Allicin attenuates tunicamycin-induced cognitive deficits in rats via its synaptic plasticity regulatory activity

Document Type: Original Article

Authors

1 Institute of Medicine, Medical Research Center, Jishou University, Hunan, China

2 Jishou University First Affiliated Hospital, Jishou University, Hunan, China

3 College of Chemistry and Chemical Engineering, Jishou University, Hunan, China

Abstract

Objective(s): To illuminate the functional effects of allicin on rats with cognitive deficits induced by tunicamycin (TM) and the molecular mechanism of this process.
Materials and Methods: 200–250 g male SD rats were divided into three groups at random: control group (n=12), TM group (5 μl, 50 μM, i.c.v, n=12), and allicin treatment group (180 mg/kg/d with chow diet, n=12). After 16 weeks of allicin treatment, the learning ability and memory were tested using novel object recognition (NOR) testing on rats with 72 hr TM treatment (5 μl, 50 μM, i.c.v); meanwhile, the variation of field excitatory postsynaptic potential (fEPSP) in the Schaffer Collateral (SC)-CA1 synapse was detected by extracellular electrophysiological recordings and the morphology of dendritic spine was observed by Golgi staining as well as detecting several synaptic plasticity-related proteins by Western blot.
Results: The density of dendritic spine was increased significantly in allicin-treated groups and the correspondence slope of fEPSP in TM-induced cognitive deficits group was enhanced and expression of synaptophysin and glutamate receptor-1(GluR1) in hippocampal neurons was up-regulated.
Conclusion: The results indicate that allicin plays an important role in synaptic plasticity regulation. These finding showed that allicin could be used as a pharmacologic treatment in TM-induced cognitive deficits.

Keywords


1. Fonseca SG, Burcin M, Gromada J, Urano F. Endoplasmic reticulum stress in β-cells and development of diabetes. Curr Opin Pharmacol 2009; 9:763-770.

2. Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol 2011; 54:795-809.

3. Dandekar A, Mendez R, Zhang K. Cross talk between ER stress, oxidative stress, and inflammation in health and disease. Methods Mol Biol 2015; 1292:205-214. 

4. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 2011; 334:1081-1086.

5. Zhu YF, Li XH, Yuan ZP, Li CY, Tian RB, Jia W. Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway. Eur J Pharmacol 2015; 762:239-246.

6. Roy S, Zhang B, Lee V MY, Trojanowski JQ. Axonal trans-port defects: a common theme in neurodegenerative diseases. Acta Neuropathol 2005; 109:5-113.

7. Tampellini D. Synaptic activity and Alzheimer's disease: a critical update. FrontNeurosci 2015; 9:423.

8. Borlinghaus J, Albrecht F, Gruhlke M, Nwachukwu I, Slusarenko A. Allicin: chemistry and biological properties. Molecules 2014;19:12591-12618.

9. Lee KJ, Moussa CE, Lee Y, Sung Y, Howell BW, Turner RS, et al. Beta amyloid-independent role of amyloid precursor protein in generation and maintenance of dendritic spines. Neuroscience 2010; 169:344-356.

10. Berberich S, Jensen V, Hvalby Ø, Seeburg PH, Köhr G. The role of NMDAR subtypes and charge transfer during hippocampal LTP induction. Neuropharmaco-logy 2007; 52:77-86.

11. Gu X, Wu H, Fu P. Allicin attenuates inflammation and suppresses HLA-B27 protein expression in ankylosing spondylitis mice. Bio Med Res Int 2013; 6.

12. JiangW, Huang Y, Wang JP, Yu XY, Zhang LY. The synergistic anticancer effect of artesunate combined with allicin in osteosarcoma cell line in vitro and in vivo. Asian Pac J Cancer Prev 2013; 14:4615-4619.

13. Xu L, Yu J, Zhai D, Zhang D, Shen W, Bai L, et al. Role of JNKactivation andmitochondrial Bax translocation in allicin-induced apoptosis in human ovarian cancer SKOV3 cells. Evid Based Complement Alternat Med 2014; 2014:378684.

14. Zhang L, Wang E, Chen F, Yan H, Yuan Y. Potential protective effects of oral administration of allicin on acrylamideinduced toxicity in male mice. Food Funct 2013; 4:1229-1236.

15. Li XH, Li CY, Xiang ZG, Hu JJ, Lu JM, Tian RB, et al. Allicin ameliorates cardiac hypertrophy and fibrosis through enhancing of Nrf2 antioxidant signaling pathways. Cardiovasc Drugs Ther 2012; 26:457-465.

16. Li XH, Li CY, Lu JM, Tian RB, Wei J. Allicin ameliorates cognitive deficits ageing-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Neurosci Lett 2012; 514:46-50.

17. Lissiman E, Bhasale AL, Cohen M. Garlic for the common cold. Cochrane Database Syst Rev 2009; 8:CD006206.

18. Yang EJ, Yim EY, Song G, Kim GO, Hyun CG. Inhibition of nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages by Jeju plant extracts. Interdiscip Toxicol 2009; 2:245-249.

19. Squire LR, Wixted JT, Clark RE . Recognition memory and the medial temporal lobe: A new perspective. Nat Rev Neurosci2007;8:872–883.

20. Broadbent NJ, Squire LR, Clark RE . Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci U S A 2004; 101:14515-14520.

21. Clark RE, Zola SM, Squire LR. Impaired recognition memory in rats after damage to the hippocampus.J Neurosci 2000; 20:8853-8860.

22. Bevins RA, Besheer J. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study “recognition memory”. Nat Protoc 2006; 1:1306-1311.

23. Maiti P, Manna J, Ilavazhagan G, Rossignol J, Dunbar GL. Molecular regulation of dendritic spine dynamics and their potential impact on synaptic plasticity and neurological diseases. Neurosci Biobehav Rev 2015; 59:208-237.

24. Wang W, Wang F, Yang YJ, Hu ZL, Long LH, Fu H, et al. The flavonoid baicalein promotes NMDA receptor-
dependent long-term potentiation and enhances memory. Br J Pharmacol 2011 Mar;162:1364-1379.

25. Han T, Qin Y, Mou C, Wang M, Jiang M, Liu B. Seizure induced synaptic plasticity alteration in hippocampus is mediated by IL-1β receptor through PI3K/Akt pathway. Am J Transl Res 2016; 8:4499-4509.

25. Mark LP, Prost RW, Ulmer JL, Smith MM, Daniels DL, Strottmann JM, et al. Pictorial review of glutamate excitotoxicity: fundamental concepts for neuroimaging. Am J Neuroradiol 2001; 22:1813–1824.

26. Lei M, Xu H, Li Z, Wang Z, O'Malley TT, Zhang D, et al. Soluble Aβ oligomers impair hippocampal LTP by disrupting glutamatergic/GABAergic balance. Neurobiol Dis 2015; 85:111-121.

27. Mancini M, Ghiglieri V, Bagetta V, Pendolino V, Vannelli A, Cacace F, et al. Memantine alters striatal plasticity inducing a shift of synaptic responses toward long-term depression. Neuropharmacology 2015; 101:341-350.

28. Ribeiro FM, Vieira LB, Pires RG, Olmo RP, Ferguson SS. Metabotropic glutamate receptors and neurodegenerative diseases. Pharmacol Res 2016; 115:179-191.

29. Latif-Hernandez A, Faldini E, Ahmed T, Balschun D. Separate ionotropic and metabotropic glutamate receptor functions in depotentiation vs. LTP: A distinct role for group1 mGluR subtypes and NMDARs. Front Cell Neurosci 2016; 10:252.

30. Wang S, Zhang J, Sheng T, Lu W, Miao D. Hippocampal ischemia causes deficits in local field potential and synaptic plasticity. J Biomed Res 2015; 29:370-379.

31. Chalecka-Franaszek E, Chuang DM. Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci U S A 1999; 96: 8745-8750.

32. Kantamneni S. Cross-talk and regulation between glutamate and GABAB receptors. Front Cell Neurosci 2015; 9:135.