{"id":1885,"date":"2023-09-26T21:42:41","date_gmt":"2023-09-27T00:42:41","guid":{"rendered":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/2023\/09\/26\/016-downregulation-of-redox-sensitive-transcription-factors-and-neuronal-ferroptosis-as-underlying-mechanisms-of-maneb-induced-toxicity\/"},"modified":"2023-09-26T22:20:31","modified_gmt":"2023-09-27T01:20:31","slug":"016-downregulation-of-redox-sensitive-transcription-factors-and-neuronal-ferroptosis-as-underlying-mechanisms-of-maneb-induced-toxicity","status":"publish","type":"post","link":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/2023\/09\/26\/016-downregulation-of-redox-sensitive-transcription-factors-and-neuronal-ferroptosis-as-underlying-mechanisms-of-maneb-induced-toxicity\/","title":{"rendered":"016 | DOWNREGULATION OF REDOX-SENSITIVE TRANSCRIPTION FACTORS AND NEURONAL FERROPTOSIS AS UNDERLYING MECHANISMS OF MANEB-INDUCED TOXICITY"},"content":{"rendered":"<p>Cellular and Molecular Neurobiology<\/p>\n<p><strong>Author:<\/strong> Melisa Ailen Conde | <strong>Email:<\/strong> mconde@inibibb-conicet.gob.ar<\/p>\n<hr \/>\n<p>Melisa Ailen Conde <sup>2\u00b0<\/sup>, Oriana Nicole Benzi Juncos <sup>2\u00b0<\/sup>, Athina del Valle Maniscalchi <sup>1\u00b0<\/sup>, Melania Iara Funk <sup>1\u00b0<\/sup>, Natalia Paola Alza <sup>3\u00b0<\/sup>, Gabriela Alejandra Salvador <sup>2\u00b0<\/sup><\/p>\n<p>1\u00b0 Instituto de Investigaciones Bioqu\u00edmicas de Bah\u00eda Blanca, Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas.<br \/>\n2\u00b0 Instituto de Investigaciones Bioqu\u00edmicas de Bah\u00eda Blanca, Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas &#8211; Departamento de Biolog\u00eda, Bioqu\u00edmica y Farmacia, UNS.<br \/>\n3\u00b0 Instituto de Investigaciones Bioqu\u00edmicas de Bah\u00eda Blanca, Universidad Nacional del Sur (UNS), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas &#8211; Departamento de Qu\u00edmica, UNS.<\/p>\n<p>Epidemiological studies provide evidence of a strong association between the use of dithiocarbamate pesticides, such as Maneb (MB), and the risk of Parkinson&#8217;s disease. Here, we tested the hypothesis that MB increases \u03b1-synuclein expression and downregulates several redox-sensitive transcription factors, thus promoting neuronal death. For this purpose, we challenged neuronal and primary glial cultures, and mice with MB. When exposed to MB, neurons showed \u03b1-synuclein upregulation accompanied by markers of oxidative stress. This was associated with diminished glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 mRNA expression and upregulation of the NRF2 repressor, BACH1. MB treatment also downregulated glutathione peroxidase 4 mRNA levels in neurons, which was coincident with increased content of reactive oxygen species, lipid peroxidation, and mitochondrial alterations. These deleterious effects were prevented by treating MB-exposed neurons with ferrostatin-1, an inhibitor of ferroptosis. In glial cell cultures, MB triggered microglial and astrocyte activation. In mice, MB-induced neurodegeneration provoked motor impairment associated with enhanced \u03b1-synuclein expression in midbrain. Our results show that MB-induced neurotoxicity downregulates NRF2 pathway and elicits neuronal death probably triggering mechanisms associated with ferroptosis.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Author: Conde Melisa Ailen | email: mconde@inibibb-conicet.gob.ar | Cellular and Molecular Neurobiology<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[18],"class_list":["post-1885","post","type-post","status-publish","format-standard","hentry","category-session-2","tag-cellular-and-molecular-neurobiology"],"_links":{"self":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1885","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/comments?post=1885"}],"version-history":[{"count":1,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1885\/revisions"}],"predecessor-version":[{"id":2033,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/posts\/1885\/revisions\/2033"}],"wp:attachment":[{"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/media?parent=1885"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/categories?post=1885"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csan2023.saneurociencias.org.ar\/index.php\/wp-json\/wp\/v2\/tags?post=1885"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}