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dc.contributor.author서혜명-
dc.date.accessioned2019-09-24T07:43:28Z-
dc.date.available2019-09-24T07:43:28Z-
dc.date.issued2005-05-
dc.identifier.citationHUMAN MOLECULAR GENETICS, v. 14, No. 13, Page. 1709-1725en_US
dc.identifier.issn0964-6906-
dc.identifier.issn1460-2083-
dc.identifier.urihttps://academic.oup.com/hmg/article/14/13/1709/621031-
dc.identifier.urihttps://repository.hanyang.ac.kr/handle/20.500.11754/110623-
dc.description.abstractMolecular differences between dopamine (DA) neurons may explain why the mesostriatal DA neurons in the A9 region preferentially degenerate in Parkinson's disease (PD) and toxic models, whereas the adjacent A10 region mesolimbic and mesocortical DA neurons are relatively spared. To characterize innate physiological differences between A9 and A10 DA neurons, we determined gene expression profiles in these neurons in the adult mouse by laser capture microdissection, microarray analysis and real-time PCR. We found 42 genes relatively elevated in A9 DA neurons, whereas 61 genes were elevated in A10 DA neurons [>2-fold; false discovery rate (FDR) < 1%]. Genes of interest for further functional analysis were selected by criteria of (I) fold differences in gene expression, (ii) real-time PCR validation and (iii) potential roles in neurotoxic or protective biochemical pathways. Three A9-elevated molecules [G-protein coupled inwardly rectifying K channel 2 (GIRK2), adenine nucleotide translocator 2 (ANT-2) and the growth factor IGF-1] and three A10-elevated peptides (GRP, CGRP and PACAP) were further examined in both alpha-synuclein overexpressing PC12 (PC12-alpha Syn) cells and rat primary ventral mesencephalic (VM) cultures exposed to MPP+ neurotoxicity. GIRK2-positive DA neurons were more vulnerable to MPP+ toxicity and overexpression of GIRK2 increased the vulnerability of PC12-alpha Syn cells to the toxin. Blocking of ANT decreased vulnerability to MPP+ in both cell culture systems. Exposing cells to IGF-1, GRP and PACAP decreased vulnerability of both cell types to MPP+, whereas CGRP protected PC12-alpha Syn cells but not primary VM DA neurons. These results indicate that certain differentially expressed molecules in A9 and A10 DA neurons may play key roles in their relative vulnerability to toxins and PD.en_US
dc.description.sponsorshipWe thank Dr Vikram Khurana for discussions and reading of the manuscript; Chin-Yi Chu and Oliver Cooper for excellent technical assistance. We also thank Dr Peter Lansbury for providing synuclein overexpressing PC12 cells. This study was conducted in part in the facilities and collaborative network provided by the Harvard Center for Neurodegeneration and Repair and was supported by funds from the NIH/NINDS P50 Parkinson's Disease Udall Research Centers of Excellence to McLean/Harvard Medical School (PI:OI), USAMRMC grant DAMD 17-01-1-0762 (PI:OI), the Michael Stern Foundation for Parkinson's Disease Research, the Consolidated Anti-Aging Foundation and the Orchard Foundation.en_US
dc.language.isoen_USen_US
dc.publisherOXFORD UNIV PRESSen_US
dc.subjectpolymerase chain reactionen_US
dc.subjectcell culture techniquesen_US
dc.subjectgene expressionen_US
dc.subjectcalcitonin gene-related peptideen_US
dc.subjectgene expression profilingen_US
dc.subjectgenesen_US
dc.subjectinsulin-like growth factor ien_US
dc.subjectmidbrainen_US
dc.subjectneuronsen_US
dc.subjecttoxinsen_US
dc.subjectmiceen_US
dc.subjecttoxic effecten_US
dc.subjectlaser capture microdissectionen_US
dc.subjectpituitary adenylate cyclase activating polypeptideen_US
dc.subjectdopaminergic neuronsen_US
dc.subjectemotional vulnerabilityen_US
dc.subjectmoleculeen_US
dc.titleCell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protectionen_US
dc.typeArticleen_US
dc.identifier.doi10.1093/hmg/ddi178-
dc.relation.journalHUMAN MOLECULAR GENETICS-
dc.contributor.googleauthorChung, CY-
dc.contributor.googleauthorSeo, H-
dc.contributor.googleauthorSonntag, KC-
dc.contributor.googleauthorBrooks, A-
dc.contributor.googleauthorLin, L-
dc.contributor.googleauthorIsacson, O-
dc.relation.code2009203745-
dc.sector.campusE-
dc.sector.daehakCOLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E]-
dc.sector.departmentDEPARTMENT OF MOLECULAR AND LIFE SCIENCE-
dc.identifier.pidhseo-


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