Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases

PLoS One. 2013;8(3):e58473. doi: 10.1371/journal.pone.0058473. Epub 2013 Mar 4.


Monoaminergic and neuropeptidergic neurons regulate a wide variety of behaviors, such as feeding, sleep/wakefulness behavior, stress response, addiction, and social behavior. These neurons form neural circuits to integrate different modalities of behavioral and environmental factors, such as stress, maternal care, and feeding conditions. One possible mechanism for integrating environmental factors through the monoaminergic and neuropeptidergic neurons is through the epigenetic regulation of gene expression via altered acetylation of histones. Histone deacetylases (HDACs) play an important role in altering behavior in response to environmental factors. Despite increasing attention and the versatile roles of HDACs in a variety of brain functions and disorders, no reports have detailed the localization of the HDACs in the monoaminergic and neuropeptidergic neurons. Here, we examined the expression profile of the HDAC protein family from HDAC1 to HDAC11 in corticotropin-releasing hormone, oxytocin, vasopressin, agouti-related peptide (AgRP), pro-opiomelanocortin (POMC), orexin, histamine, dopamine, serotonin, and noradrenaline neurons. Immunoreactivities for HDAC1,-2,-3,-5,-6,-7,-9, and -11 were very similar among the monoaminergic and neuropeptidergic neurons, while the HDAC4, -8, and -10 immunoreactivities were clearly different among neuronal groups. HDAC10 expression was found in AgRP neurons, POMC neurons, dopamine neurons and noradrenaline neurons but not in other neuronal groups. HDAC8 immunoreactivity was detected in the cytoplasm of almost all histamine neurons with a pericellular pattern but not in other neuropeptidergic and monoaminergic neurons. Thus, the differential expression of HDACs in monoaminergic and neuropeptidergic neurons may be crucial for the maintenance of biological characteristics and may be altered in response to environmental factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biogenic Monoamines / metabolism*
  • Biogenic Monoamines / pharmacology
  • Biological Transport
  • Brain / cytology
  • Brain / metabolism*
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cytoplasm / metabolism
  • Cytoplasm / ultrastructure
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Gene Expression*
  • Histone Deacetylases / classification
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Microtomy
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Neuropeptides / metabolism*
  • Neuropeptides / pharmacology


  • Biogenic Monoamines
  • Neuropeptides
  • Histone Deacetylases

Grant support

This work was supported by JSPS KAKENHI Grant Number 22590228 to HF, MEXT KAKENHI Grant Number 23126526 to HF, the Research Grant from TANITA Healthy Weight Community Trust to HF, the Research Promotion Grant from Toho University Graduate School of Medicine (No.12-02) to HF, and the Research Grant from Toho University School of Medicine (No.21-3) to HF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.