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Quantification of Tyrosine Hydroxylase and ErbB4 in the Locus Coeruleus of Mood Disorder Patients Using a Multispectral Method to Prevent Interference with Immunocytochemical Signals by Neuromelanin

  • Lei Guo
  • Jochem Stormmesand
  • Zheng Fang
  • Qingbin Zhu
  • Rawien Balesar
  • Joop van Heerikhuize
  • Arja Sluiter
  • Dick Swaab
  • Ai-Min BaoEmail author
METHOD
  • 49 Downloads

Abstract

The locus coeruleus (LC) has been studied in major depressive disorder (MDD) and bipolar disorder (BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin. We found significantly increased tyrosine hydroxylase (TH) in the LC of MDD patients—thus validating the method—but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.

Keywords

Major depressive disorder Bipolar disorder Tyrosine hydroxylase ErbB4 Locus coeruleus 

Notes

Acknowledgements

This work was supported by the National Key R&D Program of China (2016YFC1306700) and the National Natural Science Foundation of China (91332102 and 31271130). We thank Mr. Bart Fisser, Hugo McGurran, Ling Shan, and Michiel Kooreman for technical support, Prof. Xiao-Ming Li for insightful comments, and Wilma Verweij for secretarial assistance.

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Lei Guo
    • 1
    • 2
  • Jochem Stormmesand
    • 2
  • Zheng Fang
    • 1
  • Qingbin Zhu
    • 1
    • 3
  • Rawien Balesar
    • 2
  • Joop van Heerikhuize
    • 2
  • Arja Sluiter
    • 2
  • Dick Swaab
    • 2
  • Ai-Min Bao
    • 1
    Email author
  1. 1.Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of MedicineHangzhouChina
  2. 2.Netherlands Institute for NeuroscienceInstitute of the Royal Netherlands Academy of Arts and SciencesAmsterdamthe Netherlands
  3. 3.Department of Neurology, Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina

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