{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:58Z","timestamp":1785413698995,"version":"3.56.0"},"posted":{"date-parts":[[2025,9,21]]},"group-title":"Neuroscience","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["NS096098"],"award-info":[{"award-number":["NS096098"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21MH132839"],"award-info":[{"award-number":["R21MH132839"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AR220067"],"award-info":[{"award-number":["AR220067"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Pigment epithelial-derived factor (PEDF) is a multifunctional protein produced predominantly by the retinal pigment epithelium and expressed in many tissues, including the brain, highlighting its participation in crucial processes, such as neuroprotection and angiogenesis. Some neurodevelopmental disorders, such as ASD, are characterized by neurodevelopmental abnormalities, including altered neurite formation, spine formation, and neuronal activities. Many efforts have been made to resolve NDDs, but until now, some symptoms remain untargeted. PEDF is involved in many steps of neurodevelopment. The treatment of PEDF peptide might improve the outcome of NDD symptoms by altering neuronal morphologies. We used PEDF peptides that contain different functional domains to study the effect of administering PEDF peptides on neuronal morphology in a prenatal valproic acid (VPA)-exposed mouse model. We identified that treatment with PEDF peptides rectified the abnormalities in neurite formation and spine formation in VPA-exposed cortical neurons.\n                  <jats:italic>In vitro<\/jats:italic>\n                  calcium imaging showed abnormalities in spontaneous activity in VPA-exposed cortical neurons. Treatment of a short PEDF peptide normalized the intracellular calcium response to the control level. Accordingly, PEDF peptides have the prospect of serving as potential treatments for patients with neurodevelopmental disorders, such as ASD.\n                <\/jats:p>","DOI":"10.1101\/2025.09.20.677502","type":"posted-content","created":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T16:45:15Z","timestamp":1758473115000},"source":"Crossref","is-referenced-by-count":0,"title":["PEDF peptides rescue defects in neurite morphogenesis and intracellular calcium response in cortical neurons from mice exposed to valproic acid"],"prefix":"10.64898","author":[{"given":"Xiaonan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0173-0430","authenticated-orcid":false,"given":"Kazuhito","family":"Toyo-oka","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070411350950000_2025.09.20.677502v2.1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2012.14.3\/pchaste"},{"key":"2026070411350950000_2025.09.20.677502v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.41"},{"key":"2026070411350950000_2025.09.20.677502v2.3","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/ajmg.b.32631","article-title":"Epigenetics and autism spectrum disorder: A report of an autism case with mutation in H1 linker histone HIST1H1E and literature review","volume":"177","year":"2018","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"2026070411350950000_2025.09.20.677502v2.4","doi-asserted-by":"crossref","first-page":"e855","DOI":"10.1038\/tp.2016.120","article-title":"Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders","volume":"6","year":"2016","journal-title":"Transl Psychiatry"},{"key":"2026070411350950000_2025.09.20.677502v2.5","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fgene.2018.00080","article-title":"Neurodevelopmental Genetic Diseases Associated With Microdeletions and Microduplications of Chromosome 17p13.3","volume":"9","year":"2018","journal-title":"Front Genet"},{"key":"2026070411350950000_2025.09.20.677502v2.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-21-09378.2002"},{"key":"2026070411350950000_2025.09.20.677502v2.7","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2012.00008"},{"key":"2026070411350950000_2025.09.20.677502v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/srep05637"},{"key":"2026070411350950000_2025.09.20.677502v2.9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jcmgh.2015.06.006","article-title":"Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt\/\u03b2-catenin Signaling in the Liver","volume":"1","year":"2015","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"2026070411350950000_2025.09.20.677502v2.10","first-page":"219","article-title":"Inhibition of tumor cell surface ATP synthesis by pigment epithelium-derived factor: implications for antitumor activity","volume":"41","year":"2012","journal-title":"Int J Oncol"},{"key":"2026070411350950000_2025.09.20.677502v2.11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05401"},{"key":"2026070411350950000_2025.09.20.677502v2.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07641.x"},{"key":"2026070411350950000_2025.09.20.677502v2.13","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2011.545347"},{"key":"2026070411350950000_2025.09.20.677502v2.14","first-page":"8941057","article-title":"Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization","volume":"2020","year":"2020","journal-title":"Oxid Med Cell Longev"},{"key":"2026070411350950000_2025.09.20.677502v2.15","doi-asserted-by":"crossref","unstructured":"Qin, X. et al. 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