TY - JOUR
T1 - The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology
AU - Meyer, Urs
AU - Nyffeler, Myriel
AU - Engler, Andrea
AU - Urwyler, Adrian
AU - Schedlowski, Manfred
AU - Knuesel, Irene
AU - Yee, Benjamin K.
AU - Feldon, Joram
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cytokines
KW - Inflammation
KW - Neurogenesis
KW - Prenatal
KW - Reelin
UR - http://www.scopus.com/inward/record.url?scp=33646926705&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0099-06.2006
DO - 10.1523/JNEUROSCI.0099-06.2006
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C2 - 16672647
AN - SCOPUS:33646926705
SN - 0270-6474
VL - 26
SP - 4752
EP - 4762
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 18
ER -