T. gondii has also been linked to behavioral effects in nontarget hosts, including humans, where gender-specific effects on personality traits including self-control,

warmth, and novelty seeking (eg, tendency towards highrisk activities) have been observed.11-13 Many www.selleckchem.com/products/ZSTK474.html viruses affect behavior; for example, bornavirus (has been related to mania and schizoaffective disorders14-16); human immunodeficiency virus (linked to cognitive impairment, affective disorders, and psychosis17-19), rabies (a zoonotic infection caused by an enveloped single-stranded RNA virus that in its fulminant form is associated with hydrophobia20). The same is true of bacteria; cognitive Inhibitors,research,lifescience,medical and emotional disturbances have been associated with Brucella suis infection21; manic and psychotic symptoms resistant to antipsychotics but treatable with antibiotics during infection with Leptospira 22; baseline depression and anxiety caused by Mycobacterium tuberculosis 23; and obsessive-compulsive disorder (OCD) and pediatric autoimmune neuropsychiatric disorders associated with Inhibitors,research,lifescience,medical streptococcal Inhibitors,research,lifescience,medical infections (PANDAS).24,25 Poorly understood from a mechanistic perspective,

but perhaps more intriguing, are cases where an entire microbial community impacts host behavior. These effects have been noted when comparing the phenotypes of mice reared from birth and from generation to generation under sterile conditions in specialized gnotobiotic isolators that prevent any exposure to environmental microbes (“germ-free” animals) with mice that have been reared in Inhibitors,research,lifescience,medical the presence of microbes but under specified pathogen-free conditions (“conventionally raised” animals), or mice that were reared germ-free and then colonized at a given point in postnatal or adult life with a microbiota transplanted from a conventionally raised donor (so called “conventionalized” animals). For example, germ-free mice exhibit basal behaviors in the elevated plus maze (EPM) that are indicative of reduced anxiety levels.26 Using an implantable detector of locomotion for quantitative phenotyping, Backhed et al27 Inhibitors,research,lifescience,medical found that germ-free wild-type

(C57Bl/6J) mice have significantly increased movement compared with Endonuclease their microbe-laden counterparts, whether on a standard plant polysaccharide-rich, low-fat chow diet or a diet high in simple sugars and fat (Western diet). Conventionallyraised genetically engineered mice lacking Toll-like Receptor 5 (TLR5), a component of the innate immune system that recognizes bacterial flagellin, have an altered gut microbiota, eat substantially more than their conventionally-raised wild-type counterparts, and become obese. The same phenotype can be transmitted to germfree wild-type mice by transplanting a gut microbiota from a conventionally-raised TLR5 knockout donor,28 suggesting that it is the induced change in the microbiota that is changing the eating behavior.