Prenatal and postnatal maternal contributions in the infection model of schizophrenia.
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.
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, 8603, Schwerzenbach, Switzerland.
Urs
U
Meyer
Severin
S
Schwendener
Joram
J
Feldon
Benjamin K
BK
Yee
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005581:Foster Home Care; D007239:Infections / Q000150:complications* / Q000523:psychology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C; D011247:Pregnancy; D012559:Schizophrenia / Q000209:etiology*; D013649:Taste / Q000502:physiology
D011070:Poly I-C