As we observed no GxE effects on these serological measures, one can suggest that these pathogenic antibodies might not be involved in the behavioral pathology exhibited by infected DN-DISC1 mice. for future mechanistic studies and evaluation of new treatments. 1. Introduction There has been a growing interest in the role of infectious agents in the development of Loviride psychiatric disorders. Epidemiological and immunological studies have identified microbial factors that may contribute to major psychiatric disorders, including schizophrenia and bipolar disorder [1, 2]. However, the mechanisms whereby microbes could affect the brain and behavior development remain incompletely understood. The consensus in the field is that both direct and indirect mechanisms could be at play to explain behavioral pathological changes observed in the infected host [3]. In order to advance our understanding of the mechanisms whereby microbes contribute to the pathophysiology of mental disease, most animal models have focused on indirect mechanisms that include the innate and/or adaptive immune responses to infectious agents [4, 5]. Assuming that most viral and/or bacterial pathogens activate similar immune signaling pathways, these studies have used synthetic immune stimulators to mimic viral (poly I?:?C) or bacterial (LPS) infection [6C8]. There have been generated very few animal models utilizing live pathogens. The major impediments for progress in generating appropriate animal models have been species-specific differences, increased mortality rate in rodents or the inability of a human virus or bacterium to replicate in the animal host without manipulating the microbe’s genome or the host’s immune system (e.g., HSV-1) [9]. In this context, (exposure (i.e., seropositivity) was associated with major psychiatric disorders [2, Loviride 10], including schizophrenia and bipolar disorder, we know very little why only a subset of seropositive subjects are diagnosed with a psychiatric disease. While genetic variability of the parasite’s genome and host’s age can modify behavioral pathology of the infected host [11C13], the role of the host’s genetic susceptibility remains practically unstudied. The only animal study has shown that deletion of a gene involved in dopamine synaptic neurotransmission, infection in mice [14]. No mouse model carrying a human psychiatric risk variant has been generated to evaluate possible gene-environment interaction (GxE) relevant to psychiatric disorders associated with exposure to is a gene disrupted by the Loviride balanced (1?:?11) (q42.1; q14.3) translocation, segregating in the Loviride Scottish family with several major psychiatric disorders, including schizophrenia, depression, and bipolar disorder [15C17]. Although the DISC1 locus has not been reported in the latest genome-wide association studies [18], rare mutations of large effects contribute to mental disorders [19] and are critical for uncovering the molecular pathobiology of psychiatric disease [20, 21]. It is in this context that we consider DISC1 as a major neurodevelopmental risk factor. The Scottish translocation may result in haplo-insufficiency or production of mutant DISC1 protein that could act in a dominant-negative manner [6, 16]. Both outcomes seem to lead to a similar disturbance in DISC1-interacting protein complexes and a loss of DISC1 function [6]. Thus, we use a C-terminus-truncated form of full-length protein as a dominant-negative molecular tool (DN-DISC1) to alter (i.e., decrease) expression of endogenous full-length DISC1 in order to elucidate the role of DISC1 in our mouse model of GxE. We found that chronic infection of DN-DISC1 mice led to an abnormal decrease in general locomotor activity and impaired prepulse inhibition of acoustic Loviride startle in a sex-dependent manner. The present study BCL1 describes a new mouse model of GxE to better our understanding of how exposure to could contribute to mental disease in human. 2. Methods and Materials 2.1. Animals Male and female BALB/c mice (the Jackson Laboratory, Bar Harbor, ME) were used in this study. Mice were housed 2C4 per cage (initially 5 per cage) in the.

As we observed no GxE effects on these serological measures, one can suggest that these pathogenic antibodies might not be involved in the behavioral pathology exhibited by infected DN-DISC1 mice