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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1498133

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

Provisionally accepted
Rasmus West Knopper Rasmus West Knopper 1,2*Christian Stald Skoven Christian Stald Skoven 1Simon Fristed Eskildsen Simon Fristed Eskildsen 1Leif Østergaard Leif Østergaard 1Brian Hansen Brian Hansen 1
  • 1 Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Capital Region of Denmark, Denmark
  • 2 University of Chinese Academy of Sciences, Sino Danish Centre for Education and Research (SDC), Beijing, China

The final, formatted version of the article will be published soon.

    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. For this, 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, representing the developing brain and the fully matured brain. Mice show behavior consistent with histologically confirmed LC ablation. The ablation effect is also ascertained using high-sensitivity ex vivo MRI. Our study employs whole-brain methods known to be capable of detecting subtle morphological changes and brain microstructural remodeling. However, MRI shows no difference between CON and LCA groups with regard to brain size, relative regional volumes, or regional microstructural indices. 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, 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.

    Keywords: Locus Coeruleus, DSP4, DKI, volumetrics, mouse brain, Behavior

    Received: 18 Sep 2024; Accepted: 28 Nov 2024.

    Copyright: © 2024 West Knopper, Skoven, Eskildsen, Østergaard and Hansen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rasmus West Knopper, Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, 8000, Capital Region of Denmark, Denmark

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.