Minimal Age-Related Alterations in Behavioral and Hematological Parameters in Trace Amine-Associated Receptor 1 (TAAR1) Knockout Mice

Abstract

Since the discovery in 2001, the G protein-coupled trace amine-associated receptor 1 (TAAR1) has become an important focus of research targeted on evaluation of its role in the central nervous system (CNS). Meanwhile, impact of TAAR1 in the peripheral organs is less investigated. Expression of TAAR1 was demonstrated in different peripheral tissues: pancreatic β-cells, stomach, intestines, white blood cells (WBC), and thyroid. However, the role of TAAR1 in regulation of hematological parameters has not been investigated yet. In this study, we performed analysis of anxiety-related behaviors, a complete blood count (CBC), erythrocyte fragility, as well as FT3/FT4 thyroid hormones levels in adult and middle-aged TAAR1 knockout mice. Complete blood count analysis was performed on a Siemens Advia 2120i hematology analyzer and included more than 35 measured and calculated parameters. Erythrocyte fragility test evaluated spherocytosis pathologies of red blood cells (RBC). No significant alterations in essentially all these parameters were found in mice without TAAR1. However, comparative aging analysis has revealed a decreased neutrophils level in the middle-aged TAAR1 knockout mouse group. Minimal alterations in these parameters observed in TAAR1 knockout mice suggest that future TAAR1-based therapies should exert little hematological effect and thus will likely have a good safety profile.

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Acknowledgements

This study was supported by the Russian Science Foundation Grant No. 19-75-30008. We are grateful to Lundbeck A/G and Lundbeck USA for generously providing TAAR1 knockout mice.

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ZIS, TIY, KLG, and KIV performed the experiments (CBC, EFT, EPM), wrote the manuscript, acquired the data, and created the figures. SEL and KAA performed the experiments (thyroid parameters) and participated in writing the manuscript. DSG, KVA, VOL, and GRR designed the study and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

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Correspondence to I. S. Zhukov.

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The authors declare that they have no conflict of interest.

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The experiments were carried out in full compliance with ethical standards approved by the FELASA and RusLASA organizations of welfare of laboratory animal use and were approved by the Saint Petersburg State University Ethical Committee for Animal Research.

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Zhukov, I.S., Kubarskaya, L.G., Tissen, I.Y. et al. Minimal Age-Related Alterations in Behavioral and Hematological Parameters in Trace Amine-Associated Receptor 1 (TAAR1) Knockout Mice. Cell Mol Neurobiol 40, 273–282 (2020). https://doi.org/10.1007/s10571-019-00721-4

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Keywords

  • Trace amines
  • Anxiety
  • Aging
  • Hematology
  • Thyroid
  • TAAR1
  • Leukocytes
  • Neutrophils