Distinct cellular and transcriptional mechanisms mediate an antioxidant therapeutic response in 22q11-deleted upper layer cortical projection neurons.

ABSTRACT: We characterized cellular and molecular mechanisms underlying the therapeutic response in vitro and in vivo to the antioxidant N-acetyl cysteine (NAC), which in the LgDel 22q11.2 Deletion Syndrome mouse model restores growth and connectivity of upper layer cortical projection neurons (Layer 2/3 PNs) and improves cognitive performance. NAC treatment of primary cultured LgDel L 2/3 PNs does not restore these neurons to a wild type (WT) state. Rather than returning to the bimodal dendrite and axon size distribution seen in WT, LgDel L 2/3 PN dendrite and axon growth in vitro increases unimodally in response to NAC. In parallel, altered expression of 22q11-deleted genes and presumed downstream targets are unchanged. Instead, novel antioxidant defense a

SUBMITTER: Rukh S 

PROVIDER: S-EPMC12710829 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature