title: Endogenous morphine-like compound immunoreactivity increases in parkinsonism.
abstract: Morphine is endogenously synthesized in the central nervous system and endogenous dopamine is thought to be necessary for endogenous morphine formation. As Parkinson's disease results from the loss of dopamine and is associated with central pain, we considered how endogenous morphine is regulated in the untreated and l-DOPA-treated parkinsonian brain. However, as the cellular origin and overall distribution of endogenous morphine remains obscure in the pathological adult brain, we first characterized the distribution of endogenous morphine-like compound immunoreactive cells in the rat striatum. We then studied changes in the endogenous morphine-like compound immunoreactivity of medium spiny neurons in normal, Parkinson's disease-like and l-DOPA-treated Parkinson's disease-like conditions in experimental (rat and monkey) and human Parkinson's disease. Our results reveal an unexpected dramatic upregulation of neuronal endogenous morphine-like compound immunoreactivity and levels in experimental and human Parkinson's disease, only partially normalized by l-DOPA treatment. Our data suggest that endogenous morphine formation is more complex than originally proposed and that the parkinsonian brain experiences a dramatic upregulation of endogenous morphine immunoreactivity. The functional consequences of such endogenous morphine upregulation are as yet unknown, but based upon the current knowledge of morphine signalling, we hypothesize that it is involved in fatigue, depression and pain symptoms experienced by patients with Parkinson's disease.
authors: University of Bordeaux, Institut des Maladies Neurodegeneratives, Bordeaux, France.
authors: Giselle
authors: G
authors: Charron
authors: Evelyne
authors: E
authors: Doudnikoff
authors: Alexis
authors: A
authors: Laux
authors: Amandine
authors: A
authors: Berthet
authors: Gregory
authors: G
authors: Porras
authors: Marie-Hélène
authors: MH
authors: Canron
authors: Pedro
authors: P
authors: Barroso-Chinea
authors: Qin
authors: Q
authors: Li
authors: Chuan
authors: C
authors: Qin
authors: Marika
authors: M
authors: Nosten-Bertrand
authors: Bruno
authors: B
authors: Giros
authors: François
authors: F
authors: Delalande
authors: Alain
authors: A
authors: Van Dorsselaer
authors: Anne
authors: A
authors: Vital
authors: Yannick
authors: Y
authors: Goumon
authors: Erwan
authors: E
authors: Bezard
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000172:deficiency / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron / Q000379:methods; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism; D009930:Organic Chemicals / Q000378:metabolism; D016627:Oxidopamine / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D009930:Organic Chemicals; D017448:Receptors, Dopamine D2; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C016005:morphine-like compounds (non-peptide); D007980:Levodopa; D019805:alpha-Methyltyrosine; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D004298:Dopamine