanaparan M, Olesen LØ, Severino M, Von Linstow CU, Lambertsen KL, Gramsbergen JB et al. Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice. Journal of Alzheimer's Disease. 2022 maj;87(2):685-699. doi: 10.3233/JAD-220019

Author

Sivasaravanaparan, Mithula ; Olesen, Louise Ørum ; Severino, Maurizio et al. / Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice. I: Journal of Alzheimer's Disease. 2022 ; Bind 87, Nr. 2. s. 685-699.

Bibtex

@article{4c7ed35595cf447ba7a253f4e9852e7b,
title = "Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice",
abstract = "Background: Modulation of serotonergic signaling by treatment with selective serotonin reuptake inhibitors (SSRIs) has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to exerting an anti-depressant action. Objective: To investigate the efficacy of chronic treatment with the SSRI paroxetine, in mitigating Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of 18-month-old APPswe/PS1ΔE9 mice. Methods: Plaque-bearing APPswe/PS1ΔE9 and wildtype mice were treated with paroxetine per os at a dose of 5 mg/kg/day, from 9 to 18 months of age. The per os treatment was monitored by recording of the body weights and serum paroxetine concentrations, and by assessment of the serotonin transporter occupancy by [3H]DASB-binding in wildtype mice. Additionally, 5,7-dihydroxytryptamine was administered to 9-month-old APPswe/PS1ΔE9 mice, to examine the effect of serotonin depletion on Aβ pathology. Aβ pathology was evaluated by Aβ plaque load estimation and the Aβ42/Aβ40 ratio by ELISA. Results: Paroxetine treatment led to > 80% serotonin transporter occupancy. The treatment increased the body weight of wildtype mice, but not of APPswe/PS1ΔE9 mice. The treatment had no effect on the Aβ plaque load (p = 0.39), the number and size of plaques, or the Aβ plaque-induced increases in microglial numbers in the dentate gyrus. Three months of serotonin depletion did not significantly impact the Aβ plaque load or Aβ42/Aβ40 ratio in APPswe/PS1ΔE9 mice at 12 months. Conclusion: Our results show that chronic treatment with the SSRI paroxetine does not mitigate Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of APPswe/PS1ΔE9 mice.",
keywords = "Cerebral amyloidosis, chronic paroxetine treatment, hippocampus, microgliosis, neurogenesis, serotonin selective reuptake inhibitors, serotonin transporter occupancy, stereology, Y-maze",
author = "Mithula Sivasaravanaparan and Olesen, {Louise {\O}rum} and Maurizio Severino and {Von Linstow}, {Christian Ulrich} and Lambertsen, {Kate Lykke} and Gramsbergen, {Jan Bert} and J{\o}rgen Hasselstr{\o}m and Athanasios Metaxas and Ove Wiborg and Bente Finsen",
note = "Publisher Copyright: {\textcopyright} 2022 - IOS Press. All rights reserved.",
year = "2022",
month = may,
doi = "10.3233/JAD-220019",
language = "English",
volume = "87",
pages = "685--699",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "I O S Press",
number = "2",

}

RIS

TY - JOUR

T1 - Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice

AU - Sivasaravanaparan, Mithula

AU - Olesen, Louise Ørum

AU - Severino, Maurizio

AU - Von Linstow, Christian Ulrich

AU - Lambertsen, Kate Lykke

AU - Gramsbergen, Jan Bert

AU - Hasselstrøm, Jørgen

AU - Metaxas, Athanasios

AU - Wiborg, Ove

AU - Finsen, Bente

N1 - Publisher Copyright: © 2022 - IOS Press. All rights reserved.

PY - 2022/5

Y1 - 2022/5

N2 - Background: Modulation of serotonergic signaling by treatment with selective serotonin reuptake inhibitors (SSRIs) has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to exerting an anti-depressant action. Objective: To investigate the efficacy of chronic treatment with the SSRI paroxetine, in mitigating Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of 18-month-old APPswe/PS1ΔE9 mice. Methods: Plaque-bearing APPswe/PS1ΔE9 and wildtype mice were treated with paroxetine per os at a dose of 5 mg/kg/day, from 9 to 18 months of age. The per os treatment was monitored by recording of the body weights and serum paroxetine concentrations, and by assessment of the serotonin transporter occupancy by [3H]DASB-binding in wildtype mice. Additionally, 5,7-dihydroxytryptamine was administered to 9-month-old APPswe/PS1ΔE9 mice, to examine the effect of serotonin depletion on Aβ pathology. Aβ pathology was evaluated by Aβ plaque load estimation and the Aβ42/Aβ40 ratio by ELISA. Results: Paroxetine treatment led to > 80% serotonin transporter occupancy. The treatment increased the body weight of wildtype mice, but not of APPswe/PS1ΔE9 mice. The treatment had no effect on the Aβ plaque load (p = 0.39), the number and size of plaques, or the Aβ plaque-induced increases in microglial numbers in the dentate gyrus. Three months of serotonin depletion did not significantly impact the Aβ plaque load or Aβ42/Aβ40 ratio in APPswe/PS1ΔE9 mice at 12 months. Conclusion: Our results show that chronic treatment with the SSRI paroxetine does not mitigate Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of APPswe/PS1ΔE9 mice.

AB - Background: Modulation of serotonergic signaling by treatment with selective serotonin reuptake inhibitors (SSRIs) has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to exerting an anti-depressant action. Objective: To investigate the efficacy of chronic treatment with the SSRI paroxetine, in mitigating Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of 18-month-old APPswe/PS1ΔE9 mice. Methods: Plaque-bearing APPswe/PS1ΔE9 and wildtype mice were treated with paroxetine per os at a dose of 5 mg/kg/day, from 9 to 18 months of age. The per os treatment was monitored by recording of the body weights and serum paroxetine concentrations, and by assessment of the serotonin transporter occupancy by [3H]DASB-binding in wildtype mice. Additionally, 5,7-dihydroxytryptamine was administered to 9-month-old APPswe/PS1ΔE9 mice, to examine the effect of serotonin depletion on Aβ pathology. Aβ pathology was evaluated by Aβ plaque load estimation and the Aβ42/Aβ40 ratio by ELISA. Results: Paroxetine treatment led to > 80% serotonin transporter occupancy. The treatment increased the body weight of wildtype mice, but not of APPswe/PS1ΔE9 mice. The treatment had no effect on the Aβ plaque load (p = 0.39), the number and size of plaques, or the Aβ plaque-induced increases in microglial numbers in the dentate gyrus. Three months of serotonin depletion did not significantly impact the Aβ plaque load or Aβ42/Aβ40 ratio in APPswe/PS1ΔE9 mice at 12 months. Conclusion: Our results show that chronic treatment with the SSRI paroxetine does not mitigate Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of APPswe/PS1ΔE9 mice.

KW - Cerebral amyloidosis

KW - chronic paroxetine treatment

KW - hippocampus

KW - microgliosis

KW - neurogenesis

KW - serotonin selective reuptake inhibitors

KW - serotonin transporter occupancy

KW - stereology

KW - Y-maze

UR - http://www.scopus.com/inward/record.url?scp=85130753451&partnerID=8YFLogxK

U2 - 10.3233/JAD-220019

DO - 10.3233/JAD-220019

M3 - Journal article

C2 - 35342093

AN - SCOPUS:85130753451

VL - 87

SP - 685

EP - 699

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 2

ER -