Morphological maturation of the mouse brain
An in vivo MRI and histology investigation
Luam Hammelrath (Max Planck Institute for Metabolism Research)
Siniša Škokić (Max Planck Institute for Metabolism Research, University of Zagreb)
Artem Khmelinskii (Percuros B.V, Leiden University Medical Center)
Andreas Hess (Friedrich-Alexander-Universität Erlangen-Nürnberg)
Noortje van der Knaap (Radboud Universiteit Nijmegen, Max Planck Institute for Metabolism Research)
Marius Staring (Leiden University Medical Center)
Boudewijn Lelieveldt (TU Delft - Pattern Recognition and Bioinformatics, Leiden University Medical Center)
Dirk Wiedermann (Max Planck Institute for Metabolism Research)
Mathias Hoehn (Max Planck Institute for Metabolism Research, Percuros B.V, Leiden University Medical Center)
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Abstract
With the wide access to studies of selected gene expressions in transgenic animals,mice have become the dominant species as cerebral diseasemodels. Many of these studies are performed on animals of not more than eight weeks, declared as adult animals. Based on the earlier reports that full brain maturation requires at least three months in rats, there is a clear need to discern the corresponding minimal animal age to provide an “adult brain” in mice in order to avoid modulation of disease progression/therapy studies by ongoing developmental changes. For this purpose, we have studied anatomical brain alterations of mice during their first six months of age. Using T2-weighted and diffusion-weightedMRI, structural and volume changes of the brain were identified and compared with histological analysis of myelination. Mouse brain volume was found to be almost stable already at three weeks, but cortex thickness kept decreasing continuously with maximal changes during the first
three months. Myelination is still increasing between three and six months, although most dramatic changes are over by three months. While our results emphasize that mice should be at least three months old when adult animals are needed for brain studies, preferred choice of one particular metric for future investigation goals will result in somewhat varying age windows of stabilization.
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