The effects of locus coeruleus ablation on mouse brain volume and microstructure evaluated by high-field MRI

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.