Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge.
Prenatal exposure to infections represents a risk factor for the emergence of neuropsychiatric disorders in later life, including schizophrenia and autism. However, it remains essentially unknown whether this association is primarily attributable to prenatal and/or postnatal maternal effects on the offspring. Here, we addressed this issue by dissecting the relative contributions of prenatal inflammatory events and postnatal maternal factors in an animal model of prenatal viral-like infection. Pregnant mice were exposed to the inflammatory agent polyriboinosinic-polyribocytidilic acid (PolyI:C; 5 mg/kg, i.v.) or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were cross fostered to surrogate rearing mothers that had either experienced inflammatory or sham treatment during pregnancy. We demonstrate that a variety of dopamine- and glutamate-related pharmacological and neuroanatomical disturbances emerge after prenatal immune challenge regardless of whether neonates were raised by vehicle- or PolyI:C-exposed surrogate mothers. However, the adoption of prenatal control animals to immune-challenged surrogate mothers was also sufficient to induce specific pharmacological and neuroanatomical abnormalities in the fostered offspring. Multiple schizophrenia-related dysfunctions emerging after prenatal immune challenge are thus mediated by prenatal but not postnatal maternal effects on the offspring, but immunological stress during pregnancy may affect postpartum maternal factors in such a way that being reared by an immune-challenged surrogate mother can confer risk for distinct forms of psychopathology in adult life.
Meyer
Urs
U
Laboratory of Behavioural Neurobiology, ETH Zurich, Schwerzenbach, Switzerland.
Nyffeler
Myriel
M
Schwendener
Severin
S
Knuesel
Irene
I
Yee
Benjamin K
BK
Feldon
Joram
J
D000578:Amidines / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005260:Female; D006185:Habituation, Psychophysiologic; D008297:Male; D008425:Maternal Behavior; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010332:Paternal Behavior; D011070:Poly I-C / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000523:psychology; D012559:Schizophrenia / Q000209:etiology* / Q000276:immunology; D012565:Schizophrenic Psychology
D000578:Amidines; C046728:2,2'-azobis(2-amidinopropane); D011070:Poly I-C