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Journal of Neurorestoratology  2017, Vol. 5 Issue (1): 117-123    doi: 10.2147/JN.S125567
Original Research     
Curcumin reduces hippocampal neuron apoptosis and JNK-3 phosphorylation in rats with Aβ-induced Alzheimer’s disease: protecting spatial learning and memory
Yun-liang Wang1,2,*, Jin-feng Li1,*, Yu-tong Wang3, Chun-yang Xu2, Lin-lin Hua2, Xiao-peng Yang2, Shuang Geng1, Shan-shan Wang1, Zhen Wang1, Hong-lei Yin1
1 Neurology Department, 148th Hospital, Zibo, Shandong;
2 Neurology Department, Second Affiliated Hospital of Zhengzhou University, Zhengzhou;
3 Public Health Department, Henan University School of Medicine, Kaifeng, Henan, People’s Republic of China
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Abstract  Amyloid-β peptide (Aβ) toxicity in Alzheimer’s disease (AD) is associated with the c-Jun N-terminal kinase (JNK) signaling pathway. Curcumin may prevent Aβ fiber formation, slowing AD progression. A model of AD was established in 32 Sprague Dawley rats by injection of 10 μg Aβ1-40 into the right hippocampus. Saline was used in sham control (n=16). Sixteen AD model rats received 300 mg/kg curcumin and another 16 received saline daily for 7 days. Spatial learning and memory were assessed using a Morris water maze. Hippocampus neuron apoptosis and hippocampal levels of JNK-3 and p-JNK-3 were assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling, reverse transcription-polymerase chain reaction and Western blotting. Aβ1-40 injection induced slower spatial learning, memory deficit, neuronal apoptosis and increased JNK-3 expression and phosphorylation (all P<0.05). Curcumin relieved spatial learning and memory deficits, hippocampus neuronal apoptosis, and reduced JNK-3 and p-JNK-3 levels (all P<0.05). In conclusion, curcumin may inhibit JNK-3 phosphorylation to protect against hippocampal neuron apoptosis after Aβ injection.

Key wordsAlzheimer's disease      curcumin      apoptosis      JNK-3      phosphorylation     
Received: 24 October 2016      Published: 26 December 2017
Corresponding Authors: Hong-lei Yin, Neurology Department, 148th Hospital, 20 Zhanbei Road, Zibo, Shandong, 255300, People’s Republic of China Tel +86 533 655 2183 Fax +86 533 655 2100 Email Yinhonglei1981@126.com; *These authors contributed equally to this work   
Cite this article:

Yun-liang Wang, Jin-feng Li, Yu-tong Wang, Chun-yang Xu, Lin-lin Hua, Xiao-peng Yang, Shuang Geng, Shan-shan Wang, Zhen Wang, Hong-lei Yin. Curcumin reduces hippocampal neuron apoptosis and JNK-3 phosphorylation in rats with Aβ-induced Alzheimer’s disease: protecting spatial learning and memory. Journal of Neurorestoratology, 2017, 5: 117-123.

URL:

http://jnr.tsinghuajournals.com/10.2147/JN.S125567     OR     http://jnr.tsinghuajournals.com/Y2017/V5/I1/117

1. Zhang Y, Xu Y, Nie H, et al.Prevalence of dementia and major dementia subtypes in the Chinese populations: a meta-analysis of dementia prevalence surveys, 1980-2010.J Clin Neurosci. 2012;19(10):1333-1337.
2. Mielke MM, Vemuri P, Rocca WA.Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences.Clin Epidemiol. 2014; 6:37-48.
3. Lucey BP, Bateman RJ.Amyloid-beta diurnal pattern: possible role of sleep in Alzheimer’s disease pathogenesis.Neurobiol Aging. 2014; 35(Suppl 2):S29-S34.
4. Qiao L, Huang H, Muresanu DF.Clinical neurorestorative progress in Alzheimer’s disease.Journal of Neurorestoratology. 2015; 3:1-9.
5. Zhu H, Fu W, Mattson MP.The catalytic subunit of telomerase protects neurons against amyloid beta-peptide-induced apoptosis. J Neurochem. 2000;75(1):117-124.
6. McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy.Acta Neuropathol. 2013;126(4):479-497.
7. Borsello T, Forloni G.JNK signalling: a possible target to prevent neurodegeneration.Curr Pharm Des. 2007;13(18):1875-1886.
8. Yoon SO, Park DJ, Ryu JC, et al.JNK3 perpetuates metabolic stress induced by Abeta peptides.Neuron. 2012;75(5):824-837.
9. Kuan CY, Whitmarsh AJ, Yang DD, et al.A critical role of neural-specific JNK3 for ischemic apoptosis.Proc Natl Acad Sci U S A. 2003;100(25):15184-15189.
10. Xu Y, Hou XY, Liu Y, Zong YY.Different protection of K252a and N-acetyl-L-cysteine against amyloid-beta peptide-induced cortical neuron apoptosis involving inhibition of MLK3-MKK7-JNK3 signal cascades.J Neurosci Res. 2009;87(4):918-927.
11. Bogoyevitch MA.The isoform-specific functions of the c-Jun N-terminal kinases (JNKs): differences revealed by gene targeting.Bioessays. 2006;28(9):923-934.
12. Joe B, Vijaykumar M, Lokesh BR.Biological properties of curcumin-cellular and molecular mechanisms of action.Crit Rev Food Sci Nutr. 2004;44(2):97-111.
13. Zhou Y, Su Y, Li B, et al.Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho.Science. 2003; 302(5648):1215-1217.
14. Cole GM, Morihara T, Lim GP, Yang F, Begum A, Frautschy SA.NSAID and antioxidant prevention of Alzheimer’s disease: lessons from in vitro and animal models.Ann N Y Acad Sci. 2004;1035:68-84.
15. Begum AN, Jones MR, Lim GP, et al.Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease.J Pharmacol Exp Ther. 2008;326(1):196-208.
16. Yang F, Lim GP, Begum AN, et al.Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo.J Biol Chem. 2005;280(7):5892-5901.
17. Ma QL, Yang F, Rosario ER, et al.Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin.J Neurosci. 2009;29(28):9078-9089.
18. Rissman RA, Mishizen-Eberz AJ, Carter TL, et al.Biochemical analysis of GABA(A) receptor subunits alpha 1, alpha 5, beta 1, beta 2 in the hippocampus of patients with Alzheimer’s disease neuropathology.Neuroscience. 2003;120(3):695-704.
19 19. Qiu G, Wu XQ, Luo XG. [Effect of polygonum multiflorum thunb on BDNF expression in rat hippocampus induced by amyloid beta-protein (Abeta) 1-40].Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006; 31(2):194-199.
20. Khazipov R, Zaynutdinova D, Ogievetsky E, et al.Atlas of the Postnatal Rat Brain in Stereotaxic Coordinates.Front Neuroanat. 2015;9:161.
21. Fan H, Guo Y, Liang X, et al.Hydrogen sulfide protects against amyloid beta-peptide induced neuronal injury via attenuating inflammatory responses in a rat model. [J] Biomed Res. 2013;27(4):296-304.
22. Rahimian R, Fakhfouri G, Ejtemaei Mehr S, et al.Tropisetron attenuates amyloid-beta-induced inflammatory and apoptotic responses in rats. Eur J Clin Invest. 2013;43(10):1039-1051.
23. Wang Y, Yin H, Li J, et al. Amelioration of beta-amyloid-induced cognitive dysfunction and hippocampal axon degeneration by curcumin is associated with suppression of CRMP-2 hyperphosphorylation. Neurosci Lett.2013;557 Pt B:112-117.
24. Thiyagarajan M, Sharma SS.Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats.Life Sci. 2004;74(8):969-985.
25. Deng X, Wang Y, Chou J, et al.Methamphetamine causes widespread apoptosis in the mouse brain: evidence from using an improved TUNEL histochemical method.Brain Res Mol Brain Res. 2001;93(1):64-69.
26. Sclip A, Arnaboldi A, Colombo I, et al.Soluble Aβ oligomer-induced synaptopathy: c-Jun N-terminal kinase’s role.J Mol Cell Biol. 2013; 5(4):277-279.
27. Yin HL, Wang YL, Li JF, et al.Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats.Genet Mol Res. 2014;13(1):2039-2047.
28. Modi KK, Jana A, Ghosh S, et al.A physically-modified saline suppresses neuronal apoptosis, attenuates tau phosphorylation and protects memory in an animal model of Alzheimer’s disease.PLoS One. 2014;9(8):e103606.
29. Cervia D, Perrotta C, Moscheni C, et al.Nitric oxide and sphingolipids control apoptosis and autophagy with a significant impact on Alzheimer’s disease.J Biol Regul Homeost Agents. 2013;27(2 Suppl):11-22.
30. Song J, Park KA, Lee WT, Lee JE.Apoptosis signal regulating kinase 1 (ASK1): potential as a therapeutic target for Alzheimer’s disease.Int J Mol Sci. 2014;15(2):2119-2129.
31. Thinnes FP.Apoptogenic interactions of plasmalemmal type-1 VDAC and Abeta peptides via GxxxG motifs induce Alzheimer’s disease - a basic model of apoptosis?Wien Med Wochenschr. 2011;161(9-10):274-276.
32. Bertoni-Freddari C, Fattoretti P, Casoli T, et al.Neuronal apoptosis in Alzheimer’s disease: the role of age-related mitochondrial metabolic competence.Ann N Y Acad Sci. 2009;1171:18-24.
33. Genc S, Egrilmez MY, Yaka E, et al.TNF-related apoptosis-inducing ligand level in Alzheimer’s disease.Neurol Sci. 2009;30(3):263-267.
34. Ahmed T, Gilani AH.A comparative study of curcuminoids to measure their effect on inflammatory and apoptotic gene expression in an Abeta plus ibotenic acid-infused rat model of Alzheimer’s disease.Brain Res. 2011;1400:1-18.
35. Mulik RS, Monkkonen J, Juvonen RO, et al.ApoE3 mediated poly (butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model.Mol Pharm. 2010;7(3):815-825.
36. Pan R, Qiu S, Lu DX, et al.Curcumin improves learning and memory ability and its neuroprotective mechanism in mice.Chin Med J (Engl). 2008;121(9):832-839.
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