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
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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.
KeywordsMajor depressive disorder Bipolar disorder Tyrosine hydroxylase ErbB4 Locus coeruleus
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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