title: Mapping of endogenous morphine-like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells.
abstract: Endogenous morphine, morphine-6-glucuronide, and codeine, which are structurally identical to vegetal alkaloids, can be synthesized by mammalian cells from dopamine. However, the role of brain endogenous morphine and its derivative compounds is a matter of debate, and knowledge about its distribution is lacking. In this study, by using a validated antibody, we describe a precise mapping of endogenous morphine-like compounds (morphine and/or its glucuronides and/or codeine) in the mouse brain. First, a mass spectrometry approach confirmed the presence of morphine and codeine in mouse brain, but also, of morphine-6-glucuronide and morphine-3-glucuronide representing two metabolites of morphine. Second, light microscopy allowed us to observe immunopositive cell somas and cytoplasmic processes throughout the mouse brain. Morphine-like immunoreactivity was present in various structures including the hippocampus, olfactory bulb, band of Broca, basal ganglia, and cerebellum. Third, by using confocal microscopy and immunofluroscence co-localization, we characterized cell types containing endogenous opiates. Interestingly, we observed that morphine-like immunoreactivity throughout the encephalon is mainly present in γ-aminobutyric acid (GABA)ergic neurons. Astrocytes were also labeled throughout the entire brain, in the cell body, in the cytoplasmic processes, and in astrocytic feet surrounding blood vessels. Finally, ultrastructural localization of morphine-like immunoreactivity was determined by electron microscopy and showed the presence of morphine-like label in presynaptic terminals in the cerebellum and postsynaptic terminals in the rest of the mouse brain. In conclusion, the presence of endogenous morphine-like compounds in brain regions not usually involved in pain modulation opens the exciting opportunity to extend the role and function of endogenous alkaloids far beyond their analgesic functions.
authors: Nociception and Pain Department, Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, F-67084 Strasbourg, France.
authors: Alexis
authors: A
authors: Laux
authors: Arnaud H
authors: AH
authors: Muller
authors: Monique
authors: M
authors: Miehe
authors: Sylvie
authors: S
authors: Dirrig-Grosch
authors: Jean Christophe
authors: JC
authors: Deloulme
authors: François
authors: F
authors: Delalande
authors: Denise
authors: D
authors: Stuber
authors: Dominique
authors: D
authors: Sage
authors: Alain
authors: A
authors: Van Dorsselaer
authors: Pierrick
authors: P
authors: Poisbeau
authors: Dominique
authors: D
authors: Aunis
authors: Yannick
authors: Y
authors: Goumon
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000737:chemistry* / Q000648:ultrastructure; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism; D001923:Brain Chemistry; D003061:Codeine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000737:chemistry*; D009022:Morphine Derivatives / Q000378:metabolism; D009474:Neurons / Q000737:chemistry* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D009022:Morphine Derivatives; D005680:gamma-Aminobutyric Acid; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide; D003061:Codeine; D004298:Dopamine