The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain
Ochratoxin A (OTA) is a common secondary metabolite of <i>Aspergillus ochraceus</i>, <i>A. carbonarius</i>, and <i>Penicillium verrucosum</i>. This mycotoxin is largely present as a contaminant in several cereal crops and human foodstuffs, including grapes, corn,...
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MDPI AG
2022-09-01
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| author | Eva Mateo Rik Paulus Bernardus Tonino Antolin Canto Antonio Monroy Noyola Maria Miranda Jose Miguel Soria María Angeles Garcia Esparza |
| author_facet | Eva Mateo Rik Paulus Bernardus Tonino Antolin Canto Antonio Monroy Noyola Maria Miranda Jose Miguel Soria María Angeles Garcia Esparza |
| author_sort | Eva Mateo |
| collection | DOAJ |
| description | Ochratoxin A (OTA) is a common secondary metabolite of <i>Aspergillus ochraceus</i>, <i>A. carbonarius</i>, and <i>Penicillium verrucosum</i>. This mycotoxin is largely present as a contaminant in several cereal crops and human foodstuffs, including grapes, corn, nuts, and figs, among others. Preclinical studies have reported the involvement of OTA in metabolic, physiologic, and immunologic disturbances as well as in carcinogenesis. More recently, it has also been suggested that OTA may impair hippocampal neurogenesis in vivo and that this might be associated with learning and memory deficits. Furthermore, aside from its widely proven toxicity in tissues other than the brain, there is reason to believe that OTA contributes to neurodegenerative disorders. Thus, in this present in vivo study, we investigated this possibility by intraperitoneally (i.p.) administering 3.5 mg OTA/kg body weight to adult male mice to assess whether chronic exposure to this mycotoxin negatively affects cell viability in the dentate gyrus of the hippocampus. Immunohistochemistry assays showed that doses of 3.5 mg/kg caused a significant and dose-dependent reduction in repetitive cell division and branching (from 12% to 62%). Moreover, the number of countable astrocytes (<i>p</i> < 0.001), young neurons (<i>p</i> < 0.001), and mature neurons (<i>p</i> < 0.001) negatively correlated with the number of i.p. OTA injections administered (one, two, three, or six repeated doses). Our results show that OTA induced adverse effects in the hippocampus cells of adult mice brain tissue when administered in cumulative doses. |
| first_indexed | 2024-03-09T22:19:23Z |
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| language | English |
| last_indexed | 2024-03-09T22:19:23Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Toxins |
| spelling | doaj.art-949373ca8e294d028c0941ae67c40e1b2023-11-23T19:16:55ZengMDPI AGToxins2072-66512022-09-0114962410.3390/toxins14090624The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse BrainEva Mateo0Rik Paulus Bernardus Tonino1Antolin Canto2Antonio Monroy Noyola3Maria Miranda4Jose Miguel Soria5María Angeles Garcia Esparza6Department of Microbiology and Ecology, School of Medicine and Dentistry, University of Valencia, 46001 Valencia, SpainHaematology Department, Leiden University, 1043 AJ Leiden, The NetherlandsDepartment of Biomedical Sciences, Cardenal Herrera University-CEU Universities, 46001 Valencia, SpainNeuroprotection Laboratory, Faculty of Pharmacy, Autonomous University of the State of Morelos, Cuernavaca, Morelos 98100, MexicoDepartment of Biomedical Sciences, Cardenal Herrera University-CEU Universities, 46001 Valencia, SpainDepartment of Biomedical Sciences, Cardenal Herrera University-CEU Universities, 46001 Valencia, SpainDepartment of Pharmacy, Cardenal Herrera University-CEU Universities, 46001 Valencia, SpainOchratoxin A (OTA) is a common secondary metabolite of <i>Aspergillus ochraceus</i>, <i>A. carbonarius</i>, and <i>Penicillium verrucosum</i>. This mycotoxin is largely present as a contaminant in several cereal crops and human foodstuffs, including grapes, corn, nuts, and figs, among others. Preclinical studies have reported the involvement of OTA in metabolic, physiologic, and immunologic disturbances as well as in carcinogenesis. More recently, it has also been suggested that OTA may impair hippocampal neurogenesis in vivo and that this might be associated with learning and memory deficits. Furthermore, aside from its widely proven toxicity in tissues other than the brain, there is reason to believe that OTA contributes to neurodegenerative disorders. Thus, in this present in vivo study, we investigated this possibility by intraperitoneally (i.p.) administering 3.5 mg OTA/kg body weight to adult male mice to assess whether chronic exposure to this mycotoxin negatively affects cell viability in the dentate gyrus of the hippocampus. Immunohistochemistry assays showed that doses of 3.5 mg/kg caused a significant and dose-dependent reduction in repetitive cell division and branching (from 12% to 62%). Moreover, the number of countable astrocytes (<i>p</i> < 0.001), young neurons (<i>p</i> < 0.001), and mature neurons (<i>p</i> < 0.001) negatively correlated with the number of i.p. OTA injections administered (one, two, three, or six repeated doses). Our results show that OTA induced adverse effects in the hippocampus cells of adult mice brain tissue when administered in cumulative doses.https://www.mdpi.com/2072-6651/14/9/624ochratoxin Abrainhippocampusneurogenic nicheneurotoxicitycell morphology |
| spellingShingle | Eva Mateo Rik Paulus Bernardus Tonino Antolin Canto Antonio Monroy Noyola Maria Miranda Jose Miguel Soria María Angeles Garcia Esparza The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain Toxins ochratoxin A brain hippocampus neurogenic niche neurotoxicity cell morphology |
| title | The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain |
| title_full | The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain |
| title_fullStr | The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain |
| title_full_unstemmed | The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain |
| title_short | The Neurotoxic Effect of Ochratoxin-A on the Hippocampal Neurogenic Niche of Adult Mouse Brain |
| title_sort | neurotoxic effect of ochratoxin a on the hippocampal neurogenic niche of adult mouse brain |
| topic | ochratoxin A brain hippocampus neurogenic niche neurotoxicity cell morphology |
| url | https://www.mdpi.com/2072-6651/14/9/624 |
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