| Publikationstyp: | Beitrag in wissenschaftlicher Zeitschrift |
| Art der Begutachtung: | Peer review (Publikation) |
| Titel: | Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry |
| Autor/-in: | Runne, Heike Régulier, Etienne Kuhn, Alexandre Zala, Diana Gokce, Ozgun Perrin, Valérie Sick, Beate Aebischer, Patrick Déglon, Nicole Luthi-Carter, Ruth |
| DOI: | 10.1523/JNEUROSCI.3044-08.2008 |
| Erschienen in: | Journal of Neuroscience |
| Band(Heft): | 28 |
| Heft: | 39 |
| Seite(n): | 9723 |
| Seiten bis: | 9731 |
| Erscheinungsdatum: | 2008 |
| Verlag / Hrsg. Institution: | Society for Neuroscience |
| ISSN: | 1529-2401 0270-6474 |
| Sprache: | Englisch |
| Fachgebiet (DDC): | 572: Biochemie |
| Zusammenfassung: | Gene expression changes are a hallmark of the neuropathology of Huntington's disease (HD), but the exact molecular mechanisms of this effect remain uncertain. Here, we report that in vitro models of disease comprised of primary striatal neurons expressing N-terminal fragments of mutant huntingtin (via lentiviral gene delivery) faithfully reproduce the gene expression changes seen in human HD. Neither viral infection nor unrelated (enhanced green fluorescent protein) transgene expression had a major effect on resultant RNA profiles. Expression of a wild-type fragment of huntingtin [htt171-18Q] also caused only a small number of RNA changes. The disease-related signal in htt171-82Q versus htt171-18Q comparisons was far greater, resulting in the differential detection of 20% of all mRNA probe sets. Transcriptomic effects of mutated htt171 are time- and polyglutamine-length dependent and occur in parallel with other manifestations of polyglutamine toxicity over 4-8 weeks. Specific RNA changes in htt171-82Q-expressing striatal cells accurately recapitulated those observed in human HD caudate and included decreases in PENK (proenkephalin), RGS4 (regulator of G-protein signaling 4), dopamine D(1) receptor (DRD1), DRD2, CNR1 (cannabinoid CB(1) receptor), and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32; also known as PPP1R1B) mRNAs. HD-related transcriptomic changes were also observed in primary neurons expressing a longer fragment of mutant huntingtin (htt853-82Q). The gene expression changes observed in cultured striatal neurons are not secondary to abnormalities of neuronal firing or glutamatergic, dopaminergic, or brain-derived neurotrophic factor signaling, thereby demonstrating that HD-induced dysregulation of the striatal transcriptome might be attributed to intrinsic effects of mutant huntingtin. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/14044 |
| Volltext Version: | Publizierte Version |
| Lizenz (gemäss Verlagsvertrag): | Lizenz gemäss Verlagsvertrag |
| Departement: | School of Engineering |
| Organisationseinheit: | Institut für Datenanalyse und Prozessdesign (IDP) |
| Enthalten in den Sammlungen: | Publikationen School of Engineering |
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Runne, H., Régulier, E., Kuhn, A., Zala, D., Gokce, O., Perrin, V., Sick, B., Aebischer, P., Déglon, N., & Luthi-Carter, R. (2008). Dysregulation of gene expression in primary neuron models of Huntington’s disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry. Journal of Neuroscience, 28(39), 9723–9731. https://doi.org/10.1523/JNEUROSCI.3044-08.2008
Runne, H. et al. (2008) ‘Dysregulation of gene expression in primary neuron models of Huntington’s disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry’, Journal of Neuroscience, 28(39), pp. 9723–9731. Available at: https://doi.org/10.1523/JNEUROSCI.3044-08.2008.
H. Runne et al., “Dysregulation of gene expression in primary neuron models of Huntington’s disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry,” Journal of Neuroscience, vol. 28, no. 39, pp. 9723–9731, 2008, doi: 10.1523/JNEUROSCI.3044-08.2008.
RUNNE, Heike, Etienne RÉGULIER, Alexandre KUHN, Diana ZALA, Ozgun GOKCE, Valérie PERRIN, Beate SICK, Patrick AEBISCHER, Nicole DÉGLON und Ruth LUTHI-CARTER, 2008. Dysregulation of gene expression in primary neuron models of Huntington’s disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry. Journal of Neuroscience. 2008. Bd. 28, Nr. 39, S. 9723–9731. DOI 10.1523/JNEUROSCI.3044-08.2008
Runne, Heike, Etienne Régulier, Alexandre Kuhn, Diana Zala, Ozgun Gokce, Valérie Perrin, Beate Sick, Patrick Aebischer, Nicole Déglon, and Ruth Luthi-Carter. 2008. “Dysregulation of Gene Expression in Primary Neuron Models of Huntington’s Disease Shows That Polyglutamine-Related Effects on the Striatal Transcriptome May Not Be Dependent on Brain Circuitry.” Journal of Neuroscience 28 (39): 9723–31. https://doi.org/10.1523/JNEUROSCI.3044-08.2008.
Runne, Heike, et al. “Dysregulation of Gene Expression in Primary Neuron Models of Huntington’s Disease Shows That Polyglutamine-Related Effects on the Striatal Transcriptome May Not Be Dependent on Brain Circuitry.” Journal of Neuroscience, vol. 28, no. 39, 2008, pp. 9723–31, https://doi.org/10.1523/JNEUROSCI.3044-08.2008.
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