Characterization of pathological changes in the olfactory system of mice exposed to methylmercury
Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory...
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| Veröffentlicht in: | Archives of toxicology 2024-04, Vol.98 (4), p.1163-1175 |
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| creator | Iijima, Yuta Miki, Ryohei Takasugi, Nobumasa Fujimura, Masatake Uehara, Takashi |
| description | Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients. |
| doi_str_mv | 10.1007/s00204-024-03682-w |
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Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients.</description><identifier>ISSN: 0340-5761</identifier><identifier>ISSN: 1432-0738</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/s00204-024-03682-w</identifier><identifier>PMID: 38367039</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Apoptosis ; Astrocytes ; Biomedical and Life Sciences ; Biomedicine ; Cell death ; Correlation analysis ; cortex ; Cortex (olfactory) ; Cortex (somatosensory) ; Dimethylmercury ; Drinking water ; Environmental Health ; Humans ; Mercury ; Mercury (metal) ; mercury poisoning ; Mercury Poisoning, Nervous System ; Methylmercury ; methylmercury compounds ; Methylmercury Compounds - toxicity ; Mice ; Microglia ; Microglia - pathology ; Minamata disease ; nasal mucosa ; neurons ; neurotoxins ; Occupational Medicine/Industrial Medicine ; Odors ; Olfaction ; Olfaction Disorders - chemically induced ; Olfaction Disorders - complications ; Olfactory bulb ; olfactory disorders ; Olfactory epithelium ; Olfactory receptor neurons ; Organ Toxicity and Mechanisms ; Pharmacology/Toxicology ; prefrontal cortex ; Sensory evaluation ; Sensory neurons ; Toxicants</subject><ispartof>Archives of toxicology, 2024-04, Vol.98 (4), p.1163-1175</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Astrocytes</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell death</subject><subject>Correlation analysis</subject><subject>cortex</subject><subject>Cortex (olfactory)</subject><subject>Cortex (somatosensory)</subject><subject>Dimethylmercury</subject><subject>Drinking water</subject><subject>Environmental Health</subject><subject>Humans</subject><subject>Mercury</subject><subject>Mercury (metal)</subject><subject>mercury poisoning</subject><subject>Mercury Poisoning, Nervous System</subject><subject>Methylmercury</subject><subject>methylmercury compounds</subject><subject>Methylmercury Compounds - toxicity</subject><subject>Mice</subject><subject>Microglia</subject><subject>Microglia - pathology</subject><subject>Minamata disease</subject><subject>nasal mucosa</subject><subject>neurons</subject><subject>neurotoxins</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Odors</subject><subject>Olfaction</subject><subject>Olfaction Disorders - chemically induced</subject><subject>Olfaction Disorders - complications</subject><subject>Olfactory bulb</subject><subject>olfactory disorders</subject><subject>Olfactory epithelium</subject><subject>Olfactory receptor neurons</subject><subject>Organ Toxicity and Mechanisms</subject><subject>Pharmacology/Toxicology</subject><subject>prefrontal cortex</subject><subject>Sensory evaluation</subject><subject>Sensory neurons</subject><subject>Toxicants</subject><issn>0340-5761</issn><issn>1432-0738</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhD3BAlrj0Ejr-SOKcEFrxJVXqBc6W64w3rpJ4sR1K-PX1sqV8HOBgzWGeeW3PQ8hzBq8YQHueADjICng5olG8unlANkwKXkEr1EOyASGhqtuGnZAnKV0DMK468ZicCCWaFkS3IWY7mGhsxui_m-zDTIOje5OHMIadt2akdjDzDhP1M80D0jC6goe40rSmjNOBn7xFit_2IWFPc6AT5mEdJ4x2ietT8siZMeGzu3pKPr97-2n7obq4fP9x--aisrLucqWktApQOqucqRWrJSJyy3redLxHabF2wjjVQ19ze2Wga6QySoJABUY5cUpeH3P3y9WEvcU5RzPqffSTiasOxus_O7Mf9C581Qw6KaXoSsLZXUIMXxZMWU8-WRxHM2NYkhasFgqUZPBflHdccdk0bVPQl3-h12GJc1lFoepWFYfsQPEjZWNIKaK7fzgDfbCtj7Z1sa1_2NY3ZejF71--H_mptwDiCKTSKhbjr7v_EXsL6ye39Q</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Iijima, Yuta</creator><creator>Miki, Ryohei</creator><creator>Takasugi, Nobumasa</creator><creator>Fujimura, Masatake</creator><creator>Uehara, Takashi</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6562-2957</orcidid></search><sort><creationdate>20240401</creationdate><title>Characterization of pathological changes in the olfactory system of mice exposed to methylmercury</title><author>Iijima, Yuta ; Miki, Ryohei ; Takasugi, Nobumasa ; Fujimura, Masatake ; Uehara, Takashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-844c80e4fc8fa58154eee2c1d2692de4ce5f3af8d0d52cba09648a8403e80a8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Astrocytes</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell death</topic><topic>Correlation analysis</topic><topic>cortex</topic><topic>Cortex (olfactory)</topic><topic>Cortex (somatosensory)</topic><topic>Dimethylmercury</topic><topic>Drinking water</topic><topic>Environmental Health</topic><topic>Humans</topic><topic>Mercury</topic><topic>Mercury (metal)</topic><topic>mercury poisoning</topic><topic>Mercury Poisoning, Nervous System</topic><topic>Methylmercury</topic><topic>methylmercury compounds</topic><topic>Methylmercury Compounds - toxicity</topic><topic>Mice</topic><topic>Microglia</topic><topic>Microglia - pathology</topic><topic>Minamata disease</topic><topic>nasal mucosa</topic><topic>neurons</topic><topic>neurotoxins</topic><topic>Occupational Medicine/Industrial Medicine</topic><topic>Odors</topic><topic>Olfaction</topic><topic>Olfaction Disorders - chemically induced</topic><topic>Olfaction Disorders - complications</topic><topic>Olfactory bulb</topic><topic>olfactory disorders</topic><topic>Olfactory epithelium</topic><topic>Olfactory receptor neurons</topic><topic>Organ Toxicity and Mechanisms</topic><topic>Pharmacology/Toxicology</topic><topic>prefrontal cortex</topic><topic>Sensory evaluation</topic><topic>Sensory neurons</topic><topic>Toxicants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iijima, Yuta</creatorcontrib><creatorcontrib>Miki, Ryohei</creatorcontrib><creatorcontrib>Takasugi, Nobumasa</creatorcontrib><creatorcontrib>Fujimura, Masatake</creatorcontrib><creatorcontrib>Uehara, Takashi</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iijima, Yuta</au><au>Miki, Ryohei</au><au>Takasugi, Nobumasa</au><au>Fujimura, Masatake</au><au>Uehara, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of pathological changes in the olfactory system of mice exposed to methylmercury</atitle><jtitle>Archives of toxicology</jtitle><stitle>Arch Toxicol</stitle><addtitle>Arch Toxicol</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>98</volume><issue>4</issue><spage>1163</spage><epage>1175</epage><pages>1163-1175</pages><issn>0340-5761</issn><issn>1432-0738</issn><eissn>1432-0738</eissn><abstract>Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38367039</pmid><doi>10.1007/s00204-024-03682-w</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6562-2957</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis Astrocytes Biomedical and Life Sciences Biomedicine Cell death Correlation analysis cortex Cortex (olfactory) Cortex (somatosensory) Dimethylmercury Drinking water Environmental Health Humans Mercury Mercury (metal) mercury poisoning Mercury Poisoning, Nervous System Methylmercury methylmercury compounds Methylmercury Compounds - toxicity Mice Microglia Microglia - pathology Minamata disease nasal mucosa neurons neurotoxins Occupational Medicine/Industrial Medicine Odors Olfaction Olfaction Disorders - chemically induced Olfaction Disorders - complications Olfactory bulb olfactory disorders Olfactory epithelium Olfactory receptor neurons Organ Toxicity and Mechanisms Pharmacology/Toxicology prefrontal cortex Sensory evaluation Sensory neurons Toxicants |
| title | Characterization of pathological changes in the olfactory system of mice exposed to methylmercury |
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