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Genistein inhibits Aβ1-40-induced astrogliosis: A three-dimensional confocal morphometric analysis
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Department of Physiology, Neurophysiology Research Group, Shahed University, Tehran, Iran.
Cellular and Molecular Research Center & Department of Anatomy and Neuroscience, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Astrocytes are highly involved in regulation and homeostasis of the extracellular environment in the healthy brain. In pathological conditions, these cells play a major role in the inflammatory response seen in CNS tissues, which is called reactive astrogliosis and includes hypertrophy, proliferation, and remodeling. Here, we performed 3D confocal microscopy to evaluate the morphology of reactive glial fibrillary acidic protein (GFAP-positive) astrocytes in an animal model of Alzheimer’s disease, and we also assessed the effect of the antiinflammatory agent genistein on amyloid-beta-induced astrogliosis. In 50 astrocytes/animal, we measured the area and volume of the nucleus, cell body, astrocyte (soma and branches) and territory (tissue covered by each astrocyte), and total length of the branches. Moreover, we quantified the intensity of GFAP immunoreactivity in the hippocampus. Injecting amyloid beta (Aβ)1–40 into the brain caused astrogliosis, observed as significantly higher GFAP intensity in the hippocampus, and also led to significant enlargement of astrocytes in this area, indicated by increased values for all the above-mentioned parameters. In Aβ1–40-injected rats pretreated with genistein, GFAP intensity was decreased to the level seen in the shamoperated group, and Aβ1–40-induced enlargement of astrocytes was significantly inhibited. Interestingly, genistein also ameliorated the astrogliosis that was initiated by mechanical injury caused by insertion of the injection needle into the brain tissue. This  was indicated by the observation that the mean cell body volume and area of astrocytes were significantly smaller in the genistein-treated rats, even in comparison with the sham-operated animals.

Keyword [en]
Alzheimer’s disease; astrocytes; amyloid beta; genistein; gliosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-77172OAI: oai:DiVA.org:liu-77172DiVA: diva2:525325
Available from: 2012-05-07 Created: 2012-05-07 Last updated: 2016-02-29Bibliographically 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)
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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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