Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism

Manoj Kumar; Sungheon Kim; Stephen Pickup; Rong Chen; Andrew H Fairless; Ranjit Ittyerah; Ted Abel; Edward S Brodkin; Harish Poptani

doi:10.1016/j.brainres.2012.03.041

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Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism

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Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism

Manoj Kumar, Sungheon Kim, Stephen Pickup, Rong Chen, Andrew H Fairless, Ranjit Ittyerah, Ted Abel, Edward S Brodkin and Harish Poptani

Brain research, Vol.1455, pp.56-67

05/21/2012

DOI: 10.1016/j.brainres.2012.03.041

PMCID: PMC3340503

PMID: 22513103

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Abstract

Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders. ► BALB/cJ mice are less social at 30 days-of-age in comparison to B6 mice. ► Significant differences in fractional anisotropy of external capsule between BALB/cJ and B6 mice. ► Significant differences in developmental trajectories of FA from EC and FMC between BALB/cJ and B6 mice. ► Results indicate the potential of FA and MD as surrogate imaging markers for assessing brain under-connectivity.

Autism spectrum disorders

Fractional anisotropy

Mean diffusivity

Social behavior

Mouse models

Diffusion tensor imaging

Details

Title: Subtitle: Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism
Creators: Manoj Kumar - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA
Sungheon Kim - Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, 660 First Avenue, New York, NY, USA
Stephen Pickup - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA
Rong Chen - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA
Andrew H Fairless - Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Translational Research Laboratory, 125 South 31st Street, Philadelphia, PA 19104, USA
Ranjit Ittyerah - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA
Ted Abel - Department of Biology, University of Pennsylvania, 10–133 Translational Research Center, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USA
Edward S Brodkin - Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Translational Research Laboratory, 125 South 31st Street, Philadelphia, PA 19104, USA
Harish Poptani - Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, USA
Resource Type: Journal article
Publication Details: Brain research, Vol.1455, pp.56-67
DOI: 10.1016/j.brainres.2012.03.041
PMID: 22513103
PMCID: PMC3340503
NLM abbreviation: Brain Res
ISSN: 0006-8993
eISSN: 1872-6240
Publisher: Elsevier B.V
Grant note: name: NIH, award: R01MH080718, R21HD058237
Language: English
Date published: 05/21/2012
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065734502771

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