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Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection

Title
Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection
Author
서혜명
Keywords
polymerase chain reaction; cell culture techniques; gene expression; calcitonin gene-related peptide; gene expression profiling; genes; insulin-like growth factor i; midbrain; neurons; toxins; mice; toxic effect; laser capture microdissection; pituitary adenylate cyclase activating polypeptide; dopaminergic neurons; emotional vulnerability; molecule
Issue Date
2005-05
Publisher
OXFORD UNIV PRESS
Citation
HUMAN MOLECULAR GENETICS, v. 14, No. 13, Page. 1709-1725
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.
URI
https://academic.oup.com/hmg/article/14/13/1709/621031http://repository.hanyang.ac.kr/handle/20.500.11754/110623
ISSN
0964-6906; 1460-2083
DOI
10.1093/hmg/ddi178
Appears in Collections:
COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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