{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:11:55Z","timestamp":1791241915948,"version":"4.1.0"},"posted":{"date-parts":[[2025,9,30]]},"group-title":"Neuroscience","reference-count":101,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG061894"],"award-info":[{"award-number":["R01AG061894"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  MicroRNA dysregulation is implicated in neurodegenerative disorders, including Alzheimer\u2019s disease (AD). The role of neuronal microRNA155 (miR155), elevated in both AD and Down syndrome (DS), remains unknown. We found that\n                  <jats:italic>MIR155HG<\/jats:italic>\n                  (miR155 host gene) colocalizes with\n                  <jats:italic>APP<\/jats:italic>\n                  (amyloid-beta precursor protein) in a neuron-specific, topologically-associated domain (TAD) within a regulatory network, in the obligate portion of chromosome 21 triplicated in DS which causes AD neuropathology and in most cases, dementia. We investigated miR155 role during neuron development and then validated these findings in an amyloidopathy model. In human induced pluripotent stem cell (hiPSC)-derived neural stem cells (NSCs), cortical neurons and cortical organoids,\n                  <jats:italic>MIR155<\/jats:italic>\n                  deletion enhanced NSC proliferation, ventral patterning and GABAergic interneuron generation. However,\n                  <jats:italic>MIR155<\/jats:italic>\n                  overexpression inhibited NSC marker expression and GABAergic interneuron generation.\n                  <jats:italic>MIR155<\/jats:italic>\n                  upregulates its mRNA targets,\n                  <jats:italic>NR2F1<\/jats:italic>\n                  \/\n                  <jats:italic>2<\/jats:italic>\n                  , key modulators of hippocampal GABAergic interneuron development. In an amyloidopathy mouse model,\n                  <jats:italic>miR155<\/jats:italic>\n                  deletion induced the expansion of hippocampal NSCs and increased hippocampal GABAergic interneurons. These findings reveal previously unrecognized miR155 roles in NSC dynamics and GABAergic interneuron development which directionally diverge from extensively studied microglial miR155 in their beneficial vs negative impact on AD mouse models, suggesting that approaching miR155 therapeutically may require balancing the effects in neurons and microglia.\n                <\/jats:p>","DOI":"10.1101\/2025.09.28.679053","type":"posted-content","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:00:16Z","timestamp":1759248016000},"source":"Crossref","is-referenced-by-count":1,"title":["miR155 triplicated in Down syndrome regulates hippocampal GABAergic neurogenesis in Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"given":"Xiaodong","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Vianney","family":"Haure-Mirande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mesude","family":"Bicak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Kruglikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Al-subaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Fossati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Noggle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Gandy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100305400453000_2025.09.28.679053v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1958"},{"key":"2025100305400453000_2025.09.28.679053v1.2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1982.00510230035010"},{"key":"2025100305400453000_2025.09.28.679053v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"2025100305400453000_2025.09.28.679053v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.03.002"},{"key":"2025100305400453000_2025.09.28.679053v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01166-7"},{"key":"2025100305400453000_2025.09.28.679053v1.6","doi-asserted-by":"crossref","first-page":"S161","DOI":"10.3233\/JAD-179939","article-title":"Religious Orders Study and Rush Memory and Aging Project","volume":"64","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"2025100305400453000_2025.09.28.679053v1.7","first-page":"621","article-title":"[Morphology of Alzheimer disease]","volume":"108","year":"1990","journal-title":"Fortschr Med"},{"key":"2025100305400453000_2025.09.28.679053v1.8","first-page":"11","article-title":"Down syndrome and microRNAs","volume":"8","year":"2018","journal-title":"Biomed Rep"},{"key":"2025100305400453000_2025.09.28.679053v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/S41583-018-0057-5"},{"key":"2025100305400453000_2025.09.28.679053v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14149"},{"key":"2025100305400453000_2025.09.28.679053v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01356-x"},{"key":"2025100305400453000_2025.09.28.679053v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1529"},{"key":"2025100305400453000_2025.09.28.679053v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"2025100305400453000_2025.09.28.679053v1.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909167106"},{"key":"2025100305400453000_2025.09.28.679053v1.15","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00103"},{"key":"2025100305400453000_2025.09.28.679053v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/nature11082"},{"key":"2025100305400453000_2025.09.28.679053v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90536-7"},{"key":"2025100305400453000_2025.09.28.679053v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/3305"},{"key":"2025100305400453000_2025.09.28.679053v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.03.014"},{"key":"2025100305400453000_2025.09.28.679053v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13260-9"},{"key":"2025100305400453000_2025.09.28.679053v1.21","unstructured":"Gabitto MI Travaglini KJ Rachleff VM Kaplan ES Long B Ariza J Ding Y Mahoney JT Dee N Goldy J et al. 2024. 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