Genistein inhibits aggregation of exogenous amyloid-beta(1-40) and alleviates astrogliosis in the hippocampus of rats
2012 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1429, 145-154 p.Article in journal (Refereed) Published
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.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-72775DOI: 10.1016/j.brainres.2011.10.020ISI: 000300268200016PubMedID: 22079317OAI: oai:DiVA.org:liu-72775DiVA: diva2:462361
funding agencies|Cellular and Molecular Research Center at Tehran University of Medical Sciences (Tehran)||Linkoping University (Linkoping, Sweden)||County Council of Ostergotland||2011-12-072011-12-072016-02-29Bibliographically approved