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Melanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate-putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.
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http://dx.doi.org/10.1002/jnr.24651 | DOI Listing |
Biochem Biophys Res Commun
May 2025
Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8521, Japan. Electronic address:
Long-term stress contributes to depressive disorders, for which monoamine-based treatments are often inadequate. This study identifies neuronal primary cilia as critical regulators of stress-induced depressive-like behavior. In mice, short-term restraint stress (3 days) reduced cilia length and the proportion of cilia-bearing neurons within the frontal association cortex (FrA).
View Article and Find Full Text PDFJ Biochem
November 2024
Primary cilia are thin hair-like organelles that protrude from the surface of most mammalian cells. They act as specialized cell antennas that can vary widely in response to specific stimuli. However, the effect of changes in cilia length on cellular signaling and behavior remains unclear.
View Article and Find Full Text PDFMethods Cell Biol
March 2023
Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan. Electronic address:
The primary cilium is a structural organelle present in most mammalian cells. Primary cilia are enriched with a unique protein repertoire distinct from that of the cytosol and the plasma membrane. Such a highly organized microenvironment creates effective machinery for translating extracellular cues into intracellular signals.
View Article and Find Full Text PDFeNeuro
March 2023
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202
Primary cilia are cellular appendages critical for diverse types of Signaling. They are found on most cell types, including cells throughout the CNS. Cilia preferentially localize certain G-protein-coupled receptors (GPCRs) and are critical for mediating the signaling of these receptors.
View Article and Find Full Text PDFMol Neurobiol
January 2022
Departments of Pharmaceutical Sciences, School of Pharmacy, University of California, Irvine, CA, 92697, USA.
The melanin-concentrating hormone (MCH) system is involved in numerous functions, including energy homeostasis, food intake, sleep, stress, mood, aggression, reward, maternal behavior, social behavior, and cognition. In rodents, MCH acts on MCHR1, a G protein-coupled receptor, which is widely expressed in the brain and abundantly localized to neuronal primary cilia. Cilia act as cells' antennas and play crucial roles in cell signaling to detect and transduce external stimuli to regulate cell differentiation and migration.
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