Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model
<b>Background/Objectives:</b> Fragile X Syndrome (FXS) is associated with intellectual disability, hyperactivity, social anxiety and signs of autism. Hyperactivation of NADPH oxidase has been previously described in the brain of the male <i>Fmr1</i>-KO mouse. This work aims t...
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2024-12-01
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| author | Yolanda de Diego-Otero Rajaa El Bekay Francisco García-Guirado Lourdes Sánchez-Salido Rosa María Giráldez-Pérez |
| author_facet | Yolanda de Diego-Otero Rajaa El Bekay Francisco García-Guirado Lourdes Sánchez-Salido Rosa María Giráldez-Pérez |
| author_sort | Yolanda de Diego-Otero |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Fragile X Syndrome (FXS) is associated with intellectual disability, hyperactivity, social anxiety and signs of autism. Hyperactivation of NADPH oxidase has been previously described in the brain of the male <i>Fmr1</i>-KO mouse. This work aims to demonstrate the efficacy of Apocynin, a specific NADPH oxidase inhibitor, in treating Fragile X mouse hallmarks. <b>Methods:</b> Free radicals, lipid and protein oxidation markers and behavioural and learning paradigms were measured after chronic treatment with orally administered vehicle, 10 mg/kg/day or 30 mg/kg/day of Apocynin. <b>Results</b>: The results revealed a reduction in testis weight, an increase in peritoneal fat, and no variation in body weight after chronic treatment. Furthermore, a reduction in hyperactivity was detected in Apocynin-treated male Fmr1-KO mice. Additionally, the higher dose of 30 mg/kg/day also improves behaviour and learning in the male Fmr1-KO mice, normalising free radical production and oxidative parameters. Moreover, a reduction in phospho-EKR1 and P47-Phox protein signals was observed in specific brain areas. <b>Conclusions</b>: Thus, chronic treatment with Apocynin could lead to a new therapeutic option for the Fragile X Syndrome. |
| format | Article |
| id | doaj-art-10c5560fcd1f4b68bdb8d88268e65cc1 |
| institution | DOAJ |
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| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-10c5560fcd1f4b68bdb8d88268e65cc12025-08-20T02:53:27ZengMDPI AGBiomedicines2227-90592024-12-011212288710.3390/biomedicines12122887Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse ModelYolanda de Diego-Otero0Rajaa El Bekay1Francisco García-Guirado2Lourdes Sánchez-Salido3Rosa María Giráldez-Pérez4Cellular Biology, Physiology and Immunology Department, University of Córdoba, 14014 Córdoba, SpainResearch Laboratory, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIO-NAND, Hospital Civil, 29009 Malaga, SpainResearch Laboratory, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIO-NAND, Hospital Civil, 29009 Malaga, SpainResearch Laboratory, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIO-NAND, Hospital Civil, 29009 Malaga, SpainCellular Biology, Physiology and Immunology Department, University of Córdoba, 14014 Córdoba, Spain<b>Background/Objectives:</b> Fragile X Syndrome (FXS) is associated with intellectual disability, hyperactivity, social anxiety and signs of autism. Hyperactivation of NADPH oxidase has been previously described in the brain of the male <i>Fmr1</i>-KO mouse. This work aims to demonstrate the efficacy of Apocynin, a specific NADPH oxidase inhibitor, in treating Fragile X mouse hallmarks. <b>Methods:</b> Free radicals, lipid and protein oxidation markers and behavioural and learning paradigms were measured after chronic treatment with orally administered vehicle, 10 mg/kg/day or 30 mg/kg/day of Apocynin. <b>Results</b>: The results revealed a reduction in testis weight, an increase in peritoneal fat, and no variation in body weight after chronic treatment. Furthermore, a reduction in hyperactivity was detected in Apocynin-treated male Fmr1-KO mice. Additionally, the higher dose of 30 mg/kg/day also improves behaviour and learning in the male Fmr1-KO mice, normalising free radical production and oxidative parameters. Moreover, a reduction in phospho-EKR1 and P47-Phox protein signals was observed in specific brain areas. <b>Conclusions</b>: Thus, chronic treatment with Apocynin could lead to a new therapeutic option for the Fragile X Syndrome.https://www.mdpi.com/2227-9059/12/12/2887fragile X syndromeApocyninNADPH-oxidasehyperactivitybehaviourlearning |
| spellingShingle | Yolanda de Diego-Otero Rajaa El Bekay Francisco García-Guirado Lourdes Sánchez-Salido Rosa María Giráldez-Pérez Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model Biomedicines fragile X syndrome Apocynin NADPH-oxidase hyperactivity behaviour learning |
| title | Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model |
| title_full | Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model |
| title_fullStr | Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model |
| title_full_unstemmed | Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model |
| title_short | Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model |
| title_sort | apocynin a selective nadph oxidase nox2 inhibitor ameliorates behavioural and learning deficits in the fragile x syndrome mouse model |
| topic | fragile X syndrome Apocynin NADPH-oxidase hyperactivity behaviour learning |
| url | https://www.mdpi.com/2227-9059/12/12/2887 |
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