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Vortioxetine administration attenuates cognitive and synaptic deficits in 5×FAD mice

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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.

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Acknowledgments

We thank the National Center for Protein Sciences at Peking University in Beijing, China, for assisting us with the image acquisition and Li-Qin Fu for helping us with the image optimization.

Funding

This work was supported in part by the National Key R&D Program of China (No.2018YFC1314200), Beijing Municipal Science &Technology Commission (No. Z161100002616021), and National Key Research and Development Program of China (No. 2017YFC1311100).

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Author notes

  1. Li-Xin Jiang and Geng-Di Huang contributed equally to this work.

Authors and Affiliations

  1. School of Mental Health, Wenzhou Medical University, Chashan Higher Education Park, Ouhai District, Wenzhou, 325035, China

    Li-Xin Jiang & Xin Yu

  2. Peking University Institute of Mental Health (Sixth Hospital), No. 51 Huayuanbei Road, Haidian District, Beijing, 100191, China

    Li-Xin Jiang, Geng-Di Huang, Huali Wang & Xin Yu

  3. National Clinical Research Center for Mental Disorders & NHC Key Laboratory of Mental Health, Peking University, Beijing, 100191, China

    Li-Xin Jiang, Geng-Di Huang, Huali Wang & Xin Yu

  4. Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, 100191, China

    Li-Xin Jiang, Geng-Di Huang, Huali Wang, Chen Zhang & Xin Yu

  5. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China

    Feng Su

  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

    Feng Su & Chen Zhang

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  1. Li-Xin Jiang
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Contributions

L.X.J., G.D.H., H.W., and X.Y. designed the experiments. L.X.J. and G.D.H. performed the experiments. L.X.J. and S.F. analyzed and interpreted the data. H.W., C.Z., and X.Y. commented on the manuscript. L.X.J. and X.Y. wrote the manuscript.

Corresponding authors

Correspondence to Huali Wang, Chen Zhang or Xin Yu.

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Jiang, LX., Huang, GD., Su, F. et al. Vortioxetine administration attenuates cognitive and synaptic deficits in 5×FAD mice. Psychopharmacology 237, 1233–1243 (2020). https://doi.org/10.1007/s00213-020-05452-9

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