Striatal alterations of secretogranin-1, somatostatin, prodynorphin, and cholecystokinin peptides in an experimental mouse model of Parkinson disease.
The principal causative pathology of Parkinson disease is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta projecting to the striatum in the brain. The information regarding the expression of neuropeptides in parkinsonism is very limited. Here we have elucidated striatal neuropeptide mechanisms in experimental parkinsonism using the unilateral 6-hydroxydopamine model to degenerate dopamine neurons. A thoroughly controlled sample preparation technique together with a peptidomics approach and targeted neuropeptide sequence collections enabled sensitive detection, identification, and relative quantitation of a great number of endogenous neuropeptides. Previously not recognized alterations in neuropeptide levels were identified in the unilateral lesioned mice with or without subchronic 3,4-dihydroxy-L-phenylalanine administration, the conventional treatment of Parkinson disease. Several of these peptides originated from the same precursor such as secretogranin-1, somatostatin, prodynorphin, and cholecystokinin. Disease-related biotransformation of precursors into individual peptides was observed in the experimental model of Parkinson disease. Several previously unreported potentially biologically active peptides were also identified from the striatal samples. This study provides further evidence that neuropeptides take part in mediating the central nervous system failure associated with Parkinson disease.
Nilsson
Anna
A
Department of Pharmaceutical Biosciences, Medical Mass Spectrometry, Uppsala University, SE-75123 Uppsala, Sweden.
Fälth
Maria
M
Zhang
Xiaoqun
X
Kultima
Kim
K
Sköld
Karl
K
Svenningsson
Per
P
Andrén
Per E
PE
D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000737:chemistry / Q000378:metabolism; D053378:Chromogranin B / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D004745:Enkephalins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011180:Postmortem Changes; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D013004:Somatostatin / Q000737:chemistry / Q000378:metabolism; D014020:Tissue Extracts; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D053378:Chromogranin B; D004745:Enkephalins; D010455:Peptides; D011498:Protein Precursors; D014020:Tissue Extracts; C506137:chromogranin B, mouse; D013004:Somatostatin; D016627:Oxidopamine; D002766:Cholecystokinin; C033660:preproenkephalin; D014446:Tyrosine 3-Monooxygenase