TY - JOUR
T1 - Immunological stress at the maternal-foetal interface
T2 - A link between neurodevelopment and adult psychopathology
AU - Meyer, Urs
AU - Feldon, Joram
AU - Schedlowski, Manfred
AU - Yee, Benjamin K.
N1 - Funding Information:
The present study was supported by the Swiss Federal Institute of Technology Zurich, with additional support from the National Centre for Competence in Research: Neural Plasticity & Repair, Swiss National Science Foundation (J.F. and B.K.Y.). We are extremely grateful to Adrian Urwyler for running the cytokines assays, and to Peter Schmid and Misa Kuper-Yamanaka, respectively, for their technical and editorial assistance. We also remain indebted to Severin Schwendener for conducting the USPEE experiment, to Jeanne Michel and Pascal Guela for their care of the animals, and to Dr. Frank Bootz for his veterinary expertise.
PY - 2006/7
Y1 - 2006/7
N2 - Maternal infection during pregnancy is associated with a higher incidence of mental disorders, including schizophrenia, in the offspring in later life. Our recent attempt to study this link between prenatal immunological challenge and subsequent psychopathology has led to the establishment of a mouse model demonstrating the emergence of multiple psychotic-like phenotypes following immunological challenge on gestation day (GD) 9. However, little is known about the impact of similar in utero challenge at different times of pregnancy. Here, we compare the efficacy of identical maternal immune stimulation induced by the exposure to polyriboinosinic-polyribocytidilic acid (Poly(I:C)) at a dose of 5 mg/kg (i.v.) on distinct days of gestation (GD 6, 9, 13 or 17). The offspring derived were then compared to those collected from vehicle- and non-treated dams in two paradigms of selective associative learning: latent inhibition (LI) and the US-pre-exposure effect (USPEE). LI deficiency was observed in animals born to dams treated with Poly(I:C) on GD 6, 9 or 13, but not in those on GD17. In contrast, a loss of the USPEE was equivalently seen in all Poly(I:C) treatment groups, regardless of treatment times. Evaluation of the acute cytokine response in a separate cohort of pregnant dams receiving Poly(I:C) challenge on either GD9 or GD17 revealed that the ratio of interleukin-10/tumor necrosis factor-α was elevated in the GD17 relative to the GD9 group. The present report thus provides evidence that the acute cytokine reaction as well as the long-term pattern of behavioural sequelae of maternal immune challenge can be affected by its precise timing during pregnancy. The present study provides further support to the use of the prenatal Poly(I:C) model in the elucidation of mechanisms involved in the aetiology and disease process of immuno-precipitated neurodevelopmental mental diseases, including but not limited to, schizophrenia.
AB - Maternal infection during pregnancy is associated with a higher incidence of mental disorders, including schizophrenia, in the offspring in later life. Our recent attempt to study this link between prenatal immunological challenge and subsequent psychopathology has led to the establishment of a mouse model demonstrating the emergence of multiple psychotic-like phenotypes following immunological challenge on gestation day (GD) 9. However, little is known about the impact of similar in utero challenge at different times of pregnancy. Here, we compare the efficacy of identical maternal immune stimulation induced by the exposure to polyriboinosinic-polyribocytidilic acid (Poly(I:C)) at a dose of 5 mg/kg (i.v.) on distinct days of gestation (GD 6, 9, 13 or 17). The offspring derived were then compared to those collected from vehicle- and non-treated dams in two paradigms of selective associative learning: latent inhibition (LI) and the US-pre-exposure effect (USPEE). LI deficiency was observed in animals born to dams treated with Poly(I:C) on GD 6, 9 or 13, but not in those on GD17. In contrast, a loss of the USPEE was equivalently seen in all Poly(I:C) treatment groups, regardless of treatment times. Evaluation of the acute cytokine response in a separate cohort of pregnant dams receiving Poly(I:C) challenge on either GD9 or GD17 revealed that the ratio of interleukin-10/tumor necrosis factor-α was elevated in the GD17 relative to the GD9 group. The present report thus provides evidence that the acute cytokine reaction as well as the long-term pattern of behavioural sequelae of maternal immune challenge can be affected by its precise timing during pregnancy. The present study provides further support to the use of the prenatal Poly(I:C) model in the elucidation of mechanisms involved in the aetiology and disease process of immuno-precipitated neurodevelopmental mental diseases, including but not limited to, schizophrenia.
KW - Animal model
KW - Cytokines
KW - Latent inhibition
KW - Mouse
KW - Neurodevelopment
KW - Polyriboinosinic-polyribocytidilic acid
KW - Pregnancy
KW - Schizophrenia
KW - Selective attention
KW - US pre-exposure effect
UR - http://www.scopus.com/inward/record.url?scp=33646831799&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2005.11.003
DO - 10.1016/j.bbi.2005.11.003
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C2 - 16378711
AN - SCOPUS:33646831799
SN - 0889-1591
VL - 20
SP - 378
EP - 388
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
IS - 4
ER -