Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics.
Increasing evidence suggests that pre- or perinatal events that influence the immune system contribute to the development of behavioral or neuropsychiatric disorders. For instance, exposure of pregnant rats to the bacterial endotoxin lipopolysaccharide (LPS) disrupts sensorimotor information processing, as assessed by the prepulse inhibition test (PPI), and also the immune function in adult offspring, which might be of particular relevance as regards schizophrenia. However, the consequences of maternal LPS exposure during pregnancy on synaptic functioning in adult offspring and, more importantly, the therapeutic opportunity to re-establish PPI and immune function have still to be demonstrated. In this work, we analyzed the consequences of prenatal LPS exposure on dopaminergic neurotransmission and presynaptic markers in adult brain areas related to PPI circuitry. In addition, we tested whether oral treatment with the typical antipsychotic drug haloperidol (HAL) could reinstate PPI performances and cytokine serum levels in six-month-old male rats with prenatal LPS exposure. Both sensory information processing deficits and immune anomalies induced by prenatal exposure to LPS were accompanied by changes in dopaminergic neurotransmission and synaptophysin expression. It is important to note that PPI disruption and serum increases in cytokines induced by prenatal LPS exposure were both reversed by HAL. Taken together, these results demonstrate the critical influence of prenatal immune events on the functioning of adult nervous and immune systems, in association with the putative role of the immune system in the development of behavior relevant to schizophrenia.
Romero
Eva
E
Cajal Institute, Spanish Council for Scientific Research (CSIC), Avda Doctor Arce, Madrid, Spain. Eva.Romero@ens-lyon.fr
Ali
Carine
C
Molina-Holgado
Eduardo
E
Castellano
Bernardo
B
Guaza
Carmen
C
Borrell
José
J
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage*; D007154:Immune System Diseases / Q000188:drug therapy* / Q000209:etiology; D007266:Inhibition, Psychological; D008070:Lipopolysaccharides; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012678:Sensation Disorders / Q000188:drug therapy* / Q000209:etiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D014150:Antipsychotic Agents; D016207:Cytokines; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D008070:Lipopolysaccharides; D006220:Haloperidol; D004298:Dopamine