Neuroprotective role of curcumin on the hippocampus against the structural and serological alterations of streptozotocin-induced diabetes in sprague dawely rats

Document Type: Original Article

Authors

1 Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Egypt

2 Department of Medical Biochemistry, Faculty of Medicine (New Damietta), Al Azhar University, Egypt & Department of Clinical Laboratories, College of Applied Medical Sciences, Taif University, KSA

Abstract

Objective(s): Diabetes mellitus causes impaired memory and cognitive functions. The hippocampus plays a key role in memory and learning. Curcumin attenuates diabetic nephropathy in vivo. Curcumin has shown a neurogenic effect and cognition-enhancing potential in aged rats. The aim of this study is to evaluate the possible protective role of curcumin on the histological and serologicalchanges of the hippocampus in diabetic rats.
Materials and Methods: Forty albino rats were divided into four groups, ten rats each. Group 1 control rats, group 2 rats received curcumin orally (200 mg/kg/day for six weeks), group 3 rats were injected intraperitoneally with streptozotocin (STZ) (100 mg/kg, single dose), group 4 received a single injection of STZ and received curcumin orally for six weeks. Paraffin sections of hippocampus were prepared and stained with hematoxylin and eosin stain, and immnunohistochemical staining for GFAP and caspase-3. Morphometrical and statistical analyses were performed. Glycemic status and parameters of oxidative stress was measured.
Results: Examination of hippocampus of diabetic rats showed disorganization of small pyramidal cells in CA1, many cellular losses in the pyramidal cells of CA3, many degenerated granule cells in the dentate gyrus. GFAP positive astrocyte and caspase-3 positive neuron counts were significantly increased.  There were significant serum glucose elevation and significant lowered levels of oxidative stress parameters as compared to control rats. Curcumin administration improved the structural and serological alterationsof the hippocampuswith significant reduction in serum glucose level.
Conclusion: Curcumin ameliorates the deterious effect of diabetes on the hippocampus through its antioxidant, antiapoptotic and anti-inflammatory efficacies.

Keywords


1. American Diabetes Association (2012). Diagnosis and classification of diabetes mellitus. Diabetes Care 2012; 33:S62–S69.

2. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes:  estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27:1047-1053.

3. Selvarajah D, Wilkinson ID, Davies J, Gandhi R, Tesfaye S. Central nervous system involvement in diabetic neuropathy. Curr Diab Rep 2011; 11:310-322.

4. Nagayach A, Patro N, Patro I. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Front Cell Neurosci 2014; 8:355.

5. Saravia F, Revsin Y, Lux-Lantos V, Beauquis J, Homo-Delarche F, De Nicola, AF. Oestradiol restores cell proliferation in dentate gyrus and subventricular zone of streptozotocin-diabetic mice. J Neuroendo-crinol 2004; 16:704–710.

6. Greenwood CE, Winocur G. High–fat diets, insulin resistance and declining cognitive function. Neurobiol Aging 2005; 26:42–45.

7. Biessels GJ, Kamal A, Urban IJ, Spruijt BM, Erkelens DW, Gispen WH. Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment. Brain Res 1998; 800:125-135.

8. Kiernan JA. BARR'S The Human Nervous System: An anatomical viewpoint. 9th ed. Lippincott Williams & Wilkins; 2009.p.158- 171.

9. Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ Med J 2012; 12:5-18.

10. Graves DT, Liu R, Oates TW. Diabetes-enhanced inflammation and apoptosis: impact on periodontal pathosis. Periodontol 2007; 45:128-137.

11. Ugwuja EI, Nwibo AN, Ugwu NC, Aloke C. Effect of aqueous extract of spices mixture containing curry, garlic and ginger on plasma glucose and lipid in alloxan-induced diabetic rats. Pak J Nutr 2010; 9:1131-1135.

12. Perez-Torres I, Ruiz-Ramirez A, Banos G, El-Hafidi M. “Hibiscus sabdariffa Linnaeus (Malvaceae), curcumin and resveratrol as alternative medicinal agents against metabolic syndrome.” Cardiovasc Hematol Agents Med Chem 2013; 11:25-37.

13. Sun LN, Liu XC, Chen XJ, Guan GJ, Liu G. Curcumin attenuates high glucose-induced podocyte apoptosis by regulating functional connections between caveolin-1 phosphorylation and ROS. Acta Pharmacol Sin 2016; 37:645-655.

14. Dong S, Zeng Q, Mitchell ES, Xiu J, Duan Y, Li C, et al. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity. PLoS One 2012; 7:e31211.

15. Li Y, Li J, Li S, Li Y, Wang X, Liu B, et al. Curcumin attenuates glutamate neurotoxicity in the hippo-campus by suppression of ER stress associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK. Toxicol Appl Pharmacol 2015; 286:53-63.

16. Niu Y, Liang S, Wang X. Abnormal change in body weight and non-fasting blood glucose levels of mouse strain C57BL/6J in generating type 2 diabetes model. Zool Res 2007; 28:507-510.

17. Farombi EO, Shrotriya S, Na HK, Kim SH, Surh YJ. Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1. Food Chem Toxicol 2008; 46:1279-1287.

18. Bancroft JD, Gamble M. “Theory and Practice of Histological Techniques”. 5th ed. New York: Churchill Livingstone; 2002.p. 593-620.

19. Zarnescu O, Brehar FM, Chivu M, Ciurea AV. Immunohistochemical localization of caspase-3, caspase-9 and Bax in U87 glioblastoma xenografts. J Mol Histol 2008; 39:561- 569.

20. Aebi H. “Catalase in vitro,” Methods in enzymology. 1984; 105:121–126.

21. Geraghty P, Hardigan AA, Wallace AM, Mirochnitchenko O, Thankachen J, Arellanos L, et al. The glutathione peroxidase 1-protein tyrosine phosphatase 1B-protein phosphatase 2A axis. A key determinant of airway inflammation and alveolar destruction. Am J Respir Cell Mol Biol 2013; 49:721–730.

22. Sun Y, Oberley LW, Li Y. “A simple method for clinical assay of superoxide dismutase,”. Clin Chem 1988; 34:497–500.

23. Ellman M. A spectrophotometric method for determination of reduced glutathione in tissues. Anal Biochem 1959 74:214–226. 27. Aebi HE. Catalase. In: Bergmeyer HU, ed. Methods of enzymatic analysis. New York: Academic Press; 1983.p. 3:276–86.

24. Ho N, Sommers MS, Lucki I. Effects of diabetes on hippocampal neurogenesis: Links to Cognition and Depression. Neurosci Biobehav Rev 2013; 37:1346–1362.

25. Amin SN, Younan SM, Youssef MF, Rashed LA, Mohamady I. A histological and functional study on hippocampal formation of normal and diabetic rats.  F1000Res 2013; 2:151-173.

26. Zhou J, Wang L, Ling S, Zhang X. Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats. Exp Neurol 2007; 206:201-208.

27. Pamidi N, Satheesha Nayak BN. Effect of streptozotocin induced diabetes on rat hippocampus. Bratisl Lek Listy 2012; 113:583-588.

28. Vincent AM, Brownlee M, Russell JW. Oxidative stress and programmed cell death in diabetic neuropathy. Ann N Y Acad Sci. 2002; 959:368-383.

29. Zhao CH, Liu HQ, Cao R, Ji AL, Zhang L, Wang F, et al. Effects of dietary fish oil on learning function and apoptosis of hippocampal pyramidal neurons in streptozotocin-diabetic rats. Brain Res 2012; 1457: 33–43.

30. Russell JW, Sullivan KA, Windebank AJ, Herrmann DN, Feldman EL. Neurons undergo apoptosis in animal and cell culture models of diabetes. Neurobiol  Dis 1999; 6:347–363.

31. Ceriello A. New insights on oxidative stress and diabetic complications may lead to a ‘causal' antioxidant therapy. Diabetes Care 2003; 26:1589-1596.

32. Klein JP, Waxman SG. The brain in diabetes: molecular changes in neurons and their implications for end-organ damage. Lancet Neurol 2003; 2:548–554.

33. Li ZG, Zhang W, Grunberger G, Sima AA. Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res 2002; 946:221-231.

34. Baydas G, Reiter RJ, Yasar A, Tuzcu M, Akdemir I, Nedzvetskii VS. Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats. Free Radic Biol Med 2003; 35:797-804.

35. Saravia FE, Revsin Y, Gonzalez Deniselle MC, Gonzalez SL, Roig P, Lima A,  et al. Increased astrocyte reactivity in the hippocampus of murine models of type 1 diabetes: the nonobese diabetic (NOD) and streptozotocin-treated mice. Brain Res 2002; 957:345-353.

36. Dennis JC, Coleman ES, Swyers SE, Moody SW, Wright JC, Judd R, et al. Changes in mitotic rate and GFAP expression in the primary olfactory axis of streptozotocin-induced diabetic rats. J Neurocytol. 2005; 34(1-2):3-10.

37. Afsari ZH, Renno WM, Abd-El-Basset E. Alteration of glial fibrillary acidic proteins immunoreactivity in astrocytes of the spinal cord diabetic rats. Anat Rec 2008; 291:390-399.

38. Barber AJ, Antonetti DA, Gardner TW. Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. Invest Ophthalmol Vis Sci 2000; 41:3561–3568.

39. Coleman E, Judd R, Hoe L, Dennis J, Posner P. Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS. Glia 2004; 48:166–178.

40. Brown GC, Neher JJ. Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Mol Neurobiol.2010; 41:242-247.

41. Mahesh T, Sri Balasubashini MM, Menon VP. Photo-irradiated curcumin supplementation in streptozotocin-induced diabetic rats: effect on lipid peroxidation. Therapie 2010; 59:639–644.

42. Chougala MB, Bhaskar JJ, Rajan MG, Salimath PV. Effect of curcumin and quercetin on lysosomal enzyme activities in streptozotocin-induced diabetic rats. Clin Nutr 2012; 31:749-755.

43. Kamel R, Hashim A, Ali S. Palliative effect of curcumin ON STZ-induced diabetes in rats. Int J Pharm Sci 2014; 1491:558-563.

44. Yu W, Wu J, Cai F, Xiang J, Zha W, Fan D, et al. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLoS One 2012; 7: e52013.

45. Kim SJ, Son TG, Park HR, Park M, Kim MS, Kim HS, et al. Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem 2008; 2008:14497-14505.

46. Zuo ZF, Zhang Q, Liu XZ. Protective effects of curcumin on retinal Müller cell in early diabetic rats. Int J Ophthalmol.2013, 6: 422–424.

47.  Borra SK, Gurumurthy P, Mahendra M, Jayamathi KM, Cherian CN, Ram C. “Antioxidant and free radical scavenging activity of curcumin determined by using different in vitro and ex vivo models,” J Med Plants Res 2013; 7:2680–2690.

48.  El-Bahr SM. Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats.BMC Complement Altern Med 2013; 13:368.