High phenylalanine concentrations induce demyelination and microglial activation in mouse cerebellar organotypic slices.

ABSTRACT: Phenylketonuria (PKU) is an inborn error of metabolism. Mutations in the enzyme phenylalanine hydroxylase (PAH)-encoding gene lead to a decreased metabolism of the amino acid phenylalanine (Phe). The deficiency in PAH increases Phe levels in blood and brain. Accumulation of Phe can lead to delayed development, psychiatric problems and cognitive impairment. White matter (WM) damage is a neuropathological hallmark of PKU and can be seen even in early detected and treated PKU patients. The mechanisms linking high Phe concentrations to WM abnormalities remain unclear. We tested the effects of high Phe concentrations on myelin in three in vitro models of increasing complexity: two simple cell culture models and one model that preserves local brain tissue architecture, a cerebellar organo

SUBMITTER: Thau-Zuchman O 

PROVIDER: S-EPMC9559601 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature