Antidepressant sertraline increases thioflavin-S and Congo red deposition in APPswe/PSEN1dE9 transgenic mice

Ming-Hsuan Liao; Yen-Kuang Lin; Fong-Ying Gau; Chun-Che Tseng; Da-Chih Wu; Chu-Yuan Hsu; Kuo-Hsuan Chung; Rung-Chi Li; Chaur-Jong Hu; Chee Kin Then; Shing-Chuan Shen

doi:10.3389/fphar.2023.1260838

Antidepressant sertraline increases thioflavin-S and Congo red deposition in APPswe/PSEN1dE9 transgenic mice

Front Pharmacol. 2024 Jan 8:14:1260838. doi: 10.3389/fphar.2023.1260838. eCollection 2023.

Authors

Ming-Hsuan Liao¹, Yen-Kuang Lin², Fong-Ying Gau³, Chun-Che Tseng¹, Da-Chih Wu¹, Chu-Yuan Hsu⁴, Kuo-Hsuan Chung^{5

6}, Rung-Chi Li⁷, Chaur-Jong Hu^{8

9}, Chee Kin Then^#^{10

11}, Shing-Chuan Shen^#^{1

12

13}

Affiliations

¹ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Graduate Institute of Athletics and Coaching Science, National Taiwan Sport University, Taoyuan, Taiwan.
³ School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
⁴ School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
⁶ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Division of Allergy and Immunology, University of Virginia, Charlottesville, VA, United States.
⁸ Department of Neurology, Shuang Ho Hospital, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁹ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹⁰ MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.
¹¹ Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
¹² International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹³ Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

^# Contributed equally.

Abstract

Introduction: Depression is strongly associated with Alzheimer's disease (AD). Antidepressants are commonly used in patients before and after their diagnosis of AD. To date, the relationship between antidepressants and AD remains unclear. Methods: In our study, we administered sertraline or paroxetine to wild type (WT) and APPswe/PSEN1dE9 (APP/PSEN1) transgenic mouse models for up to 12 months. We quantified the drug concentrations using LC-MS/MS analysis and measured serum serotonin level using an ELISA assay. Additionally, we evaluated the amyloid burdens through thioflavin-S and Congo red stainings, and recognition memory using the novel object recognition test. Results: Our findings revealed that mice treated with paroxetine exhibited a significantly higher level of weight gain compared to the control group and increased mortality in APP/PSEN1 mice. After 12 months of antidepressant treatment, the sertraline level was measured at 289.8 ng/g for cerebellum, while the paroxetine level was 792.9 ng/g for cerebellum. Sertraline significantly increased thioflavin-S and Congo red depositions, along with gliosis, in both isocortex and hippocampus of APP/PSEN1 mice compared to the control group. Both antidepressants also led to a decreased recognition index in APP/PSEN1 mice. Conclusion: These findings suggest a potential role of sertraline in AD pathogenesis, emphasizing the need to reassess the use of these antidepressants in patients with AD.

Keywords: APP/PSEN1; Alzheimer’s disease; SSRI; paroxetine; sertraline; β-amyloid.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Ministry of Science and Technology (MOST), Taiwan [grant numbers MOST105-2314-B-038-013-MY3(1-3), MOST103-2320-B-038-024, MOST104-2923-B-038-001- MY3(3–3)]; the National Science Council (NSC), Taiwan (grant number NSC 102-2314-B-038-042); and Taipei Medical University (TMU) (grant number TMU104-F-004).