Available online 12 January 2024

Brain biometals change with age and are linked to several neurological diseases

Animal models of these disorders are commonly based on the C57BL/6 mouse

Brain iron, copper and zinc levels are regionally altered with age in C57BL/6 mouse

Formulae allow calculation of regional brain metal levels between 3-18 months of age

Comparison with human brain allows for improved study design and interpretation

Metal dyshomeostasis is associated with neurodegenerative disorders, cancers and vascular disease. We report the effects of age (range: 3 to 18 months) on regional copper, iron and zinc levels in the brain of the C57BL/6 mouse, a widely used inbred strain with a permissive background allowing maximal expression of mutations in models that recapitulate these disorders. We present formulae that can be used to determine regional brain metal concentrations in the C57BL/6 mouse at any age in the range of three to eighteen months of life. Copper levels in the C57BL/6 mouse adult brain were highest in the striatum and cerebellum and increased with age, excepting the cortex and hippocampus. Regional iron levels increased linearly with age in all brain regions, while regional zinc concentrations became more homogeneous with age. Knockdown of the copper transporter Ctr1 reduced brain copper, but not iron or zinc, concentrations in a regionally-dependent manner. These findings demonstrate biometals in the brain change with age in a regionally-dependent manner. These data and associated formulae have implications for improving design and interpretation of a wide variety of studies in the C57BL/6 mouse.

Copper

zinc

iron

aging

brain

C57/BL6 mouse

© 2024 The Author(s). Published by Elsevier Inc.