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Whether and how the causative gene\n                    <jats:italic>WFS1<\/jats:italic>\n                    deficiency affects synapse formation remain elusive. By mirroring human brain development with cerebral organoids,\n                    <jats:italic>WFS1<\/jats:italic>\n                    -deficient cerebral organoids not only recapitulate the neuronal loss in WS patients, but also exhibit significantly impaired synapse formation and function associated with reduced astrocytes.\n                    <jats:italic>WFS1<\/jats:italic>\n                    deficiency in neurons autonomously delays neuronal differentiation with altered expressions of genes associated with psychiatric disorders, and impairs neurite outgrowth and synapse formation with elevated cytosolic calcium. Intriguingly,\n                    <jats:italic>WFS1<\/jats:italic>\n                    deficiency in astrocytes decreases the expression of glutamate transporter\n                    <jats:italic>EAAT2<\/jats:italic>\n                    by NF-\u03baB activation and induces excessive glutamate. When co-cultured with wildtype neurons,\n                    <jats:italic>WFS1<\/jats:italic>\n                    -deficient astrocytes lead to impaired neurite outgrowth and increased cytosolic calcium in neurons. Importantly, disrupted synapse formation and function in\n                    <jats:italic>WFS1<\/jats:italic>\n                    -deficient cerebral organoids and impaired neurite outgrowth affected by\n                    <jats:italic>WFS1<\/jats:italic>\n                    -deficient astrocytes are efficiently reversed with Riluzole treatment, by restoring\n                    <jats:italic>EAAT2<\/jats:italic>\n                    expression in astrocytes. Furthermore, Riluzole rescues the depressive-like behavior in the forced swimming test and the impaired recognition and spatial memory in the novel object test and water maze test in\n                    <jats:italic>Wfs1<\/jats:italic>\n                    conditional knockout mice. Altogether, our study provides novel insights into how\n                    <jats:italic>WFS1<\/jats:italic>\n                    deficiency affects synapse formation and function, and offers a strategy to treat this disease.\n                  <\/jats:p>","DOI":"10.1038\/s41380-023-01987-3","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T06:03:45Z","timestamp":1675749825000},"page":"1557-1570","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule"],"prefix":"10.1038","volume":"28","author":[{"given":"Fei","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-9090","authenticated-orcid":false,"given":"Yana","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxue","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mushan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhejin","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-6134","authenticated-orcid":false,"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaicheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4934-4360","authenticated-orcid":false,"given":"Zhen","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-7104","authenticated-orcid":false,"given":"Zhen-Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6578-6321","authenticated-orcid":false,"given":"Weida","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"1987_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/2441","volume":"20","author":"H Inoue","year":"1998","unstructured":"Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E, et al. 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