The effects of locus coeruleus ablation on mouse brain volume and
microstructure evaluated by high-field MRI
Abstract
Background and Purpose: The locus coeruleus (LC) produces the majority
of brain noradrenaline (NA). Among its many roles, NA has a protective
role for cells in the central nervous system. Loss of LC integrity is,
therefore, thought to cause alterations to brain volume and
microstructure, possibly driving the development of neurodegenerative
diseases. Experimental Approach: Ablation effect is ascertained by
behaviour analysis prior to ex vivo investigations. We use high-field
magnetic resonance imaging (MRI) to investigate brain volumetrics and
microstructure in control (CON) mice and mice with LC ablation (LCA) at
two ages. Our study employs whole-brain methods known to be capable of
detecting subtle morphological changes and brain microstructural
remodelling. Key Results: Mice show behaviour consistent with
histologically confirmed LC ablation. However, MRI shows no difference
between CON and LCA groups with regard to brain size, relative regional
volumes, or regional microstructural indices. Conclusion and
Implications: Our study suggests that LC-NA is not needed for postnatal
brain maturation and growth in mice. Nor is it required for maintenance
in the normal, adult mouse brain. This adds clarity to the
often-encountered notion that LC-NA is important for brain ”trophic
support” as it shows that such effects are likely most relevant to
mechanisms related to brain plasticity and neuroprotection.