Journal article

Substantially thinner internal granular layer and reduced molecular layer surface in the cerebellar cortex of the Tc1 mouse model of down syndrome - a comprehensive morphometric analysis with active staining contrast-enhanced MRI

Da Ma, Manuel J Cardoso, Maria A Zuluaga, Marc Modat, Nick M Powell, Frances K Wiseman, Jon O Cleary, Benjamin Sinclair, Ian F Harrison, Bernard Siow, Karteek Popuri, Sieun Lee, Joanne A Matsubara, Marinko Sarunic, Mirza Faisal Beg, Victor LJ Tybulewicz, Elizabeth MC Fisher, Mark F Lythgoe, Sebastien Ourselin

NeuroImage | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2020

Abstract

Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this ..

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University of Melbourne Researchers

Grants

Awarded by EPSRC


Awarded by UCL Leonard Wolfson Experimental Neurology cente


Awarded by Medical Research Council (MRC)


Awarded by EU-FP7 project VPHDARE@IT


Awarded by National Institute for Health Research University College London Hospitals Biomedical Research center (NIHR BRC UCLH/UCL High Impact Initiative)


Awarded by UK Regenerative Medicine Platform Safety Hub


Awarded by Wellcome Trust


Awarded by MRC


Awarded by Francis Crick Institute from the UK Medical Research Council


Awarded by Cancer Research UK


Funding Acknowledgements

This work received a proportion of funding from UCL Faculty of Engineering funding scheme. MJC receives funding from EPSRC (EP/H046410/1). MM is supported by the UCL Leonard Wolfson Experimental Neurology center (PR/ylr/18575). Funding received by NMP from the Medical Research Council MR/G09002073/1 (MRC, http://www.mrc.ac.uk/).SO receives funding from the EPSRC (EP/H046410/1, EP/J020990/1, EP/K005278), the MRC (MR/J01107X/1), the EU-FP7 project VPHDARE@IT (FP7-ICT-2011-9-601055), the NIHR Biomedical Research Unit (Dementia) at UCL and the National Institute for Health Research University College London Hospitals Biomedical Research center (NIHR BRC UCLH/UCL High Impact Initiative -BW.mn. BRC10269). ML receives funding from the Medical Research Council (MR/J013110/1), the UK Regenerative Medicine Platform Safety Hub (MRC: MR/K026739/1) (IRIS 104393) and the Kings College London and UCL Comprehensive Cancer Imaging center CR-UK & EPSRC (000012287) in association with the MRC and DoH (England). DM was partially funded by ASRP from Alzheimer Society Canada, MFB was funded by NSERC, CIHR, MSFHR Canada. IFH was supported by research grants from Eli Lilly and Company, and the EPSRC (EP/N034864/1). EMCF and VLJT were supported by grants from the Wellcome Trust (grant numbers 080174, 098327 and 098328). VLJT was also supported by MRC program U117527252 and by the Francis Crick Institute which receives its core funding from the UK Medical Research Council (FC001194), Cancer Research UK (FC001194) and the Wellcome Trust (FC001194). JOC is supported by a University of Melbourne McKenzie Fellowship.