Longitudinal Diffusion Tensor Imaging Revealed Nerve Fiber Alterations in Aspm Mutated Microcephaly Model Mice. (10th February 2018)

• Record Type: Journal Article
• Authors: Ogi, Hiroshi; Nitta, Nobuhiro; Tando, So; Fujimori, Akira; Aoki, Ichio; Fushiki, Shinji; Itoh, Kyoko
• Is Part Of: Neuroscience. Volume 371(2018)
• Page Start: 325
• Page End: 336
• Publication Date: 2018-02-10
• Subjects: ac anterior commissure -- ASPM abnormal spindle-like, microcephaly-associated -- cc corpus callosum -- cg cingulum -- CNT control -- co cerebral cortex -- DTI diffusion tensor imaging -- ec external capsule -- FA fractional anisotropy -- hip hippocampus -- KO knockout -- LV lateral ventricle -- MBP myelin basic protein -- MCPH5 autosomal recessive primary microcephaly-5 -- RD radial diffusivity -- TBSS tract-based spatial statistics -- TFCE threshold-free cluster enhancement -- λ1 axial diffusivity; ASPM -- MCPH5 -- microcephaly -- in vivo MRI -- histopathology -- nerve fiber; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.12.012
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Postnatal brain development in Aspm KO mice was analyzed, using longitudinal in vivo MRI and histopathological analysis. The FA values were decreased in Aspm KO mice in both the cortex and white matter at postnatal 3 and 10 weeks. Histologically, the ratios of the horizontal to the vertical neurites were lower in the cortical layers in the KO mice. Spatiotemporal FA changes were coincident with histological neurite development in mice brain. Abnormal neurite differentiation underlie the mechanisms of the affected postnatal brain development in Aspm KO mice. Abstract: Autosomal recessive primary microcephaly-5 (MCPH5) is characterized by congenital microcephaly and is caused by the mutation in the abnormal spindle-like, microcephaly-associated ( ASPM ) gene. This study aimed to demonstrate a correlation between radiological and pathological analyses in evaluating postnatal brain development using MCPH5-model mice, ASPM ortholog ( Aspm ) knockout (KO) mice. In vivo MRI was performed at two time points (postnatal 3 weeks; P3W and P10W) and complementary histopathological analyses of brains were done at P5W and P13W. In the MRI analysis, Aspm KO mice showed significantly decreased brain sizes (average 8.6% difference) with larger ventricles (average 136.4% difference) at both time points. Voxel-based statistics showed that the fractional anisotropy (FA) values were significantly lower in Aspm KO mice in both the cortex and white matter at both time points. Developmental changes in the FA values were less remarkable in the Aspm KO mice, compared with the controls. Histometric analyses revealed that the ratios of the horizontal to the vertical neurites were significantly higher in cortical layers IV, V and VI, with a remarkable increase according to maturation at P13W in the control mice (average 12.7% difference between control and KO), whereas the ratio in layer VI decreased at P13W in the KO mice. The myelin basic protein positive ratio in the white matter significantly decreased in Aspm KO mice at P5W. These results suggest that temporal FA changes are closely correlated with pathological findings such as abnormal neurite outgrowth and differentiation, which may be applicable for analyzing diseased human brain development.