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Neuroimage. 2016 Jan 15;125:144-152. doi: 10.1016/j.neuroimage.2015.10.009. Epub 2015 Oct 14.

Morphological maturation of the mouse brain: An in vivo MRI and histology investigation.

Author information

1
Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstraße 50, Cologne, Germany. Electronic address: Luam.Mengler@sf.mpg.de.
2
Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstraße 50, Cologne, Germany; Croatian Institute for Brain Research, University of Zagreb School of Medicine, Šalata 12, Zagreb 10000, Croatia. Electronic address: sskokic@hiim.hr.
3
Division of Image Processing, Dept. of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; Percuros B.V., Drienerlolaan 5-Zuidhorst, 7522 Enschede, NB, The Netherlands. Electronic address: A.Khmelinskii@lumc.nl.
4
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Fahrstr. 17, 91054 Erlangen, Germany. Electronic address: andreas.hess@fau.de.
5
Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstraße 50, Cologne, Germany; Donders Institute for Brain, Cognition and Behaviour, Dept. of Cognitive Neuroscience, Radboud University Nijmegen, P.O. Box 9010, 6500 GL Nijmegen, The Netherlands. Electronic address: Noortje.vanderKnaap@radboudumc.nl.
6
Division of Image Processing, Dept. of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: M.Staring@lumc.nl.
7
Division of Image Processing, Dept. of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; Dept. of Intelligent Systems, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands. Electronic address: B.P.F.Lelieveldt@lumc.nl.
8
Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstraße 50, Cologne, Germany. Electronic address: dirk.wiedermann@sf.mpg.de.
9
Max Planck Institute for Metabolism Research, In-vivo-NMR Laboratory, Gleuelerstraße 50, Cologne, Germany; Division of Image Processing, Dept. of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; Percuros B.V., Drienerlolaan 5-Zuidhorst, 7522 Enschede, NB, The Netherlands. Electronic address: mathias@sf.mpg.de.

Abstract

With the wide access to studies of selected gene expressions in transgenic animals, mice have become the dominant species as cerebral disease models. 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-weighted MRI, 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.

KEYWORDS:

Brain development; Cortex; DTI; MRI; Mouse brain; Myelination

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