Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice

Zinc is important in neural and synaptic development and neuronal transmission. Within the brain, zinc transporter 3 (ZnT3) is essential for zinc uptake into vesicles. Loss of vesicular zinc has been shown to produce neurodevelopmental disorder (NDD)-like behavior, such as decreased social interacti...

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Main Authors: Katy Celina Sandoval, Sarah E. Thackray, Alison Wong, Nicole Niewinski, Colten Chipak, Suhkjinder Rehal, Richard H. Dyck
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Behavioral Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnbeh.2022.769322/full
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author Katy Celina Sandoval
Katy Celina Sandoval
Katy Celina Sandoval
Sarah E. Thackray
Sarah E. Thackray
Sarah E. Thackray
Alison Wong
Alison Wong
Alison Wong
Nicole Niewinski
Nicole Niewinski
Nicole Niewinski
Colten Chipak
Colten Chipak
Colten Chipak
Suhkjinder Rehal
Suhkjinder Rehal
Suhkjinder Rehal
Richard H. Dyck
Richard H. Dyck
Richard H. Dyck
Richard H. Dyck
author_facet Katy Celina Sandoval
Katy Celina Sandoval
Katy Celina Sandoval
Sarah E. Thackray
Sarah E. Thackray
Sarah E. Thackray
Alison Wong
Alison Wong
Alison Wong
Nicole Niewinski
Nicole Niewinski
Nicole Niewinski
Colten Chipak
Colten Chipak
Colten Chipak
Suhkjinder Rehal
Suhkjinder Rehal
Suhkjinder Rehal
Richard H. Dyck
Richard H. Dyck
Richard H. Dyck
Richard H. Dyck
author_sort Katy Celina Sandoval
collection DOAJ
description Zinc is important in neural and synaptic development and neuronal transmission. Within the brain, zinc transporter 3 (ZnT3) is essential for zinc uptake into vesicles. Loss of vesicular zinc has been shown to produce neurodevelopmental disorder (NDD)-like behavior, such as decreased social interaction and increased anxiety- and repetitive-like behavior. Maternal immune activation (MIA) has been identified as an environmental factor for NDDs, such as autism spectrum disorders (ASDs) and schizophrenia (SZ), in offspring, which occurs during pregnancy when the mother’s immune system reacts to the exposure to viruses or infectious diseases. In this study, we investigated the interaction effect of a genetic factor [ZnT3 knockout (KO) mice] and an environmental factor (MIA). We induced MIA in pregnant female (dams) mice during mid-gestation, using polyinosinic:polycytidylic acid (polyI:C), which mimics a viral infection. Male and female ZnT3 KO and wild-type (WT) offspring were tested in five behavioral paradigms: Ultrasonic Vocalizations (USVs) at postnatal day 9 (P9), Open Field Test, Marble Burying Test, three-Chamber Social Test, and Pre-pulse Inhibition (PPI) in adulthood (P60–75). Our results indicate that loss of vesicular zinc does not result in enhanced ASD- and SZ-like phenotype compared to WT, nor does it show a more pronounced phenotype in male ZnT3 KO compared to female ZnT3 KO. Finally, MIA offspring demonstrated an ASD- and SZ-like phenotype only in specific behavioral tests: increased calls emitted in USVs and fewer marbles buried. Our results suggest that there is no interaction between the loss of vesicular zinc and MIA induction in the susceptibility to developing an ASD- and SZ-like phenotype.
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spelling doaj.art-c0eba5fba82b40e8b901336341553d6d2022-12-21T17:24:34ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532022-02-011610.3389/fnbeh.2022.769322769322Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation MiceKaty Celina Sandoval0Katy Celina Sandoval1Katy Celina Sandoval2Sarah E. Thackray3Sarah E. Thackray4Sarah E. Thackray5Alison Wong6Alison Wong7Alison Wong8Nicole Niewinski9Nicole Niewinski10Nicole Niewinski11Colten Chipak12Colten Chipak13Colten Chipak14Suhkjinder Rehal15Suhkjinder Rehal16Suhkjinder Rehal17Richard H. Dyck18Richard H. Dyck19Richard H. Dyck20Richard H. Dyck21Department of Psychology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute (HBI), University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, CanadaDepartment of Psychology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute (HBI), University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, CanadaDepartment of Psychology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute (HBI), University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, CanadaDepartment of Psychology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute (HBI), University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, CanadaDepartment of Psychology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute (HBI), University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, CanadaDepartment of Psychology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute (HBI), University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, CanadaDepartment of Psychology, University of Calgary, Calgary, AB, CanadaHotchkiss Brain Institute (HBI), University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, CanadaDepartment of Cell Biology and Anatomy, University of Calgary, Calgary, AB, CanadaZinc is important in neural and synaptic development and neuronal transmission. Within the brain, zinc transporter 3 (ZnT3) is essential for zinc uptake into vesicles. Loss of vesicular zinc has been shown to produce neurodevelopmental disorder (NDD)-like behavior, such as decreased social interaction and increased anxiety- and repetitive-like behavior. Maternal immune activation (MIA) has been identified as an environmental factor for NDDs, such as autism spectrum disorders (ASDs) and schizophrenia (SZ), in offspring, which occurs during pregnancy when the mother’s immune system reacts to the exposure to viruses or infectious diseases. In this study, we investigated the interaction effect of a genetic factor [ZnT3 knockout (KO) mice] and an environmental factor (MIA). We induced MIA in pregnant female (dams) mice during mid-gestation, using polyinosinic:polycytidylic acid (polyI:C), which mimics a viral infection. Male and female ZnT3 KO and wild-type (WT) offspring were tested in five behavioral paradigms: Ultrasonic Vocalizations (USVs) at postnatal day 9 (P9), Open Field Test, Marble Burying Test, three-Chamber Social Test, and Pre-pulse Inhibition (PPI) in adulthood (P60–75). Our results indicate that loss of vesicular zinc does not result in enhanced ASD- and SZ-like phenotype compared to WT, nor does it show a more pronounced phenotype in male ZnT3 KO compared to female ZnT3 KO. Finally, MIA offspring demonstrated an ASD- and SZ-like phenotype only in specific behavioral tests: increased calls emitted in USVs and fewer marbles buried. Our results suggest that there is no interaction between the loss of vesicular zinc and MIA induction in the susceptibility to developing an ASD- and SZ-like phenotype.https://www.frontiersin.org/articles/10.3389/fnbeh.2022.769322/fullvesicular zincmaternal immune activationautism spectrum disordersschizophreniapolyI:Cbehavior
spellingShingle Katy Celina Sandoval
Katy Celina Sandoval
Katy Celina Sandoval
Sarah E. Thackray
Sarah E. Thackray
Sarah E. Thackray
Alison Wong
Alison Wong
Alison Wong
Nicole Niewinski
Nicole Niewinski
Nicole Niewinski
Colten Chipak
Colten Chipak
Colten Chipak
Suhkjinder Rehal
Suhkjinder Rehal
Suhkjinder Rehal
Richard H. Dyck
Richard H. Dyck
Richard H. Dyck
Richard H. Dyck
Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice
Frontiers in Behavioral Neuroscience
vesicular zinc
maternal immune activation
autism spectrum disorders
schizophrenia
polyI:C
behavior
title Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice
title_full Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice
title_fullStr Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice
title_full_unstemmed Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice
title_short Lack of Vesicular Zinc Does Not Affect the Behavioral Phenotype of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation Mice
title_sort lack of vesicular zinc does not affect the behavioral phenotype of polyinosinic polycytidylic acid induced maternal immune activation mice
topic vesicular zinc
maternal immune activation
autism spectrum disorders
schizophrenia
polyI:C
behavior
url https://www.frontiersin.org/articles/10.3389/fnbeh.2022.769322/full
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