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Neuroanatomical changes in a mouse model of early life neglect

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Abstract

Using a novel mouse model of early life neglect and abuse (ENA) based on maternal separation with early weaning, George et al. (BMC Neurosci 11:123, 2010) demonstrated behavioral abnormalities in adult mice, and Bordner et al. (Front Psychiatry 2(18):1–18, 2011) described concomitant changes in mRNA and protein expression. Using the same model, here we report neuroanatomical changes that include smaller brain size and abnormal inter-hemispheric asymmetry, decreases in cortical thickness, abnormalities in subcortical structures, and white matter disorganization and atrophy most severely affecting the left hemisphere. Because of the similarities between the neuroanatomical changes observed in our mouse model and those described in human survivors of ENA, this novel animal model is potentially useful for studies of human ENA too costly or cumbersome to be carried out in primates. Moreover, our current knowledge of the mouse genome makes this model particularly suited for targeted anatomical, molecular, and pharmacological experimentation not yet possible in other species.

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Acknowledgments

This work was supported by NIDA grant DA022251, a pilot grant from the Yale Center for Translational Study of Alcoholism (NIAAA grant P50 AA A06377), a grant from the Yale Center for Genomics to AS, and a grant from the Conway family (to AS). EG and KB were supported by NIMH grant T32-MH14276. KB and BC were supported by NIA Services grant P01 AG 030004-01A1. AS was supported by NCRR grant RR024138 and NIA grant AG030970 and a grant from the Yale Pepper Center. AD was supported by NIH grant 2 R01 NS014841-31. The DTI work and DC were supported by grant P30 NS052519 of the QNMR Program (to FH). The authors wish to thank Jane Taylor, Shannon Gourley, and Joan Kaufman for helpful discussions, Kiran D. Patel for skillful assistance and Dr. Michael Schwartz for allowing use of his Stereo Investigator hardware and software.

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Duque, A., Coman, D., Carlyle, B.C. et al. Neuroanatomical changes in a mouse model of early life neglect. Brain Struct Funct 217, 459–472 (2012). https://doi.org/10.1007/s00429-011-0350-9

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