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Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties
Huntington’s disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326416/ https://www.ncbi.nlm.nih.gov/pubmed/25675218 http://dx.doi.org/10.1371/journal.pone.0117223 |
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author | Menze, Esther T. Esmat, Ahmed Tadros, Mariane G. Abdel-Naim, Ashraf B. Khalifa, Amani E. |
author_facet | Menze, Esther T. Esmat, Ahmed Tadros, Mariane G. Abdel-Naim, Ashraf B. Khalifa, Amani E. |
author_sort | Menze, Esther T. |
collection | PubMed |
description | Huntington’s disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities. |
format | Online Article Text |
id | pubmed-4326416 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43264162015-02-24 Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties Menze, Esther T. Esmat, Ahmed Tadros, Mariane G. Abdel-Naim, Ashraf B. Khalifa, Amani E. PLoS One Research Article Huntington’s disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities. Public Library of Science 2015-02-12 /pmc/articles/PMC4326416/ /pubmed/25675218 http://dx.doi.org/10.1371/journal.pone.0117223 Text en © 2015 Menze et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Menze, Esther T. Esmat, Ahmed Tadros, Mariane G. Abdel-Naim, Ashraf B. Khalifa, Amani E. Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties |
title | Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties |
title_full | Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties |
title_fullStr | Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties |
title_full_unstemmed | Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties |
title_short | Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties |
title_sort | genistein improves 3-npa-induced memory impairment in ovariectomized rats: impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326416/ https://www.ncbi.nlm.nih.gov/pubmed/25675218 http://dx.doi.org/10.1371/journal.pone.0117223 |
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