Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia.
It has been hypothesized that the maternal immune response to infection may influence fetal brain development and lead to schizophrenia. Animal experimentation has supported this notion by demonstrating altered sensorimotor gating (prepulse inhibition, PPI) in adult rats prenatally exposed to an immune challenge. In the present study, pregnant rats were exposed to the bacterial endotoxin lipopolysaccharide (LPS) throughout gestation and the offspring were examined by evaluating the PPI, dopaminergic function, brain protein expression and cytokine serum levels from weaning to late adulthood. Prenatal LPS exposure induced a deficit in PPI that emerged at 'puberty' and that persisted throughout adult life. This prenatal insult caused age-specific changes in accumbal dopamine levels and in synaptophysin expression in the frontal cortex. Moreover, serum cytokine levels were altered in an age- and cytokine-dependent manner. Here we show that prenatal LPS administration throughout pregnancy causes maturation-dependent PPI deficits and age-dependent alterations in dopamine activity, as well as in synaptophysin expression and cytokine levels.
Romero
E
E
Group of Neuroimmunology, Functional and Systems Neurobiology Department, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid 28002, Spain.
Guaza
C
C
Castellano
B
B
Borrell
J
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003423:Critical Period, Psychological; D016207:Cytokines / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006719:Homovanillic Acid / Q000378:metabolism; D007154:Immune System Diseases / Q000209:etiology*; D008098:Litter Size / Q000276:immunology / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D011134:Polysaccharides / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology; D055139:Sensory Gating / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
D016207:Cytokines; D011134:Polysaccharides; D016708:Synaptophysin; D014404:Tubulin; D015102:3,4-Dihydroxyphenylacetic Acid; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D004298:Dopamine; D003345:Corticosterone; D006719:Homovanillic Acid