2026-07-27 バージニア工科大学（Virginia Tech）
＜関連情報＞
- https://news.vt.edu/articles/2026/07/research-fralinbiomed-roadblock.html
- https://journals.biologists.com/dmm/article/doi/10.1242/dmm.052786/372016/An-antioxidant-therapy-elicits-distinct
抗酸化療法は、22q11欠失上層皮質投射ニューロンにおいて特異的なトランスクリプトーム応答を引き起こす
An antioxidant therapy elicits distinct transcriptome responses in 22q11-deleted upper layer cortical projection neurons
Shah Rukh,Daniel W. Meechan,Abra Roberts,Connor Siggins,Zachary D. Erwin,Thomas M. Maynard,Anthony-S. LaMantia
Disease Models & Mechanisms Published:19 June 2026
DOI:https://doi.org/10.1242/dmm.052786
We characterized in vitro and in vivo responses to the antioxidant N-acetyl cysteine (NAC), which in the 22q11.2 Deletion Syndrome LgDel mouse model restores growth and connectivity of developing upper layer cortical projection neurons (Layer 2/3 PNs) and improves cognitive performance. NAC ameliorates L 2/3 PN developmental pathology without restoring wild type (WT) growth patterns or expression levels of downstream targets of 22q11-deleted genes. Instead, novel neuronal growth and antioxidant defense genes are differentially expressed compared to LgDel or WT: some generally NAC-regulated, others responsive only in the context of 22q11 deletion. NAC also elicits novel growth and antioxidant defense gene expression in differentiating 22q11-deleted L 2/3 PNs in postnatal LgDel mouse cortex rather than restoring 22q11 downstream targets to WT levels; however, these L 2/3 PN-selective in vivo changes differ substantially from those in primary culture. Thus, the NAC therapeutic response that diminishes oxidative stress-related L 2/3 PN developmental circuit and behavioral pathology due to 22q11 deletion has a distinct in vivo signature.
