Suppression of NF-κβ signaling pathway by tocotrienol can prevent diabetes associated cognitive deficits

被引:139
作者
Kuhad, Anurag [1 ]
Bishnoi, Mahendra [1 ]
Tiwari, Vinod [1 ]
Chopra, Kanwaljit [1 ]
机构
[1] Panjab Univ, UGC Ctr Adv Study, Univ Inst Pharmaceut Sci, Pharmacol Res Lab, Chandigarh 160014, India
关键词
Apoptosis; Acetylcholinesterase; Caspase-3; Diabetic encephalopathy; IL-1; beta; NF kappa beta; Oxidative-nitrosative stress; Tocotrienol; TNF-alpha; TUMOR-NECROSIS-FACTOR; ALPHA-TOCOTRIENOL; OXIDATIVE STRESS; REACTIVE OXYGEN; VITAMIN-E; ANTIOXIDANT PROPERTIES; MEDIATED APOPTOSIS; RECEPTOR; STREPTOZOTOCIN; ACTIVATION;
D O I
10.1016/j.pbb.2008.12.012
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Objective: The etiology of diabetes associated cognitive decline is multifactorial and involves insulin receptor down regulation, neuronal apoptosis and glutamatergic neurotransmission. The study was designed to evaluate the impact of tocotrienol oil cognitive function and neuroinflammatory cascade in streptozotocin-induced diabetes. Research design and-method: Streptozotocin-induced diabetic rats were treated with tocotrienol for 10 weeks. Morris water maze Was used for behavioral assessment of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of acetylcholinesterase activity, oxidative-nitrosative stress. tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), NF kappa beta and caspase-3. Results: After 10 weeks of streptozotocin injection, the rats produced significant increase in transfer latency which Was Coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, TNF-alpha, caspase-3 activity and active p65 subunit of NF kappa beta in different regions of diabetic rat brain. Interestingly. co-administration of tocotrienol significantly and dose-dependently prevented behavioral, biochemical and molecular changes associated with diabetes. Moreover, diabetic rats treated with insulin-tocotrienol combination produced more, pronounced effect Oil molecular parameters as compared to their per se groups. Conclusions: Collectively, the data reveal that activation of NF kappa beta signaling pathway is associated with diabetes induced cognitive impairment and point towards the therapeutic potential of tocotrienol in diabetic encephalopathy. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:251 / 259
页数:9
相关论文
共 55 条
[1]   γ-tocotrienol inhibits nuclear factor-κB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and Potentiation of apoptosis [J].
Ahn, Kwang Seok ;
Sethi, Gautam ;
Krishnan, Koyamangalath ;
Aggarwal, Bharat B. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (01) :809-820
[2]   Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function [J].
Arvanitakis, Z ;
Wilson, RS ;
Bienias, JL ;
Evans, DA ;
Bennett, DA .
ARCHIVES OF NEUROLOGY, 2004, 61 (05) :661-666
[3]   Reactive oxygen as modulator of TNF and Fas receptor-mediated apoptosis in vivo:: Studies with glutathione peroxidase-deficient mice [J].
Bajt, ML ;
Ho, YS ;
Vonderfecht, SL ;
Jaeschke, H .
ANTIOXIDANTS & REDOX SIGNALING, 2002, 4 (05) :733-740
[4]   The p75 neurotrophin receptor and neuronal apoptosis [J].
Barrett, GL .
PROGRESS IN NEUROBIOLOGY, 2000, 61 (02) :205-229
[5]  
Begum AN, 2002, BIOSCI BIOTECH BIOCH, V66, P398, DOI 10.1271/bbb.66.398
[6]   Glucose and reactive oxygen species [J].
Bonnefont-Rousselot, D .
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE, 2002, 5 (05) :561-568
[7]   Cerebral dysfunction in type 1 diabetes: effects of insulin, vascular risk factors and blood-glucose levels [J].
Brands, AMA ;
Kessels, RPC ;
de Haan, EHF ;
Kappelle, LJ ;
Biessels, GJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 490 (1-3) :159-168
[8]   Biochemistry and molecular cell biology of diabetic complications [J].
Brownlee, M .
NATURE, 2001, 414 (6865) :813-820
[9]   Apoptosis-inducing factor (AIF):: caspase-independent after all [J].
Candé, C ;
Vahsen, N ;
Garrido, C ;
Kroemer, G .
CELL DEATH AND DIFFERENTIATION, 2004, 11 (06) :591-595
[10]  
Claiborne A., 1985, CRC handbook of methods for oxygen radical research, V1, P283, DOI DOI 10.1016/0531-5565(85)90021-X