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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TitleLongitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism.
Publication TypeJournal Article
Year of Publication2012
AuthorsKumar, M, Kim, S, Pickup, S, Chen, R, Fairless, AH, Ittyerah, R, Abel, T, Brodkin, ES, Poptani, H
JournalBrain Res
Volume1455
Pagination56-67
Date Published2012 May 21
ISSN1872-6240
KeywordsAnimals, Autistic Disorder, Brain, Diffusion Tensor Imaging, Disease Models, Animal, Longitudinal Studies, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Neurologic Mutants, Social Behavior Disorders, Species Specificity
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 70 days-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 30 days-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.

DOI10.1016/j.brainres.2012.03.041
Alternate JournalBrain Res.
PubMed ID22513103
PubMed Central IDPMC3340503
Grant ListR21HD058237 / HD / NICHD NIH HHS / United States
UL1 RR024134-01 / RR / NCRR NIH HHS / United States
R01 MH080718 / MH / NIMH NIH HHS / United States
R21 HD058237-01A2 / HD / NICHD NIH HHS / United States
R01 MH080718-05 / MH / NIMH NIH HHS / United States
UL1RR024134 / RR / NCRR NIH HHS / United States
R01MH080718 / MH / NIMH NIH HHS / United States
R21 HD058237 / HD / NICHD NIH HHS / United States
UL1 RR024134 / RR / NCRR NIH HHS / United States
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