Stress in Puberty Unmasks Latent Neuropathological Consequences of Prenatal Immune Activation in Mice
Double Whammy
Psychopathologies that cannot be explained by simple genetic or environmental circumstances may sometimes result from complex interplay between multiple inputs. Giovanoli et al. (p. 1095) analyzed the interactions between prenatal and postnatal stressors in mice to see what synergies give rise to psychopathologies in the adult mice. The results suggest that susceptibilities arise when mice are exposed to prenatal infection and also exposed to stressors around puberty. Stressors delivered later in adolescence did not seem to produce the same susceptibility. Although the mechanisms that impose the delay between stressors and psychopathology remain obscure, the timing and sequence of the triggers hint at possible cellular causes.
Abstract
Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry. We further demonstrate that the prenatal insult markedly increases the vulnerability of the pubescent offspring to brain immune changes in response to stress. Our findings reveal interactions between two adverse environmental factors that have individually been associated with neuropsychiatric disease and support theories that mental illnesses with delayed onsets involve multiple environmental hits.
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References and Notes
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Science
Volume 339 | Issue 6123
1 March 2013
1 March 2013
Copyright
Copyright © 2013, American Association for the Advancement of Science.
Submission history
Received: 1 August 2012
Accepted: 16 January 2013
Published in print: 1 March 2013
Acknowledgments
We thank L. Weber and T. Wirth for their technical assistance in the immunohistochemical and flow cytometric analyses; U. Stadlbauer and M. Labouesse for assisting behavioral experimentation and animal care; and the laboratory animal technician team, Schwerzenbach, for animal husbandry. We also thank W. Langhans for the continuous infrastructural support. This work was supported by the European Union Seventh Framework Programme (FP7/2007–2011) under Grant Agreement no. 259679 awarded to U.M.; by grants of the Swiss National Science Foundation (SNSF), ETH Zurich, and a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator grant awarded to J.F.; and by the Lundbeck Foundation, the Stanley Medical Research Institute, and a European Research Council Advanced Grant awarded to P.B.M.; and partially by the German Research Foundation (FOR 1581, SCHE 341/19-1; FOR 751, EN 814/1-2). All authors declare that they have no conflicts of interest to disclose. R.W. is employed by F. Hoffmann–La Roche, Ltd.
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