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Open AccessArticle

Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia

by 1,†, 1,†, 2 and 1,3,4,*
1
Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10048, Taiwan
2
National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli 35053, Taiwan
3
Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 10048, Taiwan
4
Neurobiology and Cognitive Science Center, National Taiwan University, Taipei 10617, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally in this study.
Int. J. Mol. Sci. 2020, 21(22), 8518; https://doi.org/10.3390/ijms21228518
Received: 26 October 2020 / Revised: 9 November 2020 / Accepted: 9 November 2020 / Published: 12 November 2020
Schizophrenia is a multifactorial developmental neuropsychiatric disorder. This study examined the interplay of maternal infection and postweaning social isolation, which are prenatal and postnatal risk factors, respectively. Pregnant mice received poly I:C or saline injection on gestation day 9 and the pups were weaned at postnatal day 28. After weaning, male offspring were randomly assigned into group-rearing and isolation-rearing groups. In their adulthood, we performed behavioral tests and characterized the histochemical features of their mesocorticolimbic structures. The sociability and anxiety levels were not affected by either manipulation, but synergistic effects of the two hits on stress-coping behavior was observed. Either of the single manipulations caused defects in sensorimotor gating, novel object recognition and spatial memory tests, but the combination of the two hits did not further exacerbate the disabilities. Prenatal infection increased the number of dopaminergic neurons in midbrain, whereas postweaning isolation decreased the GABAergic neurons in cortex. Single manipulation reduced the dendritic complexity and spine densities of neurons in the medial prefrontal cortex (mPFC) and dentate gyrus. Our results support the current perspective that disturbances in brain development during the prenatal or postnatal period influence the structure and function of the brain and together augment the susceptibility to mental disorders, such as schizophrenia. View Full-Text
Keywords: risk factors; schizophrenia; stress-coping; ventral tegmental area (VTA); mPFC; dendritic structure risk factors; schizophrenia; stress-coping; ventral tegmental area (VTA); mPFC; dendritic structure
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MDPI and ACS Style

Chang, Y.-C.; Li, W.-Y.; Lee, L.J.-H.; Lee, L.-J. Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia. Int. J. Mol. Sci. 2020, 21, 8518. https://doi.org/10.3390/ijms21228518

AMA Style

Chang Y-C, Li W-Y, Lee LJ-H, Lee L-J. Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia. International Journal of Molecular Sciences. 2020; 21(22):8518. https://doi.org/10.3390/ijms21228518

Chicago/Turabian Style

Chang, Yi-Chun; Li, Wai-Yu; Lee, Lukas J.-H.; Lee, Li-Jen. 2020. "Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia" Int. J. Mol. Sci. 21, no. 22: 8518. https://doi.org/10.3390/ijms21228518

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