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Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus.
Mol Metab. 2017 04; 6(4):374-381.MM

Abstract

OBJECTIVES

Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood. Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations.

METHODS

We applied immunohistochemical labeling of CB1R for light microscopy and electron microscopy combined with three-dimensional reconstruction from serial sections in CB1R-expressing and CB1R-null mice, which served as a negative control. Hunger-promoting neurons expressing Agouti-related protein and neuropeptide Y (AgRP/NPY) in the hypothalamic arcuate nucleus were identified in NPY-GFP and NPY-hrGFP mice.

RESULTS

Using three-dimensional reconstruction from serial sections we demonstrated numerous discontinuous segments of anti-CB1R labeling in the synaptic boutons and axonal shafts in the arcuate nucleus. We observed CB1R in the symmetric, presumed GABAergic, synaptic boutons innervating AgRP/NPY neurons. We also detected CB1R-containing axons producing symmetric and asymmetric synapses onto AgRP/NPY-negative neurons. Furthermore, we identified CB1R in close apposition to the endocannabinoid (2-arachidonoylglycerol)-synthesizing enzyme diacylglycerol lipase-alpha at AgRP/NPY neurons.

CONCLUSIONS

Our immunohistochemical and ultrastructural study demonstrates the morphological substrate for cannabinoid-conducted feeding behavior via retrograde dis-inhibition of hunger-promoting AgRP/NPY neurons.

Links

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Authors+Show Affiliations

Morozov YM
Department of Neuroscience, Yale University School of Medicine, 06520 New Haven, CT, USA; Kavli Institute for Neuroscience, Yale University School of Medicine, 06520 New Haven, CT, USA. Electronic address: yury.morozov@yale.edu.
Koch M
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, 06520 New Haven, CT, USA; Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany.
Rakic P
Department of Neuroscience, Yale University School of Medicine, 06520 New Haven, CT, USA; Kavli Institute for Neuroscience, Yale University School of Medicine, 06520 New Haven, CT, USA.
Horvath TL
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, 06520 New Haven, CT, USA. Electronic address: tamas.horvath@yale.edu.

MeSH

Agouti-Related ProteinAnimalsArcuate Nucleus of HypothalamusAxonsMiceMice, Inbred C57BLNeuropeptide YReceptor, Cannabinoid, CB1

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28377876

Citation

Morozov, Yury M., et al. "Cannabinoid Type 1 Receptor-containing Axons Innervate NPY/AgRP Neurons in the Mouse Arcuate Nucleus." Molecular Metabolism, vol. 6, no. 4, 2017, pp. 374-381.
Morozov YM, Koch M, Rakic P, et al. Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus. Mol Metab. 2017;6(4):374-381.
Morozov, Y. M., Koch, M., Rakic, P., & Horvath, T. L. (2017). Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus. Molecular Metabolism, 6(4), 374-381. https://doi.org/10.1016/j.molmet.2017.01.004
Morozov YM, et al. Cannabinoid Type 1 Receptor-containing Axons Innervate NPY/AgRP Neurons in the Mouse Arcuate Nucleus. Mol Metab. 2017;6(4):374-381. PubMed PMID: 28377876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus. AU - Morozov,Yury M, AU - Koch,Marco, AU - Rakic,Pasko, AU - Horvath,Tamas L, Y1 - 2017/01/27/ PY - 2016/12/06/received PY - 2017/01/04/revised PY - 2017/01/09/accepted PY - 2017/4/6/entrez PY - 2017/4/6/pubmed PY - 2018/11/16/medline KW - 3D reconstruction KW - Agouti-related protein KW - Arcuate nucleus KW - Electron microscopy KW - Hypothalamus KW - Neuropeptide Y SP - 374 EP - 381 JF - Molecular metabolism JO - Mol Metab VL - 6 IS - 4 N2 - OBJECTIVES: Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood. Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations. METHODS: We applied immunohistochemical labeling of CB1R for light microscopy and electron microscopy combined with three-dimensional reconstruction from serial sections in CB1R-expressing and CB1R-null mice, which served as a negative control. Hunger-promoting neurons expressing Agouti-related protein and neuropeptide Y (AgRP/NPY) in the hypothalamic arcuate nucleus were identified in NPY-GFP and NPY-hrGFP mice. RESULTS: Using three-dimensional reconstruction from serial sections we demonstrated numerous discontinuous segments of anti-CB1R labeling in the synaptic boutons and axonal shafts in the arcuate nucleus. We observed CB1R in the symmetric, presumed GABAergic, synaptic boutons innervating AgRP/NPY neurons. We also detected CB1R-containing axons producing symmetric and asymmetric synapses onto AgRP/NPY-negative neurons. Furthermore, we identified CB1R in close apposition to the endocannabinoid (2-arachidonoylglycerol)-synthesizing enzyme diacylglycerol lipase-alpha at AgRP/NPY neurons. CONCLUSIONS: Our immunohistochemical and ultrastructural study demonstrates the morphological substrate for cannabinoid-conducted feeding behavior via retrograde dis-inhibition of hunger-promoting AgRP/NPY neurons. SN - 2212-8778 UR - https://www.unboundmedicine.com/medline/citation/28377876/Cannabinoid_type_1_receptor_containing_axons_innervate_NPY/AgRP_neurons_in_the_mouse_arcuate_nucleus_ DB - PRIME DP - Unbound Medicine ER -