Effects of Developmental Arsenic Exposure on the Social Behavior and Related Gene Expression in C3H Adult Male Mice

Htway, Soe-Minn; Sein, Mya Thanda; Nohara, Keiko; Win-Shwe, Tin-Tin

doi:10.3390/ijerph16020174

Cited by 28 publications

(30 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently we have reported that developmental VPA and arsenic exposure impaired social behavior by modulating serotonin receptors and decreasing BDNF [28,43]. In the present study, we found downregulation of mRNA expression levels of social behavior related gene serotonin receptor 5HT5B and neurotrophic factors BDNF in the prefrontal cortex of male and female rats exposed to DE-SOA.…”

Section: Discussionsupporting

confidence: 68%

Perinatal exposure to diesel exhaust origin secondary organic aerosol induces autism-like behavior in rats

Shwe

Thu

Fujitani

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions and repetitive behaviors. The exact cause and mechanism of autism remains unknown. Both genetic and environmental factors may involve in ASD. In this study, we used diesel exhaust origin secondary organic aerosol (DE-SOA) as environmental pollutants. The aim of present study is to examine autism-like behaviors and related gene expressions in rats exposed to DE-SOA perinatally. Sprague-Dawley pregnant rats were exposed to clean air (control), diesel exhaust (DE) and DE-SOA in the exposure chamber for 5 h per day, 5days a week from gestational day 8 to postnatal day 21. At postnatal day 21, the male and female offspring rats were allocated into three different groups as follows: 1) rats exposed to clean filtered air; 2) rats exposed to DE; 3) rats exposed to DE-SOA. Social behaviors were investigated at 10~13-weeks-old rats using a 3-chambered social behavior test, social dominance tube test and marble burying test. Prefrontal cortex was collected under deep anesthesia to examine neurological and immunological markers, glutamate concentration, mast cell and microglia activation using real-time RT-PCR method, ELISA method and immunohistochemical analysis. Results: DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior and increased repetitive behavior compared with the control rats. The mRNA expression levels of serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) were down-regulated whereas interleukin 1 b　(IL-b), and heme oxygenase 1 (HO-1) were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA compared to the control rats. In addition, the expression of mast cells and microglia marker ionized calcium-binding adapter molecule (Iba)1 were increased in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was increased significantly in the prefrontal cortex of both male and female rats exposed to DE-SOA. Conclusion: Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior in rats by modulating neurological and immunological markers in the prefrontal cortex.

show abstract

Section: Discussionsupporting

confidence: 68%

Perinatal exposure to diesel exhaust origin secondary organic aerosol induces autism-like behavior in rats

Shwe

Thu

Fujitani

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Prenatal exposure to alcohol and arsenic has been shown to cause developmental neurotoxicity, affecting intellectual, emotional, and social functions permanently throughout later life [22,[24][25][26][27][28][29]. In the reporter transgenic mice, we observed RFP reporter expression, which reflects prior activation of HS signaling, in both neurons and glial cells broadly in the postnatal brain.…”

Section: Tracing the Lineage Of Cells Prenatally Affected By Environmmentioning

confidence: 77%

“…Arsenite is an inorganic form of arsenic, a metalloid naturally found in soil, air, and water in some zones of the world. Cumulative evidence from epidemiological and animal studies indicates that arsenic exposure in utero or in early childhood causes developmental neurotoxicity, affecting intellectual functions throughout life [24][25][26][27][28][29].…”

Section: Tracking Of the Cell Lineages Affected By Prenatal Exposure mentioning

confidence: 99%

Long-term spatial tracking of cells affected by environmental insults

Mohammad

Page

Sasaki

et al. 2020

J Neurodevelop Disord

View full text Add to dashboard Cite

Background Harsh environments surrounding fetuses and children can induce cellular damage in the developing brain, increasing the risk of intellectual disability and other neurodevelopmental disorders such as schizophrenia. However, the mechanisms by which early damage leads to disease manifestation in later life remain largely unknown. Previously, we demonstrated that the activation of heat shock (HS) signaling can be utilized as a unique reporter to label the cells that undergo specific molecular/cellular changes upon exposure to environmental insults throughout the body. Since the activation of HS signaling is an acute and transient event, this approach was not intended for long-term tracing of affected cells after the activation has diminished. In the present study, we generated new reporter transgenic mouse lines as a novel tool to achieve systemic and long-term tracking of affected cells and their progeny. Methods The reporter transgenic mouse system was designed so that the activation of HS signaling through HS response element (HSE) drives flippase (FLPo)-flippase recognition target (FRT) recombination-mediated permanent expression of the red fluorescent protein (RFP), tdTomato. With a priority on consistent and efficient assessment of the reporter system, we focused on intraperitoneal (i.p.) injection models of high-dose, short prenatal exposure to alcohol (ethanol) and sodium arsenite (ethanol at 4.0 g/kg/day and sodium arsenite at 5.0 mg/kg/day, at embryonic day (E) 12 and 13). Long-term reporter expression was examined in the brain of reporter mice that were prenatally exposed to these insults. Electrophysiological properties were compared between RFP+ and RFP− cortical neurons in animals prenatally exposed to arsenite. Results We detected RFP+ neurons and glia in the brains of postnatal mice that had been prenatally exposed to alcohol or sodium arsenite. In animals prenatally exposed to sodium arsenite, we also detected reduced excitability in RFP+ cortical neurons. Conclusion The reporter transgenic mice allowed us to trace the cells that once responded to prenatal environmental stress and the progeny derived from these cells long after the exposure in postnatal animals. Tracing of these cells indicates that the impact of prenatal exposure on neural progenitor cells can lead to functional abnormalities in their progeny cells in the postnatal brain. Further studies using more clinically relevant exposure models are warranted to explore this mechanism.

show abstract

“…In the present study, we found downregulation of mRNA expression levels of social behavior-related gene serotonin receptor 5HT5B and neurotrophic factor BDNF in the prefrontal cortex of male and female rats exposed to DE-SOA. Among serotonin receptors, 5HT5B was selected because this receptor is involved in social behavior [ 42 ]. BDNF is involved in synaptic plasticity which is critical for learning and memory functions.…”

Section: Discussionmentioning

confidence: 99%

Perinatal Exposure to Diesel Exhaust-Origin Secondary Organic Aerosol Induces Autism-Like Behavior in Rats

Win-Shwe

Kyi-Tha-Thu

Fujitani

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions, and repetitive behaviors. We aimed to examine autism-like behaviors and related gene expressions in rats exposed to diesel exhaust (DE)-origin secondary organic aerosol (DE-SOA) perinatally. Sprague–Dawley pregnant rats were exposed to clean air (control), DE, and DE-SOA in the exposure chamber from gestational day 14 to postnatal day 21. Behavioral phenotypes of ASD were investigated in 10~13-week-old offspring using a three-chambered social behavior test, social dominance tube test, and marble burying test. Prefrontal cortex was collected to examine molecular analyses including neurological and immunological markers and glutamate concentration, using RT-PCR and ELISA methods. DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior, and increased repetitive behavior. Serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) mRNAs were downregulated whereas interleukin 1 β (IL-β) and heme oxygenase 1 (HO-1) mRNAs were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was also increased significantly in DE-SOA-exposed male and female rats. Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior by modulating molecules such as neurological and immunological markers in rats.

show abstract

Effects of Developmental Arsenic Exposure on the Social Behavior and Related Gene Expression in C3H Adult Male Mice

Cited by 28 publications

References 50 publications

Perinatal exposure to diesel exhaust origin secondary organic aerosol induces autism-like behavior in rats

Perinatal exposure to diesel exhaust origin secondary organic aerosol induces autism-like behavior in rats

Long-term spatial tracking of cells affected by environmental insults

Perinatal Exposure to Diesel Exhaust-Origin Secondary Organic Aerosol Induces Autism-Like Behavior in Rats

Contact Info

Product

Resources

About