Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER Trafficking.

ABSTRACT: Anesthetic agents have been implicated in the causation of neurological and cognitive deficits after surgery, the exacerbation of chronic neurodegenerative disease, and were recently reported to promote the onset of the neurologic respiratory disease Congenital Central Hypoventilation Syndrome (CCHS), related to misfolding of the transcription factor Phox2B. To study how anesthetic agents could affect neuronal function through alterations to protein folding, we created neuronal cell models emulating the graded disease severity of CCHS. We found that the gas anesthetic isoflurane and the opiate morphine potentiated aggregation and mislocalization of Phox2B variants, similar to that seen in CCHS, and observed transcript and protein level changes consistent with activation of the endoplasmic

SUBMITTER: Coghlan M 

PROVIDER: S-EPMC5869676 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature