| RRC ID |
85977
|
| 著者 |
Tanabe M, Saito Y, Takasaki A, Nakano K, Yamamoto S, Suzuki C, Kawamura N, Hattori A, Oikawa M, Nagashima S, Yanagi S, Yamaguchi T, Fukuda T.
|
| タイトル |
Role of immature choroid plexus in the pathology of model mice and human iPSC-derived organoids with autism spectrum disorder.
|
| ジャーナル |
Cell Rep
|
| Abstract |
During gestation, the choroid plexus (ChP) produces protein-rich cerebrospinal fluid and matures prior to brain development. It is assumed that ChP dysfunction has a profound effect on developmental neuropsychiatric disorders, such as autism spectrum disorder (ASD). However, the mechanisms linking immature ChP to the onset of ASD remain unclear. Here, we find that ChP-specific CAMDI-knockout mice develop an immature ChP alongside decreased multiciliogenesis and expression of differentiation marker genes following disruption of the cerebrospinal fluid barrier. These mice exhibit ASD-like behaviors, including anxiety and impaired socialization. Additionally, the administration of metformin, an FDA-approved drug, before the social critical period achieves ChP maturation and restores social behaviors. Furthermore, both the ASD model mice and organoids derived from patients with ASD developed an immature ChP. These results propose the involvement of an immature ChP in the pathogenesis of ASD and suggest the targeting of functional maturation of the ChP as a therapeutic strategy for ASD.
|
| 巻・号 |
44(1)
|
| ページ |
115133
|
| 公開日 |
2025-1-28
|
| DOI |
10.1016/j.celrep.2024.115133
|
| PII |
S2211-1247(24)01484-0
|
| PMID |
39731733
|
| MeSH |
Animals
Autism Spectrum Disorder* / metabolism
Autism Spectrum Disorder* / pathology
Cell Differentiation
Choroid Plexus* / metabolism
Choroid Plexus* / pathology
Disease Models, Animal
Humans
Induced Pluripotent Stem Cells* / metabolism
Induced Pluripotent Stem Cells* / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Organoids* / metabolism
Organoids* / pathology
|
| IF |
8.109
|
| リソース情報 |
| ヒト・動物細胞 |
HPS2959
HPS2612
HPS2085 |
