Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase IV protein levels in Alzheimer's disease model rats

被引:56
作者
Ye, Shu [1 ]
Wang, Ting-ting [1 ]
Cai, Biao [1 ,2 ]
Wang, Yan [1 ,2 ]
Li, Jing [1 ,2 ]
Zhan, Ji-xian [1 ]
Shen, Guo-ming [1 ,2 ]
机构
[1] Anhui Univ Chinese Med, Sch Integrated Chinese & Western Med, Hefei, Anhui, Peoples R China
[2] Anhui Acad Chinese Med, Inst Integrated Chinese & Western Med, Hefei, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
nerve regeneration; neurodegeneration; genistein; Alzheimer's disease; neuroprotection; hippocampus; learning; memory; tau protein; CAMK4; CALM; CAMKK1; neural regeneration; MORRIS WATER MAZE; AMYLOID-BETA; TAU; ACTIVATION; EXPRESSION; AGGREGATION; PATHWAY; MEMORY; CELLS; LEADS;
D O I
10.4103/1673-5374.215260
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Genistein has a neuroprotective effect in Alzheimer's disease, but its mechanism of action needs further clarification. Accumulating evidence suggests that excessive phosphorylation of tau protein causes production of neurofibrillary tangles, which is one of the main pathological characteristics of Alzheimer's disease, and tau protein can be phosphorylated by calcium/ calmodulin dependent protein kinase IV (CAMK4). After 7 days of pre-administration of genistein (90 mg/kg), an Alzheimer's disease rat model was established using an intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-beta peptide (25-35). The rat was then continuously administered genistein (90 mg/kg) for 42 days. The Morris water maze test, western blotting and hematoxylin-eosin staining results showed that genistein significantly decreased the escape latency and increased the number of times crossing the platform, reduced p-tau, CALM, CAMKK1 and p-CAMK4 protein levels in the hippocampus, and alleviated hippocampal neuron damage. These findings indicate that genistein may play a neuroprotective role in Alzheimer's disease through regulating CAMK4 to modulate tau hyperphosphorylation.
引用
收藏
页码:1479 / 1484
页数:6
相关论文
共 33 条
  • [1] Amyloid-β and Tau The Trigger and Bullet in Alzheimer Disease Pathogenesis
    Bloom, George S.
    [J]. JAMA NEUROLOGY, 2014, 71 (04) : 505 - 508
  • [2] Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease
    Bonet-Costa, Vicent
    Herranz-Perez, Vicente
    Blanco-Gandia, MariCarmen
    Mas-Bargues, Cristina
    Ingles, Marta
    Garcia-Tarraga, Patricia
    Rodriguez-Arias, Marta
    Minarro, Jose
    Borras, Consuelo
    Manuel Garcia-Verdugo, Jose
    Vina, Jose
    [J]. JOURNAL OF ALZHEIMERS DISEASE, 2016, 51 (03) : 701 - 711
  • [3] Enhanced expression of sodium hydrogen exchanger (NHE)-1, 2 and 4 in the uteri of rat model for post-menopause under phytoestrogen genistein influence
    Chinigarzadeh, Asma
    Muniandy, Sekaran
    Salleh, Naguib
    [J]. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 2015, 40 (01) : 39 - 48
  • [4] Regulation of the activities of multifunctional Ca2+/calmodulin-dependent protein kinases
    Fujisawa, H
    [J]. JOURNAL OF BIOCHEMISTRY, 2001, 129 (02) : 193 - 199
  • [5] Effects of early protein malnutrition and scopolamine on learning and memory in the Morris water maze
    Fukuda, M. T. H.
    Francolin-Silva, A. L.
    Hernandes, A. S.
    Valadares, C. T.
    Almeida, S. S.
    [J]. NUTRITIONAL NEUROSCIENCE, 2007, 10 (5-6) : 251 - 259
  • [6] Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging
    Fukushima, Hotaka
    Maeda, Ryouta
    Suzuki, Ryousuke
    Suzuki, Akinobu
    Nomoto, Masanori
    Toyoda, Hiroki
    Wu, Long-Jun
    Xu, Hui
    Zhao, Ming-Gao
    Ueda, Kenji
    Kitamoto, Aya
    Mamiya, Nori
    Yoshida, Taro
    Homma, Seiichi
    Masushige, Shoichi
    Zhuo, Min
    Kida, Satoshi
    [J]. JOURNAL OF NEUROSCIENCE, 2008, 28 (40) : 9910 - 9919
  • [7] Differential toxicity, conformation and morphology of typical initial aggregation states of Aβ1-42 and Aβpy3-42 beta-amyloids
    Galante, Denise
    Corsaro, Alessandro
    Florio, Tullio
    Vella, Serena
    Pagano, Aldo
    Sbrana, Francesca
    Vassalli, Massimo
    Perico, Angelo
    D'Arrigo, Cristina
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2012, 44 (11) : 2085 - 2093
  • [8] Gong CX, 2006, J ALZHEIMERS DIS, V9, P1
  • [9] Genistein ameliorates cardiac inflammation and oxidative stress in streptozotocin-induced diabetic cardiomyopathy in rats
    Gupta, Suresh K.
    Dongare, Shirish
    Mathur, Rajani
    Mohanty, Ipseeta Ray
    Srivastava, Sushma
    Mathur, Sandeep
    Nag, Tapas C.
    [J]. MOLECULAR AND CELLULAR BIOCHEMISTRY, 2015, 408 (1-2) : 63 - 72
  • [10] Tau phosphorylation: the therapeutic challenge for neurodegenerative disease
    Hanger, Diane P.
    Anderton, Brian H.
    Noble, Wendy
    [J]. TRENDS IN MOLECULAR MEDICINE, 2009, 15 (03) : 112 - 119