Metoprolol Inhibits Developmental Brain Sterol Biosynthesis in Mice

Luke B. Allen, Károly Mirnics

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

De novo sterol synthesis is a critical homeostatic mechanism in the brain that begins during early embryonic development and continues throughout life. Multiple medications have sterol-biosynthesis-inhibiting side effects, with potentially detrimental effects on brain health. Using LC-MS/MS, we investigated the effects of six commonly used beta-blockers on brain sterol biosynthesis in vitro using cell lines. Two beta-blockers, metoprolol (MTP) and nebivolol, showed extreme elevations of the highly oxidizable cholesterol precursor 7-dehydrocholesterol (7-DHC) in vitro across multiple cell lines. We followed up on the MTP findings using a maternal exposure model in mice. We found that 7-DHC was significantly elevated in all maternal brain regions analyzed as well as in the heart, liver and brain of the maternally exposed offspring. Since DHCR7-inhibiting/7-DHC elevating compounds can be considered teratogens, these findings suggest that MTP utilization during pregnancy might be detrimental for the development of offspring, and alternative beta-blockers should be considered.

Original languageEnglish (US)
Article number1211
JournalBiomolecules
Volume12
Issue number9
DOIs
StatePublished - Sep 2022

Keywords

  • 7-DHC
  • DHCR7
  • LC-MS/MS
  • astrocyte
  • atenolol
  • beta-blockers
  • cell culture
  • cholesterol
  • desmosterol
  • nebivolol
  • neuron
  • propranolol

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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