Early postnatal serotonin modulation prevents adult-stage deficits in Arid1b-deficient mice through synaptic transcriptional reprogramming

Hyosang Kim, Doyoun Kim, Yisul Cho, Kyungdeok Kim, Junyeop Daniel Roh, Yangsik Kim, Esther Yang, Seong Soon Kim, Sunjoo Ahn, Hyun Kim, Hyojin Kang, Yongchul Bae () and Eunjoon Kim ()
Additional contact information
Hyosang Kim: Korea Advanced Institute for Science and Technology (KAIST)
Doyoun Kim: Institute for Basic Science (IBS)
Yisul Cho: Kyungpook National University
Kyungdeok Kim: Institute for Basic Science (IBS)
Junyeop Daniel Roh: Institute for Basic Science (IBS)
Yangsik Kim: Korea Advanced Institute for Science and Technology (KAIST)
Esther Yang: Korea University
Seong Soon Kim: Korea Research Institute of Chemical Technology (KRICT)
Sunjoo Ahn: Korea Research Institute of Chemical Technology (KRICT)
Hyun Kim: Korea University
Hyojin Kang: Korea Institute of Science and Technology Information
Yongchul Bae: Kyungpook National University
Eunjoon Kim: Korea Advanced Institute for Science and Technology (KAIST)

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Autism spectrum disorder is characterized by early postnatal symptoms, although little is known about the mechanistic deviations that produce them and whether correcting them has long-lasting preventive effects on adult-stage deficits. ARID1B, a chromatin remodeler implicated in neurodevelopmental disorders, including autism spectrum disorder, exhibits strong embryonic- and early postnatal-stage expression. We report here that Arid1b-happloinsufficient (Arid1b+/–) mice display autistic-like behaviors at juvenile and adult stages accompanied by persistent decreases in excitatory synaptic density and transmission. Chronic treatment of Arid1b+/– mice with fluoxetine, a selective serotonin-reuptake inhibitor, during the first three postnatal weeks prevents synaptic and behavioral deficits in adults. Mechanistically, these rescues accompany transcriptomic changes, including upregulation of FMRP targets and normalization of HDAC4/MEF2A-related transcriptional regulation of the synaptic proteins, SynGAP1 and Arc. These results suggest that chronic modulation of serotonergic receptors during critical early postnatal periods prevents synaptic and behavioral deficits in adult Arid1b+/– mice through transcriptional reprogramming.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-32748-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32748-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-32748-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().