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The Journal of Neuroscience, May 3, 2006, 26(18):4752-4762; doi:10.1523/JNEUROSCI.0099-06.2006

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Behavioral/Systems/Cognitive
The Time of Prenatal Immune Challenge Determines the Specificity of Inflammation-Mediated Brain and Behavioral Pathology

Urs Meyer,^1 * Myriel Nyffeler,^1 * Andrea Engler,² Adrian Urwyler,² Manfred Schedlowski,² Irene Knuesel,¹ Benjamin K. Yee,¹ and Joram Feldon¹

¹Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, CH-8603 Schwerzenbach, Switzerland, and ²Laboratory of Psychology and Behavioural Immunobiology, Swiss Federal Institute of Technology Zurich, CH-8092 Zurich, Switzerland

Correspondence should be addressed to Dr. Benjamin K. Yee, Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland. Email: byee{at}ethz.ch

Disturbance to early brain development is implicated in several neuropsychiatric disorders including autism, schizophrenia, and mental retardation. Epidemiological studies have indicated that the risk of developing these disorders is enhanced by prenatal maternal infection, presumably as a result of neurodevelopmental defects triggered by cytokine-related inflammatory events. Here, we demonstrate that the effects of maternal immune challenge between middle and late gestation periods in mice are dissociable in terms of fetal brain cytokine responses to maternal inflammation and the pathological consequences in brain and behavior. Specifically, the relative expression of pro- and anti-inflammatory cytokines in the fetal brains in response to maternal immune challenge may be an important determinant among other developmental factors for the precise pathological profile emerging in later life. Thus, the middle and late gestation periods correspond to two windows with differing vulnerability to adult behavioral dysfunction, brain neuropathology in early adolescence, and of the acute cytokine responses in the fetal brain.

Key words: apoptosis; cytokines; inflammation; neurogenesis; prenatal; Reelin

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Received Jan. 10, 2006; revised March 16, 2006; accepted March 18, 2006.

Correspondence should be addressed to Dr. Benjamin K. Yee, Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland. Email: byee{at}ethz.ch

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Maternal Infection and the Offspring Brain

Amaicha Mara Depino
J. Neurosci. 2006 26: 7777-7778. [Full Text]  

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