Gender Dependent Evaluation of Autism like Behavior in Mice Exposed to Prenatal Zinc Deficiency

Abstract

Zinc deficiency has recently been linked to the etiology of autism spectrum disorders (ASD) as environmental risk factor. With an estimated 17% of the world population being at risk of zinc deficiency, especially zinc deficiency during pregnancy might be a common occurrence, also in industrialized nations. On molecular level, zinc deficiency has been shown to affect a signaling pathway at glutamatergic synapses that has previously been identified through genetic mutations in ASD patients, the Neurexin-Neuroligin-Shank pathway, via altering zinc binding Shank family members. In particular, prenatal zinc deficient but not acute zinc deficient animals have been reported to display autism like behavior in some behavioral tests. However, a full behavioral analysis of a possible autism like behavior has been lacking so far. Here, we performed an extensive behavioral phenotyping of mice born from mothers with mild zinc deficiency during all trimesters of pregnancy. Prenatal zinc deficient animals were investigated as adults and gender differences were assessed. Our results show that prenatal zinc deficient mice display increased anxiety, deficits in nest building and various social interaction paradigm, as well as mild alterations in ultrasonic vocalizations. A gender specific analysis revealed only few sex specific differences. Taken together, given that similar behavioral abnormalities as reported here are frequently observed in ASD mouse models, we conclude that prenatal zinc deficient animals even without specific genetic susceptibility for ASD, already show some features of ASD like behavior.

Effects of PM2.5 and gases exposure during prenatal and early-life on autism–like phenotypes in male rat offspring

“…3). The reduction in alternation in the Y-maze test also indicated restricted behavioral patterns (another core of ASD), in ALM, PGE, and GE rats [38].…”

Erroneous inference based on a lack of preference within one group: autism, mice, and the Social Approach Task

“…The Social Approach Task is one of the most widely utilized behavioral assays for investigation of mouse models of liability factors associated with autism spectrum disorders (ASD) (Bader et al, 2011; Chadman et al, 2008; Copping et al, 2017; Dougherty et al, 2013; Feyder et al, 2010; Grabrucker, Boeckers, & Grabrucker, 2016; Lugo, Swann, & Anderson, 2014; Maloney et al, 2018; Page, Kuti, Prestia, & Sur, 2009; Penagarikano et al, 2015; Samaco et al, 2012; Schwartzer et al, 2013; Stoppel et al, 2018; Won et al, 2012) The use of the Social Approach Task has both helped identify ASD liability models with good face validity, and advanced our understanding of the circuitry underlying social approach deficits. Unlike reciprocal social interaction assays requiring manual scoring, the Social Approach Task is automated, making it ideal for mechanistic studies that require several experiments with different interventions or genetic models.…”

Air pollutants reinforce autism–like behavior in the VPA-Induced – rat model of autism

“…Another way to demonstrate the repetitive behavior reported in VPA model, was the Y-maze test, a test designed to evaluate short-term, spatial memory [67]. However, the reduction of the Y-maze test could also indicate a restricted behavioral pattern, another core of ASD [65,68]. As shown in Fig.…”

“…The test was conducted as previously described by Grabrucker et al [68]. Spontaneous alternation behavior was assessed at PND57 for each rat in a symmetrical Y Maze (3 arms, 40*9 cm with 16 cm height of walls).…”