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

Abstract

The locus coeruleus (LC) produces most of the brain’s noradrenaline (NA). Among its many roles, NA is often said to be neuroprotective and important for brain upkeep. For this reason, loss of LC integrity is thought to impact brain volume and microstructure as well as plasticity broadly. LC dysfunction is also a suspected driver in the development of neurodegenerative diseases. Nevertheless, the impact of LC dysfunction on the gross structure and microstructure of normal brains is not well-studied. We employed high-field ex vivo magnetic resonance imaging (MRI) to investigate brain volumetrics and microstructure in control (CON) mice and mice with LC ablation (LCA) at two ages, representing the developing brain and the fully matured brain. These whole-brain methods are known to be capable of detecting subtle morphological changes and brain microstructural remodeling. We found mice behavior consistent with histologically confirmed LC ablation. However, MRI showed no difference between CON and LCA groups with regard to brain size, relative regional volumes, or regional microstructural indices. Our findings suggest 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, as no atrophy or microstructural aberration is detected after weeks of LC dysfunction. 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 in the (pre)diseased brain.