Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 서혜명 | - |
dc.date.accessioned | 2019-09-24T07:43:28Z | - |
dc.date.available | 2019-09-24T07:43:28Z | - |
dc.date.issued | 2005-05 | - |
dc.identifier.citation | HUMAN MOLECULAR GENETICS, v. 14, No. 13, Page. 1709-1725 | en_US |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.issn | 1460-2083 | - |
dc.identifier.uri | https://academic.oup.com/hmg/article/14/13/1709/621031 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/110623 | - |
dc.description.abstract | Molecular 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.sponsorship | We 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.iso | en_US | en_US |
dc.publisher | OXFORD UNIV PRESS | en_US |
dc.subject | polymerase chain reaction | en_US |
dc.subject | cell culture techniques | en_US |
dc.subject | gene expression | en_US |
dc.subject | calcitonin gene-related peptide | en_US |
dc.subject | gene expression profiling | en_US |
dc.subject | genes | en_US |
dc.subject | insulin-like growth factor i | en_US |
dc.subject | midbrain | en_US |
dc.subject | neurons | en_US |
dc.subject | toxins | en_US |
dc.subject | mice | en_US |
dc.subject | toxic effect | en_US |
dc.subject | laser capture microdissection | en_US |
dc.subject | pituitary adenylate cyclase activating polypeptide | en_US |
dc.subject | dopaminergic neurons | en_US |
dc.subject | emotional vulnerability | en_US |
dc.subject | molecule | en_US |
dc.title | Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1093/hmg/ddi178 | - |
dc.relation.journal | HUMAN MOLECULAR GENETICS | - |
dc.contributor.googleauthor | Chung, CY | - |
dc.contributor.googleauthor | Seo, H | - |
dc.contributor.googleauthor | Sonntag, KC | - |
dc.contributor.googleauthor | Brooks, A | - |
dc.contributor.googleauthor | Lin, L | - |
dc.contributor.googleauthor | Isacson, O | - |
dc.relation.code | 2009203745 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E] | - |
dc.sector.department | DEPARTMENT OF MOLECULAR AND LIFE SCIENCE | - |
dc.identifier.pid | hseo | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.