Autophagy-dependent mechanism of genistein-mediated elimination of behavioral and biochemical defects in the rat model of sporadic Alzheimer's disease

Karolina Pierzynowska , Magdalena Podlacha , Lidia Gaffke , Irena Majkutewicz , Jagoda Mantej , Alicja Węgrzyn , Marta Osiadły , Dorota Myślińska , Grzegorz Węgrzyn

Abstract

Alzheimer's disease is one of severe neurological diseases for which no effective treatment is currently available. The use of genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) has been proposed previously as one of approaches to improve the disease symptoms, as some positive effects of this compound in cellular and animal models were reported. Inhibition of apoptosis and antioxidative functions were suggested as causes of these effects. Here, we demonstrate that high genistein dose (150 mg/kg/day; the dose significantly higher than those used previously in AD studies by others) can activate autophagy in the streptozotocin-induced rat model of the sporadic form of AD. We found that this dose of genistein led to complete degradation of β-amyloid and hyperphosphorylated tau protein in the brain, while experiments with cell cultures demonstrated that these effects require autophagy stimulation, which has never been shown before. Importantly, behavior of high dose genistein-treated AD rats was completely corrected, i.e. it was indistinguishable from that of healthy animals. This was observed in all performed behavioral tests: Morris water maze test, elevated plus-maze test, open field test, and locomotor measurements in an actometer. We conclude that autophagy-dependent mechanism is responsible for genistein-mediated correction of AD when this isoflavone is used at the high dose.
Author Karolina Pierzynowska (FB / DMoB)
Karolina Pierzynowska,,
- Department of Molecular Biology
, Magdalena Podlacha (FB / DAHP)
Magdalena Podlacha,,
- Department of Animal and Human Physiology
, Lidia Gaffke (FB / DMoB)
Lidia Gaffke,,
- Department of Molecular Biology
, Irena Majkutewicz (FB / DAHP)
Irena Majkutewicz,,
- Department of Animal and Human Physiology
, Jagoda Mantej (FB / DMoB)
Jagoda Mantej,,
- Department of Molecular Biology
, Alicja Węgrzyn
Alicja Węgrzyn,,
-
, Marta Osiadły (FB)
Marta Osiadły,,
- Faculty of Biology
, Dorota Myślińska (FB / DAHP)
Dorota Myślińska,,
- Department of Animal and Human Physiology
, Grzegorz Węgrzyn (FB / DMoB)
Grzegorz Węgrzyn,,
- Department of Molecular Biology
Journal seriesNeuropharmacology, ISSN 0028-3908, e-ISSN 1873-7064, (N/A 140 pkt)
Issue year2019
Vol148
Pages332-346
Publication size in sheets0.7
Keywords in EnglishAlzheimer's disease, autophagy, genistein, streptozotocin, rat model, correction of behavior, β-amyloid, hyperphosphorylated tau protein
ASJC Classification2804 Cellular and Molecular Neuroscience; 3004 Pharmacology
DOIDOI:10.1016/j.neuropharm.2019.01.030
Languageen angielski
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 28-01-2020, ArticleFromJournal
Publication indicators WoS Citations = 3; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.212; WoS Impact Factor: 2018 = 4.367 (2) - 2018=4.494 (5)
Citation count*5 (2020-03-30)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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