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Genistein inhibits aggregation of exogenous amyloid-beta(1-40) and alleviates astrogliosis in the hippocampus of rats
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Shahed University.
Tehran University of Medical Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-1342-369X
2012 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1429, 145-154 p.Article in journal (Refereed) Published
Abstract [en]

We addressed the question of whether injection of Amyloid beta (Aβ)(1-40) in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aβ(1-40). Genistein is a plant-derived compound with a structure similar to that of the female sex hormone estrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an (Aβ)(1-40) rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aβ(1-40) positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P<0.0001), CA1 (P=0.03), and CA3 (P=0.002); an increased number of iNOS-expressing cells (P=0.01) and gliosis. Genistein given to rats by gavage 1h before injection of Aβ(1-40) inhibited the formation of Aβ(1-40) positive aggregates in the brain tissue and led to increased number of nNOS(+) (P=0.0001) cells in the hippocampus compared to sham-operated genistein-treated controls. Treatment with genistein also alleviated the extensive astrogliosis that occurred in Aβ(1-40)-injected hippocampus to a level similar to that observed in sham-operated rats. We conclude that the neurons in the DGlb are most sensitive to Aβ(1-40), and a single dose of genistein can ameliorate Aβ(1-40) induced pathology.

Place, publisher, year, edition, pages
Elsevier, 2012. Vol. 1429, 145-154 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-72775DOI: 10.1016/j.brainres.2011.10.020ISI: 000300268200016PubMedID: 22079317OAI: oai:DiVA.org:liu-72775DiVA: diva2:462361
Note
funding agencies|Cellular and Molecular Research Center at Tehran University of Medical Sciences (Tehran)||Linkoping University (Linkoping, Sweden)||County Council of Ostergotland||Available from: 2011-12-07 Created: 2011-12-07 Last updated: 2017-12-08Bibliographically approved
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, MaryamMohseni, Simin

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