CYP1B1 affects the integrity of the blood-brain barrier and oxidative stress in the striatum: An investigation of manganese-induced neurotoxicity.

ABSTRACT:

Aims

Excessive influx of manganese (Mn) into the brain across the blood-brain barrier induces neurodegeneration. CYP1B1 is involved in the metabolism of arachidonic acid (AA) that affects vascular homeostasis. We aimed to investigate the effect of brain CYP1B1 on Mn-induced neurotoxicity.

Method

Brain Mn concentrations and α-synuclein accumulation were measured in wild-type and CYP1B1 knockout mice treated with MnCl₂ (30 mg/kg) and biotin (0.2 g/kg) for 21 continuous days. Tight junctions and oxidative stress were analyzed in hCMEC/D3 and SH-SY5Y cells after the treatment with MnCl₂ (200 μM) and CYP1B1-derived AA metabolites (HETEs and EETs).

Results

Mn exposure inhibited brain CYP1B1, and CYP1B1 deficiency increased brain Mn concentrations and a

SUBMITTER: Wu J 

PROVIDER: S-EPMC10907825 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature