Changes in the neuronal activity in the pedunculopontine nucleus in chronic MPTP-treated primates: an in situ hybridization study of cytochrome oxidase subunit I, choline acetyl transferase and substance P mRNA expression.
The pedunculopontine nucleus is a mesencephalic nucleus that has widespread and reciprocal connections with the basal ganglia. It has been implicated in the physiopathology of akinesia, rigidity, gait failure and sleep disorders associated with Parkinson's disease. In this study, in situ hybridization was used to examine the changes in neuronal metabolic activity (measuring cytochrome oxidase subunit I) and in the level of acetylcholine and Substance P synthesis in the pedunculopontine nucleus of monkeys chronically treated with MPTP. Significant reductions were observed in cytochrome oxidase subunit I (p = 0.001), choline acetyl transferase (p = 0.003) and substance P (p = 0.006) mRNA expression in parkinsonian animals compared with controls, indicating that pedunculopontine cholinergic neurons activity decreases with parkinsonism.
Gomez-Gallego
M
M
Department of Neurology, Virgen de la Arrixaca University Hospital, Murcia, Spain. mgomezg@um.es
Fernandez-Villalba
E
E
Fernandez-Barreiro
A
A
Herrero
M T
MT
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000235:genetics*; D005260:Female; D017403:In Situ Hybridization; D008252:Macaca fascicularis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism*; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000235:genetics*
D015415:Biomarkers; D009498:Neurotoxins; D021122:Protein Subunits; D012333:RNA, Messenger; D013373:Substance P; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003576:Electron Transport Complex IV; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine