Abstract

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.

Highlights

  • Monoaminergic and neuropeptidergic neurons regulate a wide variety of behaviors, such as feeding, sleep/wakefulness behavior, stress response, addiction, and social behavior

  • Nuclear HDAC1 immunoreactivity was found in almost all nuclei of the corticotropin-releasing hormone (CRH) neurons (9266%), oxytocin neurons (9561%), and vasopressin neurons (10060%) of the paraventricular nucleus (PVN); the orexin neurons (10060%) of the lateral hypothalamic area (LHA); the agouti-related peptide (AgRP) neurons (10060%) and POMC neurons (10060%) of the arcuate nucleus (ARC); the histamine neurons (9166%) of the tuberomammillary nucleus (TMN); the dopamine neurons (10060%) of the ventral tegmental area (VTA); the serotonin neurons (10060%) of the dorsal raphe (DR); and the noradrenaline neurons (10060%) of the locus coeruleus (LC) (Figures 1A–I, Table 2)

  • HDAC1-immunoreactive puncta were uniform in size and widely distributed in the PVN, LHA, ARC, TMN, DR and LC

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Summary

Introduction

Monoaminergic and neuropeptidergic neurons regulate a wide variety of behaviors, such as feeding, sleep/wakefulness behavior, stress response, addiction, and social behavior. Feeding behavior is mainly regulated by orexigenic neurons containing neuropeptide Y (NPY) and agouti-related peptide (AgRP) and by anorexigenic neurons containing pro-opiomelanocortin (POMC). Both of these types of neurons are localized in the hypothalamic arcuate nucleus (ARC) [1]. Orexin ( known as hypocretin), which was originally identified as an orexigenic neuropeptide, is expressed in the lateral hypothalamic area (LHA) and plays a crucial role in sleep/wakefulness behavior, reward behavior, addiction, and body weight regulation [2,3,4]. The PVN contains neurons that produce oxytocin and vasopressin, which are important for social behavior [7]

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