Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus
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-inhib...
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| Main Authors: | , , , |
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| Format: | Book |
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Elsevier,
2017-04-01T00:00:00Z.
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| Summary: | 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. Keywords: Hypothalamus, Arcuate nucleus, Agouti-related protein, Neuropeptide Y, Electron microscopy, 3D reconstruction |
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| Item Description: | 2212-8778 10.1016/j.molmet.2017.01.004 |