Repeated Exposure to Sevoflurane in Neonatal Mice Induces Cognitive and Synaptic Impairments in a TTLL6-Mediated Tubulin Polyglutamylation Manner.

ABSTRACT:

Aims

Repeated sevoflurane exposure during the neonatal stage may induce Tau phosphorylation, dendritic spine loss, and neurocognitive impairment in the developing brain. Tubulin tyrosine ligase like-6 (TTLL6), which aggregates in dendrites due to Tau missorting, regulates microtubule stability via α-tubulin polyglutamylation. Meanwhile, Spastin modulates dendritic spine formation by severing microtubules. We hypothesize that repeated sevoflurane treatment impairs dendritic spine remodeling in neonatal mice by enhancing TTLL6-mediated tubulin polyglutamylation and increasing Spastin expression, leading to cognitive dysfunction in their pre-adolescent stage.

Methods

Six-day-old wild type (WT), TTLL6 brain conditional knockout (TTLL6_CKO), TTLL6-flox (TTLL6_CON

SUBMITTER: Yu Y 

PROVIDER: S-EPMC11979716 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature