Developmental exposure to mancozeb induced neurochemical and morphological alterations in adult male mouse hypothalamus
•Developmental exposure altered amino acid neurotransmission in adult hypothalamus.•Variations in glutamate and GABA levels showed increased excitation/inhibition ratio.•Morphological changes revealed mitochondrial edema and demyelination in hypothalamus. Mancozeb, a dithiocarbamate widely used in a...
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| Veröffentlicht in: | Environmental toxicology and pharmacology 2018-12, Vol.64, p.139-146 |
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| creator | Morales-Ovalles, Yasmin Miranda-Contreras, Leticia Peña-Contreras, Zulma Dávila-Vera, Delsy Balza-Quintero, Alirio Sánchez-Gil, Beluardi Mendoza-Briceño, Rosa Virginia |
| description | •Developmental exposure altered amino acid neurotransmission in adult hypothalamus.•Variations in glutamate and GABA levels showed increased excitation/inhibition ratio.•Morphological changes revealed mitochondrial edema and demyelination in hypothalamus.
Mancozeb, a dithiocarbamate widely used in agriculture, is considered a developmental hazard in humans; however, more evidences are still needed concerning the consequences of chronic exposure to this pesticide. Mancozeb neurotoxicity in developing mouse hypothalamus was evaluated by subchronic exposure of male Mus musculus mice to low and high doses of mancozeb (30 and 90 mg/kg body weight, respectively) from late neonatal until adolescence. Variations in hypothalamic amino acid neurotransmitter levels and changes in histological as well as cytological characteristics were analyzed in young adult experimental mice and compared with control. A dose-dependent increase in excitation/ inhibition ratio was observed in mancozeb-exposed hypothalamus, indicating an overall state of excitoxicity. Histopathological and ultrastructural studies showed increased apoptosis, neuroinflammation and demyelination, demonstrating mancozeb-induced cytotoxicity in hypothalamic neurosecretory cells. In summary, both neurochemical and morphological data revealed mancozeb-induced alterations during development of hypothalamic circuitry that are critical for maturation of the neuroendocrine system. |
| doi_str_mv | 10.1016/j.etap.2018.10.004 |
| format | Article |
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Mancozeb, a dithiocarbamate widely used in agriculture, is considered a developmental hazard in humans; however, more evidences are still needed concerning the consequences of chronic exposure to this pesticide. Mancozeb neurotoxicity in developing mouse hypothalamus was evaluated by subchronic exposure of male Mus musculus mice to low and high doses of mancozeb (30 and 90 mg/kg body weight, respectively) from late neonatal until adolescence. Variations in hypothalamic amino acid neurotransmitter levels and changes in histological as well as cytological characteristics were analyzed in young adult experimental mice and compared with control. A dose-dependent increase in excitation/ inhibition ratio was observed in mancozeb-exposed hypothalamus, indicating an overall state of excitoxicity. Histopathological and ultrastructural studies showed increased apoptosis, neuroinflammation and demyelination, demonstrating mancozeb-induced cytotoxicity in hypothalamic neurosecretory cells. In summary, both neurochemical and morphological data revealed mancozeb-induced alterations during development of hypothalamic circuitry that are critical for maturation of the neuroendocrine system.</description><identifier>ISSN: 1382-6689</identifier><identifier>EISSN: 1872-7077</identifier><identifier>DOI: 10.1016/j.etap.2018.10.004</identifier><identifier>PMID: 30391875</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adolescents ; Agricultural development ; Agrochemicals ; Amino acid neurotransmission ; Amino acid sequence ; Amino acids ; Animals ; Apoptosis ; Body weight ; Chronic exposure ; Circuits ; Cytotoxicity ; Demyelination ; Exposure ; Fungicides ; Fungicides, Industrial - toxicity ; Hazardous materials ; Hypothalamus ; Hypothalamus - drug effects ; Hypothalamus - metabolism ; Hypothalamus - pathology ; Hypothalamus - ultrastructure ; Inflammation ; Male ; Mancozeb ; Maneb - toxicity ; Mice ; Microscopy, Electron, Transmission ; Neonates ; Neuroendocrine system ; Neurosecretory cells ; Neurotoxicity ; Neurotransmitter Agents - metabolism ; Neurotransmitters ; Pesticides ; Toxicity ; Zineb - toxicity</subject><ispartof>Environmental toxicology and pharmacology, 2018-12, Vol.64, p.139-146</ispartof><rights>2018</rights><rights>Copyright © 2018. Published by Elsevier B.V.</rights><rights>Copyright Elsevier Science Ltd. Dec 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-22723c13596e8ad5af3213e558e99b15a2ed43be2f86fc6b25849a2c19f313253</citedby><cites>FETCH-LOGICAL-c384t-22723c13596e8ad5af3213e558e99b15a2ed43be2f86fc6b25849a2c19f313253</cites><orcidid>0000-0001-8169-9244</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.etap.2018.10.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30391875$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morales-Ovalles, Yasmin</creatorcontrib><creatorcontrib>Miranda-Contreras, Leticia</creatorcontrib><creatorcontrib>Peña-Contreras, Zulma</creatorcontrib><creatorcontrib>Dávila-Vera, Delsy</creatorcontrib><creatorcontrib>Balza-Quintero, Alirio</creatorcontrib><creatorcontrib>Sánchez-Gil, Beluardi</creatorcontrib><creatorcontrib>Mendoza-Briceño, Rosa Virginia</creatorcontrib><title>Developmental exposure to mancozeb induced neurochemical and morphological alterations in adult male mouse hypothalamus</title><title>Environmental toxicology and pharmacology</title><addtitle>Environ Toxicol Pharmacol</addtitle><description>•Developmental exposure altered amino acid neurotransmission in adult hypothalamus.•Variations in glutamate and GABA levels showed increased excitation/inhibition ratio.•Morphological changes revealed mitochondrial edema and demyelination in hypothalamus.
Mancozeb, a dithiocarbamate widely used in agriculture, is considered a developmental hazard in humans; however, more evidences are still needed concerning the consequences of chronic exposure to this pesticide. Mancozeb neurotoxicity in developing mouse hypothalamus was evaluated by subchronic exposure of male Mus musculus mice to low and high doses of mancozeb (30 and 90 mg/kg body weight, respectively) from late neonatal until adolescence. Variations in hypothalamic amino acid neurotransmitter levels and changes in histological as well as cytological characteristics were analyzed in young adult experimental mice and compared with control. A dose-dependent increase in excitation/ inhibition ratio was observed in mancozeb-exposed hypothalamus, indicating an overall state of excitoxicity. Histopathological and ultrastructural studies showed increased apoptosis, neuroinflammation and demyelination, demonstrating mancozeb-induced cytotoxicity in hypothalamic neurosecretory cells. In summary, both neurochemical and morphological data revealed mancozeb-induced alterations during development of hypothalamic circuitry that are critical for maturation of the neuroendocrine system.</description><subject>Adolescents</subject><subject>Agricultural development</subject><subject>Agrochemicals</subject><subject>Amino acid neurotransmission</subject><subject>Amino acid sequence</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Body weight</subject><subject>Chronic exposure</subject><subject>Circuits</subject><subject>Cytotoxicity</subject><subject>Demyelination</subject><subject>Exposure</subject><subject>Fungicides</subject><subject>Fungicides, Industrial - toxicity</subject><subject>Hazardous materials</subject><subject>Hypothalamus</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Hypothalamus - pathology</subject><subject>Hypothalamus - ultrastructure</subject><subject>Inflammation</subject><subject>Male</subject><subject>Mancozeb</subject><subject>Maneb - toxicity</subject><subject>Mice</subject><subject>Microscopy, Electron, Transmission</subject><subject>Neonates</subject><subject>Neuroendocrine system</subject><subject>Neurosecretory cells</subject><subject>Neurotoxicity</subject><subject>Neurotransmitter Agents - metabolism</subject><subject>Neurotransmitters</subject><subject>Pesticides</subject><subject>Toxicity</subject><subject>Zineb - toxicity</subject><issn>1382-6689</issn><issn>1872-7077</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAYRYMoOj7-gAspuG7NY9Im4EZ8g-BG1yFNvzod2qbmMTr-ejOMunSVcDn3hhyETgkuCCblxbKAoKeCYiJSUGA830EzIiqaV7iqdtOdCZqXpZAH6ND7JcaEMyb20QHDTCaQz9DHDaygt9MAY9B9Bp-T9dFBFmw26NHYL6izbmyigSYbITprFjB0JqF6bLLBumlhe_u2TfoATofOjj51Mt3EPqSVHhIXPWSL9WTDQvd6iP4Y7bW693Dycx6h17vbl-uH_On5_vH66ik3TMxDTmlFmSGMyxKEbrhuGSUMOBcgZU24ptDMWQ20FWVryppyMZeaGiJbRhjl7Aidb3cnZ98j-KCWNroxPako4VIyzCuWKLqljLPeO2jV5LpBu7UiWG1cq6XauFYb15ssuU6ls5_pWA_Q_FV-5SbgcgtA-uCqA6e86WBMKjsHJqjGdv_tfwP9_ZJP</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Morales-Ovalles, Yasmin</creator><creator>Miranda-Contreras, Leticia</creator><creator>Peña-Contreras, Zulma</creator><creator>Dávila-Vera, Delsy</creator><creator>Balza-Quintero, Alirio</creator><creator>Sánchez-Gil, Beluardi</creator><creator>Mendoza-Briceño, Rosa Virginia</creator><general>Elsevier B.V</general><general>Elsevier Science Ltd</general><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>7QP</scope><scope>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope><orcidid>https://orcid.org/0000-0001-8169-9244</orcidid></search><sort><creationdate>201812</creationdate><title>Developmental exposure to mancozeb induced neurochemical and morphological alterations in adult male mouse hypothalamus</title><author>Morales-Ovalles, Yasmin ; Miranda-Contreras, Leticia ; Peña-Contreras, Zulma ; Dávila-Vera, Delsy ; Balza-Quintero, Alirio ; Sánchez-Gil, Beluardi ; Mendoza-Briceño, Rosa Virginia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-22723c13596e8ad5af3213e558e99b15a2ed43be2f86fc6b25849a2c19f313253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescents</topic><topic>Agricultural development</topic><topic>Agrochemicals</topic><topic>Amino acid neurotransmission</topic><topic>Amino acid sequence</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Body weight</topic><topic>Chronic exposure</topic><topic>Circuits</topic><topic>Cytotoxicity</topic><topic>Demyelination</topic><topic>Exposure</topic><topic>Fungicides</topic><topic>Fungicides, Industrial - toxicity</topic><topic>Hazardous materials</topic><topic>Hypothalamus</topic><topic>Hypothalamus - drug effects</topic><topic>Hypothalamus - metabolism</topic><topic>Hypothalamus - pathology</topic><topic>Hypothalamus - ultrastructure</topic><topic>Inflammation</topic><topic>Male</topic><topic>Mancozeb</topic><topic>Maneb - toxicity</topic><topic>Mice</topic><topic>Microscopy, Electron, Transmission</topic><topic>Neonates</topic><topic>Neuroendocrine system</topic><topic>Neurosecretory cells</topic><topic>Neurotoxicity</topic><topic>Neurotransmitter Agents - metabolism</topic><topic>Neurotransmitters</topic><topic>Pesticides</topic><topic>Toxicity</topic><topic>Zineb - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morales-Ovalles, Yasmin</creatorcontrib><creatorcontrib>Miranda-Contreras, Leticia</creatorcontrib><creatorcontrib>Peña-Contreras, Zulma</creatorcontrib><creatorcontrib>Dávila-Vera, Delsy</creatorcontrib><creatorcontrib>Balza-Quintero, Alirio</creatorcontrib><creatorcontrib>Sánchez-Gil, Beluardi</creatorcontrib><creatorcontrib>Mendoza-Briceño, Rosa Virginia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><jtitle>Environmental toxicology and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morales-Ovalles, Yasmin</au><au>Miranda-Contreras, Leticia</au><au>Peña-Contreras, Zulma</au><au>Dávila-Vera, Delsy</au><au>Balza-Quintero, Alirio</au><au>Sánchez-Gil, Beluardi</au><au>Mendoza-Briceño, Rosa Virginia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Developmental exposure to mancozeb induced neurochemical and morphological alterations in adult male mouse hypothalamus</atitle><jtitle>Environmental toxicology and pharmacology</jtitle><addtitle>Environ Toxicol Pharmacol</addtitle><date>2018-12</date><risdate>2018</risdate><volume>64</volume><spage>139</spage><epage>146</epage><pages>139-146</pages><issn>1382-6689</issn><eissn>1872-7077</eissn><abstract>•Developmental exposure altered amino acid neurotransmission in adult hypothalamus.•Variations in glutamate and GABA levels showed increased excitation/inhibition ratio.•Morphological changes revealed mitochondrial edema and demyelination in hypothalamus.
Mancozeb, a dithiocarbamate widely used in agriculture, is considered a developmental hazard in humans; however, more evidences are still needed concerning the consequences of chronic exposure to this pesticide. Mancozeb neurotoxicity in developing mouse hypothalamus was evaluated by subchronic exposure of male Mus musculus mice to low and high doses of mancozeb (30 and 90 mg/kg body weight, respectively) from late neonatal until adolescence. Variations in hypothalamic amino acid neurotransmitter levels and changes in histological as well as cytological characteristics were analyzed in young adult experimental mice and compared with control. A dose-dependent increase in excitation/ inhibition ratio was observed in mancozeb-exposed hypothalamus, indicating an overall state of excitoxicity. Histopathological and ultrastructural studies showed increased apoptosis, neuroinflammation and demyelination, demonstrating mancozeb-induced cytotoxicity in hypothalamic neurosecretory cells. In summary, both neurochemical and morphological data revealed mancozeb-induced alterations during development of hypothalamic circuitry that are critical for maturation of the neuroendocrine system.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30391875</pmid><doi>10.1016/j.etap.2018.10.004</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-8169-9244</orcidid></addata></record> |
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| ispartof | Environmental toxicology and pharmacology, 2018-12, Vol.64, p.139-146 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Adolescents Agricultural development Agrochemicals Amino acid neurotransmission Amino acid sequence Amino acids Animals Apoptosis Body weight Chronic exposure Circuits Cytotoxicity Demyelination Exposure Fungicides Fungicides, Industrial - toxicity Hazardous materials Hypothalamus Hypothalamus - drug effects Hypothalamus - metabolism Hypothalamus - pathology Hypothalamus - ultrastructure Inflammation Male Mancozeb Maneb - toxicity Mice Microscopy, Electron, Transmission Neonates Neuroendocrine system Neurosecretory cells Neurotoxicity Neurotransmitter Agents - metabolism Neurotransmitters Pesticides Toxicity Zineb - toxicity |
| title | Developmental exposure to mancozeb induced neurochemical and morphological alterations in adult male mouse hypothalamus |
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