Maternal stress in Shank3ex4-9 mice increases pup-directed care and alters brain white matter in male offspring

Autoři: Bibiana K. Y. Wong aff001;  Jaclyn B. Murry aff003;  Rajesh Ramakrishnan aff001;  Fang He aff001;  Alfred Balasa aff004;  Gary R. Stinnett aff005;  Steen E. Pedersen aff005;  Robia G. Pautler aff005;  Ignatia B. Van den Veyver aff001
Působiště autorů: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, United States of America aff001;  Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas, United States of America aff002;  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America aff003;  Department of Pediatrics, Section of Pediatrics Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, Texas, United States of America aff004;  Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224876


Gene-environment interactions contribute to the risk for Autism Spectrum Disorder (ASD). Among environmental factors, prenatal exposure to stress may increase the risk for ASD. To examine if there is an interaction between exposure to maternal stress and reduced dosage or loss of Shank3, wild-type (WT), heterozygous (HET) and homozygous (HOM) female mice carrying a deletion of exons four through nine of Shank3 (Shank3ex4-9) were exposed to chronic unpredictable mild stress (CUMS) from prior to conception throughout gestation. This study examined maternal care of these dams and the white matter microstructure in the brains of their adult male offspring. Overall, our findings suggest that maternal exposure to CUMS increased pup-directed care for dams of all three genotypes. Compared to WT and HET dams, HOM dams also exhibited increased maternal care behaviors with increased time spent in the nest and reduced cage exploration, regardless of exposure to CUMS. Diffusion tensor imaging showed higher mean fractional anisotropy in the hippocampal stratum radiatum of WT and HOM male offspring from dams exposed to CUMS and HOM offspring from unexposed dams, compared to WT male offspring from unexposed dams. These data support that CUMS in Shank3-mutant dams results in subtle maternal care alterations and long-lasting changes in the white matter of the hippocampus of their offspring.

Klíčová slova:

Animal behavior – Autism spectrum disorder – Behavior – Central nervous system – Diffusion tensor imaging – Mice – Mouse models – Psychological stress


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