TY - JOUR
T1 - Prenatal and postnatal maternal contributions in the infection model of schizophrenia
AU - Meyer, Urs
AU - Schwendener, Severin
AU - Feldon, Joram
AU - Yee, Benjamin K.
N1 - Funding Information:
Acknowledgements 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 and Repair, Swiss National Science Foundation. We are extremely grateful to Peter Schmid for his technical assistance. We also remain indebted to Jeanne Michel and Pascal Guela for their care of the animals, and to Dr. Frank Bootz for his veterinary expertise.
PY - 2006/8
Y1 - 2006/8
N2 - Epidemiological studies have indicated that the risk of schizophrenia is enhanced by prenatal maternal infection with viral or bacterial pathogens. Recent experimentation in rodents has yielded additional support for a causal relationship between prenatal immune challenge and the emergence of psychosis-related abnormalities in brain and behaviour in later life. However, little is known about the putative roles of maternal postnatal factors in triggering and modulating the emergence of psychopathology following prenatal immunological stimulation. Here, we aimed to dissect the relative contributions of prenatal inflammatory events and postnatal maternal factors in precipitating juvenile and adult psychopathology in the resulting offspring with a cross-fostering design. Pregnant mice were exposed to the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 5 mg/kg, intravenously), or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were then simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. Prenatal PolyI:C administration did not affect the expression of latent inhibition (LI) at a juvenile stage of development, but led to the post-pubertal emergence of LI disruption in both aversive classical and instrumental conditioning regardless of the postnatal rearing condition. In addition, deficits in conditioning as such led to a pre- and post-pubertal loss of LI in prenatal control animals that were adopted by PolyI:C-treated surrogate mothers. Our findings thus indicate that the adoption of prenatally immune-challenged neonates by control surrogate mothers does not possess any protective effects against the subsequent emergence of psychopathology in adulthood. At the same time, however, the present study highlights for the first time that the adoption of prenatal control animals by immune-challenged rearing mothers is sufficient to precipitate learning disabilities in the juvenile and adult offspring.
AB - Epidemiological studies have indicated that the risk of schizophrenia is enhanced by prenatal maternal infection with viral or bacterial pathogens. Recent experimentation in rodents has yielded additional support for a causal relationship between prenatal immune challenge and the emergence of psychosis-related abnormalities in brain and behaviour in later life. However, little is known about the putative roles of maternal postnatal factors in triggering and modulating the emergence of psychopathology following prenatal immunological stimulation. Here, we aimed to dissect the relative contributions of prenatal inflammatory events and postnatal maternal factors in precipitating juvenile and adult psychopathology in the resulting offspring with a cross-fostering design. Pregnant mice were exposed to the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 5 mg/kg, intravenously), or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were then simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. Prenatal PolyI:C administration did not affect the expression of latent inhibition (LI) at a juvenile stage of development, but led to the post-pubertal emergence of LI disruption in both aversive classical and instrumental conditioning regardless of the postnatal rearing condition. In addition, deficits in conditioning as such led to a pre- and post-pubertal loss of LI in prenatal control animals that were adopted by PolyI:C-treated surrogate mothers. Our findings thus indicate that the adoption of prenatally immune-challenged neonates by control surrogate mothers does not possess any protective effects against the subsequent emergence of psychopathology in adulthood. At the same time, however, the present study highlights for the first time that the adoption of prenatal control animals by immune-challenged rearing mothers is sufficient to precipitate learning disabilities in the juvenile and adult offspring.
KW - Adoption
KW - Animal model
KW - Cytokines
KW - Infection
KW - Latent inhibition
KW - Learning
KW - PolyI:C
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=33747588330&partnerID=8YFLogxK
U2 - 10.1007/s00221-006-0419-5
DO - 10.1007/s00221-006-0419-5
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:33747588330
SN - 0014-4819
VL - 173
SP - 243
EP - 257
JO - Experimental Brain Research
JF - Experimental Brain Research
IS - 2
ER -