Li-Xin Jiang1,2,3,4, Geng-Di Huang2,3,4, Feng Su5,6, Huali Wang7,8,9, Chen Zhang10,11, Xin Yu12,13,14,15. 1. School of Mental Health, Wenzhou Medical University, Chashan Higher Education Park, Ouhai District, Wenzhou, 325035, China. 2. Peking University Institute of Mental Health (Sixth Hospital), No. 51 Huayuanbei Road, Haidian District, Beijing, 100191, China. 3. National Clinical Research Center for Mental Disorders & NHC Key Laboratory of Mental Health, Peking University, Beijing, 100191, China. 4. Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, 100191, China. 5. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. 6. School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, No.10 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, China. 7. Peking University Institute of Mental Health (Sixth Hospital), No. 51 Huayuanbei Road, Haidian District, Beijing, 100191, China. huali_wang@bjmu.edu.cn. 8. National Clinical Research Center for Mental Disorders & NHC Key Laboratory of Mental Health, Peking University, Beijing, 100191, China. huali_wang@bjmu.edu.cn. 9. Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, 100191, China. huali_wang@bjmu.edu.cn. 10. Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, 100191, China. czhang@ccmu.edu.cn. 11. School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, No.10 Xitoutiao, You'anmenwai, Fengtai District, Beijing, 100069, China. czhang@ccmu.edu.cn. 12. School of Mental Health, Wenzhou Medical University, Chashan Higher Education Park, Ouhai District, Wenzhou, 325035, China. yuxin@bjmu.edu.cn. 13. Peking University Institute of Mental Health (Sixth Hospital), No. 51 Huayuanbei Road, Haidian District, Beijing, 100191, China. yuxin@bjmu.edu.cn. 14. National Clinical Research Center for Mental Disorders & NHC Key Laboratory of Mental Health, Peking University, Beijing, 100191, China. yuxin@bjmu.edu.cn. 15. Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, 100191, China. yuxin@bjmu.edu.cn.
Abstract
RATIONALE AND OBJECTIVE: Vortioxetine has been reported to exhibit a variety of neurobiological functions and neuroprotective effects. In the present study, we aimed to investigate the effects of vortioxetine on cognitive performance in a transgenic mouse model of Alzheimer's disease (AD). METHODS: We administered vortioxetine (10 mg/kg, i.p., every day, for approximately 6 weeks), which acts on multiple 5-serotonin (5-HT) receptors, to 3.5-month-old 5×FAD mice. Subsequently, we used the open field (OF) test to detect anxiety-like behavior in the mice. The novel object recognition (NOR) test and Morris water maze (MWM) were used to assess the cognitive states of the 5×FAD mice. We also measured the levels of insoluble amyloid plaques and soluble β-amyloid (Aβ) plaques. Finally, we explored the expression levels of postsynaptic density protein 95 (PSD95), synaptophysin (SYP), and synaptotagmin-1 (SYT1) in the hippocampus of the mice. RESULTS: The administration of vortioxetine effectively reversed the reduction in anxiety-type behaviors in 5×FAD mice and improved the impairment in recognition memory and spatial reference memory. However, we did not find that vortioxetine decreased or delayed the formation of amyloid plaques or Aβ. Interestingly, we found a significant increase in the expression levels of PSD95, SYP, and SYT1 in the 5×FAD mice after vortioxetine treatment compared with the control group. CONCLUSION: These results demonstrate that vortioxetine may improve cognitive impairment in 5×FAD mice. The role in cognitive improvement may be related to the beneficial effects of vortioxetine on synaptic function.
RATIONALE AND OBJECTIVE: Vortioxetine has been reported to exhibit a variety of neurobiological functions and neuroprotective effects. In the present study, we aimed to investigate the effects of vortioxetine on cognitive performance in a transgenic mouse model of Alzheimer's disease (AD). METHODS: We administered vortioxetine (10 mg/kg, i.p., every day, for approximately 6 weeks), which acts on multiple 5-serotonin (5-HT) receptors, to 3.5-month-old 5×FAD mice. Subsequently, we used the open field (OF) test to detect anxiety-like behavior in the mice. The novel object recognition (NOR) test and Morris water maze (MWM) were used to assess the cognitive states of the 5×FAD mice. We also measured the levels of insoluble amyloid plaques and soluble β-amyloid (Aβ) plaques. Finally, we explored the expression levels of postsynaptic density protein 95 (PSD95), synaptophysin (SYP), and synaptotagmin-1 (SYT1) in the hippocampus of the mice. RESULTS: The administration of vortioxetine effectively reversed the reduction in anxiety-type behaviors in 5×FAD mice and improved the impairment in recognition memory and spatial reference memory. However, we did not find that vortioxetine decreased or delayed the formation of amyloid plaques or Aβ. Interestingly, we found a significant increase in the expression levels of PSD95, SYP, and SYT1 in the 5×FAD mice after vortioxetine treatment compared with the control group. CONCLUSION: These results demonstrate that vortioxetine may improve cognitive impairment in 5×FAD mice. The role in cognitive improvement may be related to the beneficial effects of vortioxetine on synaptic function.
Entities:
Keywords:
5×FAD; Alzheimer’s disease; Amyloid; Morris water maze; Novel object recognition test; Open field test; Synaptic marker; Vortioxetine
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