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Neuroprotective Effect of Genistein in 6-Hydroxydopamine Hemi-parkinsonian Rat Model
Iran University of Medical Sciences, Tehran.
Shahed University, Tehran.
Shahed University, Tehran.
Iran University of Medical Sciences.
2008 (English)In: Phytotherapy Research, ISSN 0951-418X, E-ISSN 1099-1573, Vol. 23, no 1, 132-135 p.Article in journal (Refereed) Published
Abstract [en]

A large body of experimental evidence supports a role for oxidative stress as a mediator of nerve cell death in Parkinson-s disease (PD). Phytoestrogens such as genistein have been reported to prevent neuronal degeneration caused by increased oxidative burden, therefore, this study examined whether genistein administration at a high dose would attenuate behavioral and structural abnormalities in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5 μg/5 μL of saline-ascorbate)- lesioned rats were intraperitoneally pretreated with a single and high dose of genistein (10 mg/kg) 1 h before surgery. Apomorphine-induced rotations and the number of Nissl-stained neurons in the substantia nigra pars compacta (SNC) were counted after 2 weeks. Genistein administration could attenuate the rotational behavior in lesioned rats and protect the neurons of SNC against 6-OHDA toxicity. Genistein administration has a protective effect against 6-OHDA toxicity. 

Place, publisher, year, edition, pages
2008. Vol. 23, no 1, 132-135 p.
Keyword [en]
genistein • Parkinson's disease • 6-hydroxydopamine • rotation • rat
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-44303DOI: 10.1002/ptr.2564PubMedID: 18693302Local ID: 76209OAI: oai:DiVA.org:liu-44303DiVA: diva2:265165
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
In thesis
1. Neuroprotective Effect of Genistein: Studies in Rat Models of Parkinson’s and Alzheimer’s Disease
Open this publication in new window or tab >>Neuroprotective Effect of Genistein: Studies in Rat Models of Parkinson’s and Alzheimer’s Disease
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders that mainly affect the elderly population. It is believed that oxidative stress is involved in development of both these diseases and that estrogen deficiency is a risk factor for development of AD. Genistein is a plant-derived compound that is similar in structure to estrogen and has anti-oxidative properties. The general objective of the present research was to evaluate the effects of genistein on neurodegeneration in rat models of PD and AD.

Using a rat model of PD, we found that a single intraperitoneal dose of genistein 1 h before intrastriatal injection of 6-hydroxydopamine (6-OHDA) attenuated apomorphine-induced rotational behavior and protected the neurons of substantia nigra pars compacta against 6-OHDA toxicity.

To produce an animal model of AD, we injected Aβ1–40 into the hippocampus of rats. Using groups of these Aβ1–40-lesioned animals, the involvement of estrogen receptors (ERs) was evaluated by intracerebroventricular injection of the estrogen receptor antagonist fulvestrant, and the role of oxidative stress was studied by measuring levels of malondialdehyde (MDA), nitrite, and superoxide dismutase (SOD) activity. The results showed that intrahippocampal injection of Aβ1–40 caused the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in a radial arm maze (RAM task), elevated levels of MDA and nitrite, and a signiHcant reduction in SOD activity in the brain tissue. Furthermore, hippocampus in theses rats exhibited Aβ1–40 immunoreactive aggregates close to the lateral blade of the dentate gyrus (DGlb), extensive neuronal degeneration in the DGlb, high intracellular iNOS+ and nNOS+ immunoreactivity, and extensive astrogliosis.

Genistein pretreatment ameliorated the Aβ-induced impairment of short-term spatial memory, and this effect occurred via an estrogenic pathway and through attenuation of oxidative stress. Genistein also ameliorated the degeneration of neurons, inhibited the formation of Aβ1–40-positive aggregates, and alleviated Aβ1–40-induced astrogliosis in the hippocampus.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1288
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77173 (URN)978-91-7519-984-9 (ISBN)
Public defence
2012-06-04, Berzeliussalen, Hälsouniversitetet, Campus Valla, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2012-05-07 Created: 2012-05-07 Last updated: 2016-02-29Bibliographically approved

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Bagheri, Maryam

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