Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Abstract

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Immune–neural connections: how the immune system’s response to infectious agents influences behavior

“…These data suggest that other cytokines are necessary for the behavioral response, as discussed earlier in the IFN section. In addition to prolonged fatigue, prenatal exposure of dams to poly I:C has been used as a model for inflammation-induced schizophrenia-like behaviors that are expressed by the offspring (Macêdo et al, 2012;Piontkewitz et al, 2012). Thus, age-at-exposure to an immune challenge alters the phenotypic expression pattern.…”

Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression

“…The neurotrophic alterations observed in depression are mainly associated with decreased levels of brain-derived neurotrophic factor (BDNF). Indeed, this neurotrophin is regarded as an important biomarker to various psychiatric disorders such as depression (Schmidt et al, 2011;Melo et al, 2013), schizophrenia (Nieto et al, 2013;Vasconcelos et al, 2015;Macêdo et al, 2012aMacêdo et al, , 2012b, Alzheimer′s disease (Rosa and Fahnestock, 2014) and Parkinson's disease (Howells et al, 2000).…”

Maternal inflammation promotes fetal microglial activation and increased cholinergic expression in the fetal basal forebrain: role of interleukin-6

“…Recent papers describing possible genetic bases for autism spectrum disorder have been promising (1,2), but evidence also suggests that perinatal exposure to infectious agents with associated maternal and/or fetal immune activation may combine with a genetic predisposition to produce autism spectrum disorder and schizophrenia (3)(4)(5)(6)(7)(8). Animal studies confirm that maternal immune activation (MIA) leads to behavioral and morphological anomalies reminiscent of the disorder (9)(10)(11)(12)(13).…”