{"title":"镉抑制自由活动小鼠海马 CA1 神经元的钙活动","authors":"Megumi T Matsushita, Zhengui Xia","doi":"10.1093/toxsci/kfae048","DOIUrl":null,"url":null,"abstract":"Cadmium (Cd) is a ubiquitous toxic heavy metal and a potential neurotoxicant due to its wide use in industrial manufacturing processes and commercial products, including fertilizers. The general population is exposed to Cd through food and smoking due to high transfer rates of Cd from contaminated soil. Cd has been shown to mimic calcium ions (Ca2+) and interfere with intracellular Ca2+ levels and Ca2+ signaling in in vitro studies. However, nothing is known about Cd’s effects on Ca2+ activity in neurons in live animals. This study aimed to determine if Cd disrupts Ca2+ transients of neurons in CA1 region of the hippocampus during an associative learning paradigm. We utilized in vivo Ca2+ imaging in awake, freely moving C57BL/6 mice to measure Ca2+ activity in CA1 excitatory neurons expressing genetically encoded Ca2+ sensor GCaMP6 during an associative learning paradigm. We found that a smaller proportion of neurons are activated in Cd-treated groups compared to control during fear conditioning, suggesting that Cd may contribute to learning and memory deficit by reducing activity of neurons. We observed these effects at Cd exposure levels that result in blood Cd levels comparable to the general US population levels. This provides a possible molecular mechanism for Cd interference of learning and memory at exposure levels relevant to US adults. To our knowledge, our study is the first to describe Cd effects on brain Ca2+ activity in vivo in freely behaving mice.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cadmium inhibits calcium activity in hippocampal CA1 neurons of freely moving mice\",\"authors\":\"Megumi T Matsushita, Zhengui Xia\",\"doi\":\"10.1093/toxsci/kfae048\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Cadmium (Cd) is a ubiquitous toxic heavy metal and a potential neurotoxicant due to its wide use in industrial manufacturing processes and commercial products, including fertilizers. The general population is exposed to Cd through food and smoking due to high transfer rates of Cd from contaminated soil. Cd has been shown to mimic calcium ions (Ca2+) and interfere with intracellular Ca2+ levels and Ca2+ signaling in in vitro studies. However, nothing is known about Cd’s effects on Ca2+ activity in neurons in live animals. This study aimed to determine if Cd disrupts Ca2+ transients of neurons in CA1 region of the hippocampus during an associative learning paradigm. We utilized in vivo Ca2+ imaging in awake, freely moving C57BL/6 mice to measure Ca2+ activity in CA1 excitatory neurons expressing genetically encoded Ca2+ sensor GCaMP6 during an associative learning paradigm. We found that a smaller proportion of neurons are activated in Cd-treated groups compared to control during fear conditioning, suggesting that Cd may contribute to learning and memory deficit by reducing activity of neurons. We observed these effects at Cd exposure levels that result in blood Cd levels comparable to the general US population levels. This provides a possible molecular mechanism for Cd interference of learning and memory at exposure levels relevant to US adults. To our knowledge, our study is the first to describe Cd effects on brain Ca2+ activity in vivo in freely behaving mice.\",\"PeriodicalId\":23178,\"journal\":{\"name\":\"Toxicological Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-04-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicological Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/toxsci/kfae048\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicological Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/toxsci/kfae048","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Cadmium inhibits calcium activity in hippocampal CA1 neurons of freely moving mice
Cadmium (Cd) is a ubiquitous toxic heavy metal and a potential neurotoxicant due to its wide use in industrial manufacturing processes and commercial products, including fertilizers. The general population is exposed to Cd through food and smoking due to high transfer rates of Cd from contaminated soil. Cd has been shown to mimic calcium ions (Ca2+) and interfere with intracellular Ca2+ levels and Ca2+ signaling in in vitro studies. However, nothing is known about Cd’s effects on Ca2+ activity in neurons in live animals. This study aimed to determine if Cd disrupts Ca2+ transients of neurons in CA1 region of the hippocampus during an associative learning paradigm. We utilized in vivo Ca2+ imaging in awake, freely moving C57BL/6 mice to measure Ca2+ activity in CA1 excitatory neurons expressing genetically encoded Ca2+ sensor GCaMP6 during an associative learning paradigm. We found that a smaller proportion of neurons are activated in Cd-treated groups compared to control during fear conditioning, suggesting that Cd may contribute to learning and memory deficit by reducing activity of neurons. We observed these effects at Cd exposure levels that result in blood Cd levels comparable to the general US population levels. This provides a possible molecular mechanism for Cd interference of learning and memory at exposure levels relevant to US adults. To our knowledge, our study is the first to describe Cd effects on brain Ca2+ activity in vivo in freely behaving mice.
期刊介绍:
The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology.
The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field.
The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.