Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats

Yıl 2016, Cilt: 33 Sayı: 1, 102 - 107, 01.01.2016

Mohsen Ghasemi Bamdad Zendehbad Hoda Zabihi Mousa Al Reza Hadjzadeh Parichehr Hayatdavoudi

Öz

Background: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. Aims: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. Study Design: Animal experimentation. Methods: The rats were divided into three groups: 1- control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. Results: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. Conclusion: Leptin can exert positive effects on memory impairments in diabetic rats.

Anahtar Kelimeler

Leptin, spatial memory, streptozotocin

Kaynakça

• 1. Huber JD, Vangilder RL, Houser KA, Jason D, Kimberly A. Streptozotocin-induced diabetes progressively increases bloodbrain barrier permeability in specific brain regions in rats. Am J Physiol Heart Circ Physiol 2006;291:2660-8. [CrossRef]
• 2. McNay EC, Recknagel AK. Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes. Neurobiol Learn Mem 2011;96:432-42. [CrossRef]
• 3. Ryan CM, Freed MI, Rood JA, Cobitz AR, Waterhouse BR, Strachan MW. Improving Metabolic Control Leads to Better Working Memory in Adults With Type 2 Diabetes. Diabetes Care 2006;29:345-51. [CrossRef]
• 4. Ceddia RB, Koistinen HA, Zierath JR, Sweeney G. Analysis of paradoxical observations on the association between leptin and insulin resistance. FASEB J 2002;16:1163-76. [CrossRef]
• 5. Havel PJ, Uriu-hare JY, Liu T, Stanhope KL, Stern JS, Keen CL, et al. Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats : reversal by insulin. Am J Physiol 1998;274:1482-91.
• 6. Li X, Aou S, Oomura Y, Hori N, Fukunaga K, Hori T. Impairment of Long-Term Potentiation and spatial memory in Leptin receptor-deficient rodents. Neuroscience 2002;113:607-15. [CrossRef]
• 7. Farr SA, Banks WA, Morley JE. Effects of leptin on memory processing. Peptides 2006;27:1420-5. [CrossRef]
• 8. Oomura Y, Hori N, Shiraishi T, Fukunaga K, Takeda H, Tsuji M, et al. Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats. Peptides 2006;27:2738-49. [CrossRef]
• 9. Gisou M, Soheila R, Nasser N. Evaluation of the effect of intrahippocampal injection of leptin on spatial memory. African J Pharm Pharmacol 2009;3:443-8.
• 10. Beccano-Kelly D, Harvey J. Leptin : A Novel Therapeutic Target in Alzheimer’s Disease ? Int Journal of Alzheimers Dis 2012;2012:594137.
• 11. Rasi S, Mohaddes G, Naghdi N, Ilkhani MVH. Evaluation of the Effect of Peripheral Injection of Leptin on Spatial Memory. Int J Neurol 2006;8:1-7.Available from www.ISPUB.COM/IJN.
• 12. Ding Y, Qiao A, Wang Z, Goodwin JS, Lee E, Block ML, et al. Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer’s disease transgenic mouse model. J Neurosci 2008;28:11622-34. [CrossRef]
• 13. Palou March M, Tobaruela Arbona A. Univ de les Illes Balears. Use of leptin in the treatment of alterations in food habits. Spain, EP2005967A1. 2008.
• 14. Bibak B, Khalili M, Rajaei Z, Soukhtanloo M, Hadjzadeh M, Hayatdavoudi P. Effects of melatonin on biochemical factors and food and water consumption in diabetic rats. Adv Biomed Res 2014;3:1-7.
• 15. Biessels G, Kamal A, Ramakers GM, Urban IJ, Spruijt BM, Erkelens DW, et al. Place Learning and Hippocampal Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats. Diabetes 1996;45:1259-66. [CrossRef]
• 16. Baydas G, Nedzvetskii VS, Nerush PA. Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin-induced diabetes mellitus. Life Sci 2003;73:1907-16. [CrossRef]
• 17. Babri S, Azami SH, Mohaddes G. Effect of Acute Administration of loganin on Spatial Memory in Diabetic Male Rats. Adv Pharm Bull 2013;3:91-5.
• 18. Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Corrêa M, et al. Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol 2009;610:42-8. [CrossRef]
• 19. Ravishankar R, Sanjiva DK. Effects of Duration of Diabetes on Behavioural and Cognitive Parameters in Streptozotocin-Induced Juvenile Diabetic Rats. Malays J Med Sci 2011;18:26-31.
• 20. Marwarha G, Prasanthi JRP, Schommer J, Dasari B, Ghribi O. Molecular interplay between leptin , insulin-like growth factor-1 , and b-amyloid in organotypic slices from rabbit hippocampus. Mol Neurodegener 2011;1:1-18. [CrossRef]
• 21. Greco SJ, Sarkar S, Johnston JM, Tezapsidis N. Leptin regulates Tau phosphorylation and Amyloid through AMPK in Neuronal Cells. Biochem Biophys Res Commun 2009;380:98-104. [CrossRef]
• 22. Catal V, Rodr A, Javier G, Fortu A. Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms. Mediators Inflamm 2010;2010:1-10.
• 23. Harvey J, Solovyova N, Irving A. Leptin and its role in hippocampal synaptic plasticity. Prog Lip Res 2006;45:369-78. [CrossRef]
• 24. Karakaş A, Coşkun H, Kizilkaya FU. Memory-enhancing effects of the leptin hormone in Wistar albino rats : sex and generation differences. Turk J Biol 2013;37:222-9.
• 25. Morrison CD. Leptin signaling in brain : A link between nutrition and cognition ? Biochim Biophys Acta 2009;1792:401-8.
• 26. Patel BK, Koenig JI, Kaplan LM, Hooi SC. Increase in plasma leptin and lep mRNA concentrations byfood intake is dependent on insulin. Metabolism 1998;47:603-7. [CrossRef]
• 27. Oomura Y, Aou S, Fukunaga K. Prandial increase of leptin in the brain activates spatial learning and memory. Pathophysiology 2010;17:119-27. [CrossRef]
• 28. Garza JC, Guo M, Zhang W, Lu XY. Leptin restores adult hippocampal neurogenesis suppressed by chronic unpredictable stress and reverses glucocorticoid-induced inhibition of GSK3β/βcatenin signaling. Mol Psychiatry 2012;17:790-808. [CrossRef]
• 29. Foster TC. Role of estrogen receptor alpha and beta expression and signaling on cognitive function during aging. Hippocampus 2013;22:656-69. [CrossRef]
• 30. Liu E, Samad F, Mueller BM. Local adipocytes enable estrogendependent breast cancer growth Role of leptin and aromatase. Adipocyte 2013;2:165-9. [CrossRef]
• 31. Witty CF, Foster TC, Semple-Rowland SL, Daniel JM. Increasing Hippocampal Estrogen Receptor Alpha Levels via Viral Vectors Increases MAP Kinase Activation and Enhances Memory in Aging Rats in the Absence of Ovarian Estrogens. PLoS One 2012;7:1-10. [CrossRef]
• 32. Li B, Wang LU, Liu Y, Chen Y, Zhang Z, Zhang J. Jujube promotes learning and memory in a rat model by increasing estrogen levels in the blood and nitric oxide and acetylcholine levels in the brain. Exp Ther Med 2013;5:1755-9. [CrossRef]
• 33. Mastronardi CA, Yu WH, Mccann SM. Resting and circadian release of nitric oxide is controlled by leptin in male rats. Proc Natl Acad Sci U S A 2002;99:5721-6. [CrossRef]
• 34. Hacioglu A, Algin C, Pasaoglu O, Pasaoglu E, Kanbak G. Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine. BMC Gastroenterol 2005;5:1-7. [CrossRef]