{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:02:47Z","timestamp":1790197367024,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T00:00:00Z","timestamp":1575936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington disease (HD) is a fatal neurodegenerative disorder without a cure that is caused by an aberrant expansion of CAG repeats in exon 1 of the huntingtin (<jats:italic>HTT<\/jats:italic>) gene. Although a negative correlation between the number of CAG repeats and the age of disease onset is established, additional factors may contribute to the high heterogeneity of the complex manifestation of symptoms among patients. This variability is also observed in mouse models, even under controlled genetic and environmental conditions. To better understand this phenomenon, we analysed the R6\/1 strain in search of potential correlates between pathological motor\/cognitive phenotypical traits and transcriptional alterations. HD-related genes (e.g., <jats:italic>Penk<\/jats:italic>, <jats:italic>Plk5<\/jats:italic>, <jats:italic>Itpka<\/jats:italic>), despite being downregulated across the examined brain areas (the prefrontal cortex, striatum, hippocampus and cerebellum), exhibited tissue-specific correlations with particular phenotypical traits that were attributable to the contribution of the brain region to that trait (e.g., striatum and rotarod performance, cerebellum and feet clasping). Focusing on the striatum, we determined that the transcriptional dysregulation associated with HD was partially exacerbated in mice that showed poor overall phenotypical scores, especially in genes with relevant roles in striatal functioning (e.g., <jats:italic>Pde10a<\/jats:italic>, <jats:italic>Drd1<\/jats:italic>, <jats:italic>Drd2<\/jats:italic>, <jats:italic>Ppp1r1b<\/jats:italic>). However, we also observed transcripts associated with relatively better outcomes, such as <jats:italic>Nfya<\/jats:italic> (CCAAT-binding transcription factor NF-Y subunit A) plus others related to neuronal development, apoptosis and differentiation. In this study, we demonstrated that altered brain transcription can be related to the manifestation of HD-like symptoms in mouse models and that this can be extrapolated to the highly heterogeneous population of HD patients.<\/jats:p>","DOI":"10.1038\/s41598-019-55177-9","type":"journal-article","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T11:03:32Z","timestamp":1575975812000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Transcriptional correlates of the pathological phenotype in a Huntington\u2019s disease mouse model"],"prefix":"10.1038","volume":"9","author":[{"given":"Andrea","family":"Gallardo-Orihuela","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irati","family":"Herv\u00e1s-Corpi\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-5905","authenticated-orcid":false,"given":"Carmen","family":"Hierro-Bujalance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sanchez-Sotano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Jim\u00e9nez-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Mora-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-2153","authenticated-orcid":false,"given":"Antonio","family":"Campos-Caro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Garcia-Alloza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M.","family":"Valor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,10]]},"reference":[{"key":"55177_CR1","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1152\/physrev.00041.2009","volume":"90","author":"C Zuccato","year":"2010","unstructured":"Zuccato, C., Valenza, M. & Cattaneo, E. Molecular mechanisms and potential therapeutical targets in Huntington\u2019s disease. Physiol Rev 90, 905\u2013981 (2010).","journal-title":"Physiol Rev"},{"key":"55177_CR2","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/S1474-4422(13)70088-7","volume":"12","author":"SJ Tabrizi","year":"2013","unstructured":"Tabrizi, S. J. et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington\u2019s disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol 12, 637\u2013649 (2013).","journal-title":"Lancet Neurol"},{"key":"55177_CR3","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/ng0893-398","volume":"4","author":"SE Andrew","year":"1993","unstructured":"Andrew, S. E. et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington\u2019s disease. Nat Genet 4, 398\u2013403 (1993).","journal-title":"Nat Genet"},{"key":"55177_CR4","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1006\/nbdi.1994.0019","volume":"1","author":"F Persichetti","year":"1994","unstructured":"Persichetti, F. et al. Huntington\u2019s disease CAG trinucleotide repeats in pathologically confirmed post-mortem brains. Neurobiol Dis 1, 159\u2013166 (1994).","journal-title":"Neurobiol Dis"},{"issue":"Suppl 1","key":"55177_CR5","doi-asserted-by":"publisher","first-page":"S107","DOI":"10.1016\/S1353-8020(11)70034-7","volume":"18","author":"H Shang","year":"2012","unstructured":"Shang, H., Danek, A., Landwehrmeyer, B. & Burgunder, J. M. Huntington\u2019s disease: new aspects on phenotype and genotype. Parkinsonism Relat Disord 18(Suppl 1), S107\u2013109 (2012).","journal-title":"Parkinsonism Relat Disord"},{"key":"55177_CR6","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S0165-1781(01)00257-8","volume":"102","author":"GE Berrios","year":"2001","unstructured":"Berrios, G. E. et al. Psychiatric symptoms and CAG repeats in neurologically asymptomatic Huntington\u2019s disease gene carriers. Psychiatry Res 102, 217\u2013225 (2001).","journal-title":"Psychiatry Res"},{"key":"55177_CR7","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1136\/jmg.31.11.872","volume":"31","author":"K Kieburtz","year":"1994","unstructured":"Kieburtz, K. et al. Trinucleotide repeat length and progression of illness in Huntington\u2019s disease. J Med Genet 31, 872\u2013874 (1994).","journal-title":"J Med Genet"},{"key":"55177_CR8","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1093\/hmg\/ddr111","volume":"20","author":"PM Gaughwin","year":"2011","unstructured":"Gaughwin, P. M. et al. Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington\u2019s disease. Hum Mol Genet 20, 2225\u20132237 (2011).","journal-title":"Hum Mol Genet"},{"key":"55177_CR9","doi-asserted-by":"publisher","first-page":"11023","DOI":"10.1073\/pnas.0504921102","volume":"102","author":"F Borovecki","year":"2005","unstructured":"Borovecki, F. et al. Genome-wide expression profiling of human blood reveals biomarkers for Huntington\u2019s disease. Proc Natl Acad Sci USA 102, 11023\u201311028 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"55177_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/srep44849","volume":"7","author":"DJ Hensman Moss","year":"2017","unstructured":"Hensman Moss, D. J. et al. Huntington\u2019s disease blood and brain show a common gene expression pattern and share an immune signature with Alzheimer\u2019s disease. Sci Rep 7, 44849 (2017).","journal-title":"Sci Rep"},{"key":"55177_CR11","doi-asserted-by":"publisher","first-page":"17141","DOI":"10.1073\/pnas.1104409108","volume":"108","author":"Y Hu","year":"2011","unstructured":"Hu, Y. et al. Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse. Proc Natl Acad Sci USA 108, 17141\u201317146 (2011).","journal-title":"Proc Natl Acad Sci USA"},{"key":"55177_CR12","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1038\/ejhg.2014.281","volume":"23","author":"A Mastrokolias","year":"2015","unstructured":"Mastrokolias, A. et al. Huntington\u2019s disease biomarker progression profile identified by transcriptome sequencing in peripheral blood. Eur J Hum Genet 23, 1349\u20131356 (2015).","journal-title":"Eur J Hum Genet"},{"key":"55177_CR13","doi-asserted-by":"publisher","first-page":"14424","DOI":"10.1073\/pnas.0703652104","volume":"104","author":"H Runne","year":"2007","unstructured":"Runne, H. et al. Analysis of potential transcriptomic biomarkers for Huntington\u2019s disease in peripheral blood. Proc Natl Acad Sci USA 104, 14424\u201314429 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"55177_CR14","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1007\/s12035-014-8715-8","volume":"51","author":"LM Valor","year":"2015","unstructured":"Valor, L. M. Transcription, epigenetics and ameliorative strategies in Huntington\u2019s Disease: a genome-wide perspective. Mol Neurobiol 51, 406\u2013423 (2015).","journal-title":"Mol Neurobiol"},{"key":"55177_CR15","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.nbd.2011.07.001","volume":"45","author":"T Seredenina","year":"2012","unstructured":"Seredenina, T. & Luthi-Carter, R. What have we learned from gene expression profiles in Huntington\u2019s disease? Neurobiol Dis 45, 83\u201398 (2012).","journal-title":"Neurobiol Dis"},{"key":"55177_CR16","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3233\/JHD-170273","volume":"7","author":"E Silajdzic","year":"2018","unstructured":"Silajdzic, E. & Bjorkqvist, M. A Critical Evaluation of Wet Biomarkers for Huntington\u2019s Disease: Current Status and Ways Forward. J Huntingtons Dis 7, 109\u2013135 (2018).","journal-title":"J Huntingtons Dis"},{"key":"55177_CR17","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.cell.2015.07.003","volume":"162","author":"G.M.O.H.s.D.G.-H. Consortium","year":"2015","unstructured":"Consortium, G. M. O. H. s. D. G.-H. Identification of Genetic Factors that Modify Clinical Onset of Huntington\u2019s Disease. Cell 162, 516\u2013526 (2015).","journal-title":"Cell"},{"key":"55177_CR18","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/S1474-4422(17)30161-8","volume":"16","author":"DJH Moss","year":"2017","unstructured":"Moss, D. J. H. et al. Identification of genetic variants associated with Huntington\u2019s disease progression: a genome-wide association study. Lancet Neurol 16, 701\u2013711 (2017).","journal-title":"Lancet Neurol"},{"key":"55177_CR19","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1093\/hmg\/ddm133","volume":"16","author":"A Kuhn","year":"2007","unstructured":"Kuhn, A. et al. Mutant huntingtin\u2019s effects on striatal gene expression in mice recapitulate changes observed in human Huntington\u2019s disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum Mol Genet 16, 1845\u20131861 (2007).","journal-title":"Hum Mol Genet"},{"key":"55177_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28185-4","volume":"8","author":"I Hervas-Corpion","year":"2018","unstructured":"Hervas-Corpion, I. et al. Early alteration of epigenetic-related transcription in Huntington\u2019s disease mouse models. Sci Rep 8, 9925 (2018).","journal-title":"Sci Rep"},{"key":"55177_CR21","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nn.4256","volume":"19","author":"P Langfelder","year":"2016","unstructured":"Langfelder, P. et al. Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice. Nat Neurosci 19, 623\u2013633 (2016).","journal-title":"Nat Neurosci"},{"key":"55177_CR22","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/j.1601-183X.2007.00350.x","volume":"7","author":"A Hodges","year":"2008","unstructured":"Hodges, A. et al. Brain gene expression correlates with changes in behavior in the R6\/1 mouse model of Huntington\u2019s disease. Genes Brain Behav 7, 288\u2013299 (2008).","journal-title":"Genes Brain Behav"},{"key":"55177_CR23","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.nbd.2016.02.004","volume":"89","author":"D Guiretti","year":"2016","unstructured":"Guiretti, D. et al. Specific promoter deacetylation of histone H3 is conserved across mouse models of Huntington\u2019s disease in the absence of bulk changes. Neurobiol Dis 89, 190\u2013201 (2016).","journal-title":"Neurobiol Dis"},{"key":"55177_CR24","doi-asserted-by":"publisher","first-page":"10471","DOI":"10.1523\/JNEUROSCI.0670-13.2013","volume":"33","author":"LM Valor","year":"2013","unstructured":"Valor, L. M. et al.\u00a0Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease. J Neurosci\u00a033, 10471\u201382 (2013).","journal-title":"J Neurosci"},{"key":"55177_CR25","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41580-018-0089-8","volume":"20","author":"R Singh","year":"2019","unstructured":"Singh, R., Letai, A. & Sarosiek, K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol 20, 175\u2013193 (2019).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"55177_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.300","volume":"4","author":"J Sassone","year":"2013","unstructured":"Sassone, J., Maraschi, A., Sassone, F., Silani, V. & Ciammola, A. Defining the role of the Bcl-2 family proteins in Huntington\u2019s disease. Cell Death Dis 4, e772 (2013).","journal-title":"Cell Death Dis"},{"key":"55177_CR27","doi-asserted-by":"publisher","first-page":"e1003051","DOI":"10.1371\/journal.pgen.1003051","volume":"8","author":"AV Goula","year":"2012","unstructured":"Goula, A. V. et al. Transcription elongation and tissue-specific somatic CAG instability. PLoS Genet 8, e1003051 (2012).","journal-title":"PLoS Genet"},{"key":"55177_CR28","doi-asserted-by":"publisher","first-page":"e23647","DOI":"10.1371\/journal.pone.0023647","volume":"6","author":"JM Lee","year":"2011","unstructured":"Lee, J. M., Pinto, R. M., Gillis, T., St Claire, J. C. & Wheeler, V. C. Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver. PLoS One 6, e23647 (2011).","journal-title":"PLoS One"},{"key":"55177_CR29","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/emboj.2008.23","volume":"27","author":"T Yamanaka","year":"2008","unstructured":"Yamanaka, T. et al. Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor. EMBO J 27, 827\u2013839 (2008).","journal-title":"EMBO J"},{"key":"55177_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4354","volume":"5","author":"T Yamanaka","year":"2014","unstructured":"Yamanaka, T. et al. NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization. Nat Commun 5, 3354 (2014).","journal-title":"Nat Commun"},{"key":"55177_CR31","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/emboj.2011.400","volume":"31","author":"PF Durieux","year":"2012","unstructured":"Durieux, P. F., Schiffmann, S. N. & de Kerchove d\u2019Exaerde, A. Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions. EMBO J 31, 640\u2013653 (2012).","journal-title":"EMBO J"},{"key":"55177_CR32","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.neuro.2008.02.014","volume":"29","author":"Y Liu","year":"2008","unstructured":"Liu, Y. et al. Endotoxin induces a delayed loss of TH-IR neurons in substantia nigra and motor behavioral deficits. Neurotoxicology 29, 864\u2013870 (2008).","journal-title":"Neurotoxicology"},{"key":"55177_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/srep29967","volume":"6","author":"G Perruolo","year":"2016","unstructured":"Perruolo, G. et al. Parkinson-like phenotype in insulin-resistant PED\/PEA-15 transgenic mice. Sci Rep 6, 29967 (2016).","journal-title":"Sci Rep"},{"key":"55177_CR34","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1093\/hmg\/ddu736","volume":"24","author":"AA Adebola","year":"2015","unstructured":"Adebola, A. A. et al. Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth Type 2E phenotype. Hum Mol Genet 24, 2163\u20132174 (2015).","journal-title":"Hum Mol Genet"},{"key":"55177_CR35","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.brainresrev.2011.02.005","volume":"67","author":"R Lalonde","year":"2011","unstructured":"Lalonde, R. & Strazielle, C. Brain regions and genes affecting limb-clasping responses. Brain Res Rev 67, 252\u2013259 (2011).","journal-title":"Brain Res Rev"},{"key":"55177_CR36","doi-asserted-by":"publisher","first-page":"10721","DOI":"10.1523\/JNEUROSCI.6413-10.2011","volume":"31","author":"GR Barker","year":"2011","unstructured":"Barker, G. R. & Warburton, E. C. When is the hippocampus involved in recognition memory? J Neurosci 31, 10721\u201310731 (2011).","journal-title":"J Neurosci"},{"key":"55177_CR37","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1242\/dmm.026609","volume":"10","author":"K Timper","year":"2017","unstructured":"Timper, K. & Bruning, J. C. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis Model Mech 10, 679\u2013689 (2017).","journal-title":"Dis Model Mech"},{"key":"55177_CR38","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3389\/fpsyt.2017.00297","volume":"8","author":"HM Dorton","year":"2017","unstructured":"Dorton, H. M., Luo, S., Monterosso, J. R. & Page, K. A. Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response. Front Psychiatry 8, 297 (2017).","journal-title":"Front Psychiatry"},{"key":"55177_CR39","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1006\/exnr.1999.7327","volume":"162","author":"L Menalled","year":"2000","unstructured":"Menalled, L. et al. Decrease in striatal enkephalin mRNA in mouse models of Huntington\u2019s disease. Exp Neurol 162, 328\u2013342 (2000).","journal-title":"Exp Neurol"},{"key":"55177_CR40","doi-asserted-by":"publisher","first-page":"e75099","DOI":"10.1371\/journal.pone.0075099","volume":"8","author":"S Bissonnette","year":"2013","unstructured":"Bissonnette, S., Vaillancourt, M., Hebert, S. S., Drolet, G. & Samadi, P. Striatal pre-enkephalin overexpression improves Huntington\u2019s disease symptoms in the R6\/2 mouse model of Huntington\u2019s disease. PLoS One 8, e75099 (2013).","journal-title":"PLoS One"},{"key":"55177_CR41","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.2174\/1381612053507459","volume":"11","author":"U Barry","year":"2005","unstructured":"Barry, U. & Zuo, Z. Opioids: old drugs for potential new applications. Curr Pharm Des 11, 1343\u20131350 (2005).","journal-title":"Curr Pharm Des"},{"key":"55177_CR42","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3233\/JHD-2012-120009","volume":"1","author":"L Galvan","year":"2012","unstructured":"Galvan, L., Andre, V. M., Wang, E. A., Cepeda, C. & Levine, M. S. Functional Differences Between Direct and Indirect Striatal Output Pathways in Huntington\u2019s Disease. J Huntingtons Dis 1, 17\u201325 (2012).","journal-title":"J Huntingtons Dis"},{"key":"55177_CR43","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/nrm2395","volume":"9","author":"T Riley","year":"2008","unstructured":"Riley, T., Sontag, E., Chen, P. & Levine, A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 9, 402\u2013412 (2008).","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"11","key":"55177_CR44","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1038\/s41418-019-0285-x","volume":"26","author":"Beatriz del Blanco","year":"2019","unstructured":"Del Blanco, B. et al. CBP and SRF co-regulate dendritic growth and synaptic maturation. Cell Death Differ\u00a026, 2208\u20132222 (2019).","journal-title":"Cell Death & Differentiation"},{"key":"55177_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S1751731110001667","volume":"5","author":"J Casellas","year":"2011","unstructured":"Casellas, J. Inbred mouse strains and genetic stability: a review. Animal 5, 1\u20137 (2011).","journal-title":"Animal"},{"key":"55177_CR46","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.neuropharm.2013.10.025","volume":"80","author":"LM Valor","year":"2014","unstructured":"Valor, L. M. & Guiretti, D. What\u2019s wrong with epigenetics in Huntington\u2019s disease? Neuropharmacology 80, 103\u2013114 (2014).","journal-title":"Neuropharmacology"},{"key":"55177_CR47","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3389\/fnhum.2017.00017","volume":"11","author":"L Francelle","year":"2017","unstructured":"Francelle, L., Lotz, C., Outeiro, T., Brouillet, E. & Merienne, K. Contribution of Neuroepigenetics to Huntington\u2019s Disease. Front Hum Neurosci 11, 17 (2017).","journal-title":"Front Hum Neurosci"},{"key":"55177_CR48","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","volume":"87","author":"L Mangiarini","year":"1996","unstructured":"Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493\u2013506 (1996).","journal-title":"Cell"},{"key":"55177_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-49612-0","volume":"9","author":"JA Varholick","year":"2019","unstructured":"Varholick, J. A. et al. Social dominance hierarchy type and rank contribute to phenotypic variation within cages of laboratory mice. Sci Rep 9, 13650 (2019).","journal-title":"Sci Rep"},{"key":"55177_CR50","doi-asserted-by":"publisher","first-page":"6995","DOI":"10.1096\/fj.201801600R","volume":"33","author":"A Palle","year":"2019","unstructured":"Palle, A. et al. Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety-like behavior. FASEB J 33, 6995\u20137008 (2019).","journal-title":"FASEB J"},{"key":"55177_CR51","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.psyneuen.2015.12.001","volume":"65","author":"C Infante-Garcia","year":"2016","unstructured":"Infante-Garcia, C., Ramos-Rodriguez, J. J., Galindo-Gonzalez, L. & Garcia-Alloza, M. Long-term central pathology and cognitive impairment are exacerbated in a mixed model of Alzheimer\u2019s disease and type 2 diabetes. Psychoneuroendocrinology 65, 15\u201325 (2016).","journal-title":"Psychoneuroendocrinology"},{"key":"55177_CR52","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.nlm.2005.07.002","volume":"84","author":"E Dere","year":"2005","unstructured":"Dere, E., Huston, J. P. & De Souza Silva, M. A. Integrated memory for objects, places, and temporal order: evidence for episodic-like memory in mice. Neurobiol Learn Mem 84, 214\u2013221 (2005).","journal-title":"Neurobiol Learn Mem"},{"key":"55177_CR53","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1038\/cdd.2010.40","volume":"17","author":"LM Valor","year":"2010","unstructured":"Valor, L. M., Jancic, D., Lujan, R. & Barco, A. Ultrastructural and transcriptional profiling of neuropathological misregulation of CREB function. Cell Death Differ 17, 1636\u20131644 (2010).","journal-title":"Cell Death Differ"},{"key":"55177_CR54","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1016\/j.bbadis.2016.05.024","volume":"1862","author":"AI Arroba","year":"2016","unstructured":"Arroba, A. I. et al. Modulation of microglia polarization dynamics during diabetic retinopathy in db\/db mice. Biochim Biophys Acta 1862, 1663\u20131674 (2016).","journal-title":"Biochim Biophys Acta"},{"key":"55177_CR55","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.ymthe.2017.08.014","volume":"26","author":"C Amatya","year":"2018","unstructured":"Amatya, C., Radichev, I. A., Ellefson, J., Williams, M. & Savinov, A. Y. Self-Transducible Bimodal PDX1-FOXP3 Protein Lifts Insulin Secretion and Curbs Autoimmunity, Boosting Tregs in Type 1 Diabetic Mice. Mol Ther 26, 184\u2013198 (2018).","journal-title":"Mol Ther"},{"key":"55177_CR56","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.1093\/cercor\/bhp004","volume":"19","author":"D Jancic","year":"2009","unstructured":"Jancic, D., de Armentia, L., Valor, M., Olivares, L. M. & Barco, R. A. Inhibition of cAMP response element-binding protein reduces neuronal excitability and plasticity, and triggers neurodegeneration. Cereb Cortex 19, 2535\u20132547 (2009).","journal-title":"Cereb Cortex"},{"key":"55177_CR57","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1210\/en.2016-1807","volume":"158","author":"CA Maguire","year":"2017","unstructured":"Maguire, C. A. et al. Tac1 Signaling Is Required for Sexual Maturation and Responsiveness of GnRH Neurons to Kisspeptin in the Male Mouse. Endocrinology 158, 2319\u20132329 (2017).","journal-title":"Endocrinology"},{"key":"55177_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7920","volume":"6","author":"PC Cook","year":"2015","unstructured":"Cook, P. C. et al. A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nat Commun 6, 6920 (2015).","journal-title":"Nat Commun"},{"key":"55177_CR59","doi-asserted-by":"publisher","first-page":"e1001242","DOI":"10.1371\/journal.pgen.1001242","volume":"6","author":"L Mollersen","year":"2010","unstructured":"Mollersen, L., Rowe, A. D., Larsen, E., Rognes, T. & Klungland, A. Continuous and periodic expansion of CAG repeats in Huntington\u2019s disease R6\/1 mice. PLoS Genet 6, e1001242 (2010).","journal-title":"PLoS Genet"},{"key":"55177_CR60","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq. 2. Genome Biol 15, 550 (2014).","journal-title":"Genome Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55177-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55177-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55177-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T17:05:54Z","timestamp":1671296754000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55177-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,10]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["55177"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-55177-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,10]]},"assertion":[{"value":"22 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18696"}}