Maternal sevoflurane exposure disrupts oligodendrocyte myelination of the postnatal hippocampus and induces cognitive and motor impairments in offspring.

ABSTRACT

Maternal exposure to anesthetic agents could impose significant neurocognitive risks on the developing brain of infants. Myelin produced by oligodendrocytes (OLs) is essential for the development of brain. However, the concrete effect of general anesthesia on the development and myelination of OLs is still elusive. In this study, we aim to investigate postnatal myelination and neural behavior after maternal exposure to sevoflurane. Pregnant C57BL/6 J mice (gestational day 15.5) were anesthetized with 2.5% sevoflurane (in 97.5% O2) for 6 h. Cognitive function and motor coordination of the offspring mice were evaluated with novel object recognition, Morris water maze and accelerating rotarod tests. Myelination and development of hippocampal OLs were analyzed with immunohistochemistry, qRT-PCR, western blotting and electron microscopy. The functionality of myelin was measured with electrophysiology. Our results showed that sevoflurane anesthesia during the gestational period induced cognitive and motor impairments in offspring mice, accompanied with damages of myelin structure and down regulations of myelin-associated genes and proteins (including MBP, Olig1, PDGFRα, Sox10, etc.). The development and maturation of OLs were suppressed, and the axonal conduction velocity was declined. These results demonstrated that maternal sevoflurane exposure could induce detrimental effects on cognitive and motor functions in offspring, which might be associated with disrupted myelination of OLs in the hippocampus.