{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:17Z","timestamp":1787029157827,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT)"},{"name":"Grants-in-Aid for Medical Scientific Research from the Japanese Ministry of Health, Labor and Welfare (MHLW)"},{"name":"Daiichi Sankyo Science Foundation (Daiichi Sankyo Company, Limited)"},{"name":"Takeda Science Foundation (Takeda Pharmaceutical Company, Limited)"},{"name":"Mitsubishi Tanabe Pharma Foundation (Mitsubishi Tanabe Pharma)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a central nervous system (CNS) neurodevelopmental disorder that includes autism, pervasive developmental disorder, and Asperger\u2019s syndrome. ASD is characterized by repetitive behaviors and social communication deficits. ASD is thought to be a multifactorial disorder with a range of genetic and environmental factors\/candidates. Among such factors is the rab2b gene, although it remains unclear how Rab2b itself is related to the CNS neuronal and glial developmental disorganization observed in ASD patients. Rab2 subfamily members regulate intracellular vesicle transport between the endoplasmic reticulum and the Golgi body. To the best of our knowledge, we are the first to report that Rab2b positively regulates neuronal and glial cell morphological differentiation. Knockdown of Rab2b inhibited morphological changes in N1E-115 cells, which are often used as the neuronal cell differentiation model. These changes were accomplished with decreased expression levels of marker proteins in neuronal cells. Similar results were obtained for FBD-102b cells, which are used as the model of oligodendroglial cell morphological differentiation. In contrast, knockdown of Rab2a, which is another Rab2 family member not known to be associated with ASD, affected only oligodendroglial and not neuronal morphological changes. In contrast, treatment with hesperetin, a citrus flavonoid with various cellular protective effects, in cells recovered the defective morphological changes induced by Rab2b knockdown. These results suggest that knockdown of Rab2b inhibits differentiation in neuronal and glial cells and may be associated with pathological cellular phenotypes in ASD and that hesperetin can recover their phenotypes at the in vitro level at least.<\/jats:p>","DOI":"10.3390\/neurolint15010025","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T03:35:42Z","timestamp":1678419342000},"page":"371-391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hesperetin Ameliorates Inhibition of Neuronal and Oligodendroglial Cell Differentiation Phenotypes Induced by Knockdown of Rab2b, an Autism Spectrum Disorder-Associated Gene Product"],"prefix":"10.3390","volume":"15","author":[{"given":"Yukino","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Molecular Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remina","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6756-3260","authenticated-orcid":false,"given":"Katsuya","family":"Ohbuchi","sequence":"additional","affiliation":[{"name":"Tsumura Research Laboratories, Tsumura & Co., Inashiki 200-1192, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Oizumi","sequence":"additional","affiliation":[{"name":"Tsumura Research Laboratories, Tsumura & Co., Inashiki 200-1192, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Tsumura Research Laboratories, Tsumura & Co., Inashiki 200-1192, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakana","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Pharmacognosy, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Mimaki","sequence":"additional","affiliation":[{"name":"Department of Medicinal Pharmacognosy, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-5799","authenticated-orcid":false,"given":"Yuki","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Tokyo, Japan"},{"name":"Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya 157-8535, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-998X","authenticated-orcid":false,"given":"Junji","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Tokyo, Japan"},{"name":"Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya 157-8535, Tokyo, Japan"},{"name":"Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Setagaya 156-8506, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4093","DOI":"10.1007\/s00018-012-1021-6","article-title":"Are Rab proteins the link between Golgi organization and membrane trafficking?","volume":"69","author":"Liu","year":"2012","journal-title":"Cell. 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