Dataset Information

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.

SUBMITTER: Grabrucker S

PROVIDER: S-EPMC4776245 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Grabrucker Stefanie S Boeckers Tobias M TM Grabrucker Andreas M AM

Frontiers in behavioral neuroscience 20160303

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 Ne ...[more]

PMID: 26973485

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Project description:Recent literatures indicate that maternal hormone exposure is a risk factor for autism spectrum disorder (ASD). We hypothesize that prenatal progestin exposure may counteract the neuroprotective effect of estrogen and contribute to ASD development, and we aim to develop a method to ameliorate prenatal progestin exposure-induced autism-like behavior.Experiment 1: Prenatal progestin exposure-induced offspring are treated with resveratrol (RSV) through either prenatal or postnatal exposure and then used for autism-like behavior testing and other biomedical analyses. Experiment 2: Prenatal norethindrone (NET) exposure-induced offspring are treated with ER? knockdown lentivirus together with RSV for further testing. Experiment 3: Pregnant dams are treated with prenatal NET exposure together with RSV, and the offspring are used for further testing.Eight kinds of clinically relevant progestins were used for prenatal exposure in pregnant dams, and the offspring showed decreased ER? expression in the amygdala with autism-like behavior. Oral administration of either postnatal or prenatal RSV treatment significantly reversed this effect with ER? activation and ameliorated autism-like behavior. Further investigation showed that RSV activates ER? and its target genes by demethylation of DNA and histone on the ER? promoter, and then minimizes progestin-induced oxidative stress as well as the dysfunction of mitochondria and lipid metabolism in the brain, subsequently ameliorating autism-like behavior.We conclude that resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ER? activation. Our data suggest that prenatal progestin exposure is a strong risk factor for autism-like behavior. Many potential clinical progestin applications, including oral contraceptive pills, preterm birth drugs, and progestin-contaminated drinking water or seafood, may be risk factors for ASD. In addition, RSV may be a good candidate for clinically rescuing or preventing ASD symptoms in humans, while high doses of resveratrol used in the animals may be a potential limitation for human application.

Dataset Information

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

Publications

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

Similar Datasets

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