{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:04:08Z","timestamp":1793351048267,"version":"4.5.0"},"reference-count":84,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CHDI contract awards","award":["A-10404"],"award-info":[{"award-number":["A-10404"]}]},{"name":"multiple generous donors","award":["A-10404"],"award-info":[{"award-number":["A-10404"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Boosting trophic support to striatal neurons by increasing levels of brain-derived neurotrophic factor (BDNF) has been considered as a target for therapeutic intervention for several neurodegenerative diseases, including Huntington\u2019s disease (HD). To aid in the implementation of such a strategy, a thorough understanding of BDNF cortical\u2013striatal transport is critical to help guide its strategic delivery. In this manuscript, we investigate the dynamic behavior of BDNF transport along the cortical\u2013striatal axis in Q140 primary neurons, a mouse model for HD. We examine this by using single-molecule labeling of BDNF conjugated with quantum dots (QD-BDNF) to follow the transport along the cortical\u2013striatal axis in a microfluidic chamber system specifically designed for the co-culture of cortical and striatal primary neurons. Using this approach, we observe a defect of QD-BDNF transport in Q140 neurons. Our study demonstrates that QD-BDNF transport along the cortical\u2013striatal axis involves the impairment of anterograde transport within axons of cortical neurons, and of retrograde transport within dendrites of striatal neurons. One prominent feature we observe is the extended pause time of QD-BDNF retrograde transport within Q140 striatal dendrites. Taken together, these finding support the hypothesis that delinquent spatiotemporal trophic support of BDNF to striatal neurons, driven by impaired transport, may contribute to the pathogenesis of HD, providing us with insight into how a BDNF supplementation therapeutic strategy may best be applied for HD.<\/jats:p>","DOI":"10.3390\/biology12020157","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T07:57:38Z","timestamp":1674115058000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Failure to Thrive: Impaired BDNF Transport along the Cortical\u2013Striatal Axis in Mouse Q140 Neurons of Huntington\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Michael T.","family":"Maloney","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-047X","authenticated-orcid":false,"given":"Sumana","family":"Bhowmick","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Millan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mridu","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everett","family":"Frost","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Y.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia Bora","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle Y.","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-5165","authenticated-orcid":false,"given":"Yanmin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 1201 Welch Road, MSLS, P259, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Irfan, Z., Khanam, S., Karmakar, V., Firdous, S.M., Samih, B., Abou, I., Khier, E., Khan, I., Rehman, M.U., and Khan, A. 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