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

Neurosci Bull. 2019 Apr;35(2):205-215. doi: 10.1007/s12264-019-00339-y. Epub 2019 Jan 31.

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: Bipolar disorder; ErbB4; Locus coeruleus; Major depressive disorder; Tyrosine hydroxylase.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bipolar Disorder / metabolism*
  • Bipolar Disorder / pathology
  • Depressive Disorder, Major / metabolism*
  • Depressive Disorder, Major / pathology
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry / methods
  • Locus Coeruleus / metabolism*
  • Locus Coeruleus / pathology
  • Male
  • Melanins / metabolism*
  • Microscopy / methods
  • Middle Aged
  • Neurons / metabolism
  • Neurons / pathology
  • Receptor, ErbB-4 / metabolism*
  • Sensitivity and Specificity
  • Spectrum Analysis / methods
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Melanins
  • neuromelanin
  • Tyrosine 3-Monooxygenase
  • ERBB4 protein, human
  • Receptor, ErbB-4