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A rotarod deficit was not present in Q175 mice until 18\u2009months, but increased open field turn rate (reflecting hyperkinesia) and open field anxiety were evident at 6 months. No loss of striatal neurons was seen out to 18\u2009months, but ENK+ and DARPP32+ striatal perikarya were fewer by 6 months, due to diminished expression, with further decline by 18\u2009months. No reduction in SP+ striatal perikarya or striatal interneurons was seen in Q175 mice at 18 months, but cholinergic interneurons showed dendrite attenuation by 6 months. Despite reduced ENK expression in indirect pathway striatal perikarya, ENK\u2010immunostained terminals in globus pallidus externus (GPe) were more abundant at 6 months and remained so out to 18\u2009months. Similarly, SP\u2010immunostained terminals from striatal direct pathway neurons were more abundant in globus pallidus internus and substantia nigra at 6 months and remained so at 18\u2009months. FoxP2+ arkypallidal GPe neurons and subthalamic nucleus neurons were lost by 18\u2009months but not prototypical PARV+ GPe neurons or dopaminergic nigral neurons. Our results show that striatal projection neuron abnormalities and behavioral abnormalities reflecting them develop between 2 and 6 months of age in Q175 male heterozygotes, indicating early effects of the HD mutation. The striatal pathologies resemble those in human HD, but are less severe at 18\u2009months than even in premanifest HD.<\/jats:p>","DOI":"10.1002\/cne.25023","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T12:18:58Z","timestamp":1598962738000},"page":"1327-1371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Progression of basal ganglia pathology in heterozygous\n                    <scp>Q175<\/scp>\n                    knock\u2010in Huntington's disease mice"],"prefix":"10.1002","volume":"529","author":[{"given":"Yunping","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Joni","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika","family":"Sekhri","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-5232","authenticated-orcid":false,"given":"Anton","family":"Reiner","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology The University of Tennessee Health Science Center  Memphis Tennessee USA"},{"name":"Department of Ophthalmology The University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4662-14.2015"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.141"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23889"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300406"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310412"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270403"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(89)90074-X"},{"key":"e_1_2_10_9_1","first-page":"1923","article-title":"Abnormalities of striatal projection neurons and N\u2010methyl\u2010D\u2010aspartate receptors in presymptomatic Huntington's disease","volume":"332","author":"Albin R. 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