Volume 35, Issue. 2, April, 2019

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 1,2 • Jochem Stormmesand2 • Zheng Fang1 • Qingbin Zhu 1,3 •Rawien Balesar2 • Joop van Heerikhuize2 • Arja Sluiter2 • Dick Swaab2 •Ai-Min Bao 1

1 Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China
2 Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, the Netherlands
3 Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China


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.



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