Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/11624
Title: Transcriptional dysregulation in striatal projection- and interneurons in a mouse model of Huntington's disease: neuronal selectivity and potential neuroprotective role of HAP1.
Authors: Zucker, B
Luthi-Carter, R
Kama, JA
Dunah, AW
Stern, EA
Fox, JH
Standaert, DG
Young, AB
Augood, SJ
First Published: 15-Jan-2005
Citation: HUM MOL GENET, 2005, 14 (2), pp. 179-189
Abstract: Transcriptional dysregulation has been described as a central mechanism in the pathogenesis of Huntington's disease (HD), in which medium spiny projection neurons (MSN) selectively degenerate whereas neuronal nitric-oxide-synthase-positive interneurons (nNOS-IN) survive. In order to begin to understand this differential vulnerability we compared mRNA levels of selected genes involved in N-methyl-D-aspartate (NMDA) glutamate receptor and calcium (Ca2+) signaling pathways in MSN and nNOS-IN from 12-week-old R6/2 mice, a transgenic mouse model of HD and wild-type littermates. We undertook a laser capture microdissection (LCM) study to examine the contribution of transcriptional dysregulation in candidate genes involved in these two signaling pathways in discrete populations of striatal neurons. The use of LCM in combination with quantitative real-time polymerase chain reaction (Q-PCR) allowed us to quantify the neuronal abundance of candidate mRNAs. We found different transcriptional alterations in R6/2 neurons for both MSN and nNOS-IN, indicating that global transcriptional dysregulation alone does not account for selective vulnerability. Further, we observed a striking enrichment of several mRNAs in the nNOS-IN population, including that for the NMDA receptor subunit NR2D, the postsynaptic density protein 95 (PSD-95) and the huntingtin-associated protein 1 (HAP1) as well as nitric-oxide-synthase (nNOS) mRNA itself. The higher expression levels of these molecules in nNOS-IN when compared with MSN together with an association of nNOS, NR2D and HAP1 in a protein complex with PSD-95 suggest that these proteins may be involved in protective pathways that contribute to the resistance of this interneuron population to neurodegeneration in HD.
DOI Link: 10.1093/hmg/ddi014
ISSN: 0964-6906
Links: http://hdl.handle.net/2381/11624
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

Files in This Item:
There are no files associated with this item.


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.