Exp Clin Endocrinol Diabetes 2014; 122(10): 615-619
DOI: 10.1055/s-0034-1385925
Article
© Georg Thieme Verlag KG Stuttgart · New York

Relationship between the Level of Hippocampal Leptin Receptor Gene Expression and Learning Performance in Diabetic Rats

C. Demirel
1   Department of Biophysics, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
,
S. O. Balcı
2   Department of Medical Biology, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
,
H. Korkmaz
3   Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
,
E. Akarsu
3   Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
› Author Affiliations
Further Information

Publication History

received 13 May 2014
first decision 15 July 2014

accepted 23 July 2014

Publication Date:
07 November 2014 (online)

Abstract

Diabetes mellitus may be associated with impaired cognitive function. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. Leptin that is a peptide hormone, acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor mediated transmission. The aim of the present study is to investigate possible relationship between the hippocampal leptin receptor gene expression and learning performance in streptozotocin (STZ) induced diabetic rats. In this study was conducted on a total of 40 Winstar albino female rats, including a control group consisting of 20 rats and experimental group comprising of 20 rats in which diabetes was induced by means of STZ administration. Leptin receptor gene expression was detected in hippocampal samples by using real time-PCR. According to the evaluation, the learning performance of rats with induced diabetes was found to be same throughout the first 3 days after STZ in comparison to the control group rats. End of the 45 days the learning performance of the control group was found to be better than the diabetic group (p<0.05). Hipocampal leptin receptor expression was found lower in diabetic group than the control group (p<0.05). The results provide evidence that leptin receptor gene may related to learning performance in diabetic rats. Further, detailed studies are needed to address the exact role of leptin and related molecules in learning performance.

 
  • References

  • 1 Ates M, Dayi A, Kiray M et al. Anxiety- and depression-like behavior are correlated with leptin and leptin receptor expression in prefrontal cortex of streptozotocin-induced diabetic rats. Biotech Histochem 2014; 89: 161-171
  • 3 Baptista FI, Pinto MJ, Elvas F et al. Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus. PLoS One 2013; 8: e65515
  • 5 Bliss TV, Collingridge GL. A Synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361: 31-39
  • 7 Biessels GJ, Kamal A, Urban IJ et al. Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment. Brain Res 1998; 800: 125-135
  • 9 Collingridge GL, Kehl SJ, McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol 1983; 334: 33-46
  • 11 Convit A. Links between cognitive impairment in insulin resistance: an explanatory model. Neurobiol Aging 2005; 26: 31-35
  • 13 Couce ME, Burguera B, Parisi JE et al. Localization of leptin receptor in the human brain. Neuroendocrinology 1997; 66: 145-150
  • 15 Derakhshan F, Toth C. Insulin and the brain. Curr Diabetes Rev 2013; 9: 102-116
  • 17 Farr SA, Banks WA, Morley JE. Effects of leptin on memory processing. Peptides 2006; 27: 1420-1425
  • 19 Harvey J, McKay NG, Walker KS et al. Essential role of phosphoinositide 3-kinase in leptin-induced K (ATP) channel activation in the rat CRI-G1insulinoma cell line. J Biol Chem 2000; 275: 4660-4669
  • 21 Harvey J. Leptin: a diverse regulator of neuronal function. J Neurochem 2007; 100: 307-313
  • 23 Harvey J, Shanley LJ, O’Malley D et al. Leptin: a potential cognitive enhancer?. Biochem Soc Trans 2005; 33: 1029-1032
  • 25 Harvey J. Leptin regulation of neuronal morphology and hippocampal synaptic function. Front Synaptic Neurosci 2013; 5: 3
  • 27 Huang CC, Lee CC, Hsu KS. The Role of Insulin Receptor Signaling in Synaptic Plasticity and Cognitive Function. Chang Gung Med J 2010; 33: 115-125
  • 29 Kodl CT, Seaquist ER. Cognitive Dysfunction and Diabetes Mellitus. Endocr Rev 2008; 29: 494-511
  • 31 Liu L, Brown JC, Webster WW et al. Insulin potentiates N- methyl-D-aspartate receptor activity in Xenopus oocytes and rat hippocampus. Neurosci Lett 1995; 192: 5-8
  • 33 Li XL, Aou S, Oomura Y et al. Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents. Neuroscience 2002; 113: 607-615
  • 35 Malenka RC. Synaptic plasticity in the hippocampus: LTP and LTD. Cell 1994; 78: 535-538
  • 37 Man HY, Lin JW, Ju WH et al. Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. Neuron 2000; 25: 649-662
  • 39 McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive dysfunction. Lancet 2012; 379: 2291-2299
  • 41 Moult PR, Cross A, Santos SD et al. Leptin regulates AMPA receptor trafficking via PTEN inhibition. J Neurosci 2010; 30: 4088-4101
  • 43 Munshi M, Grande L, Hayes M et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care 2006; 29: 1794-1799
  • 45 Passafaro M, Piëch V, Sheng M. Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nat Neurosci 2001; 4: 917-926
  • 47 Reagan LP. Insulin signaling effects on memory and mood. Curr Opin Pharmacol 2007; 7: 633-637
  • 49 Reagan LP. Neuronal insulin signal transduction mechanisms in diabetes phenotypes. Neurobiol Aging 2005; 1: 56-59
  • 51 Schwartz MW, Figlewicz DP, Baskin DG et al. Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev 1992; 13: 387-414
  • 53 Shapiro M. Plasticity, hippocampal place cells, and cognitive maps. Arch Neurol 2001; 58: 874-881
  • 55 Shanley LJ, Irving AJ, Harvey J. Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity. J Neurosci 2001; 21: RC186
  • 57 Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87: 4-14
  • 59 Skeberdis VA, Lan J, Zheng X et al. Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci 2001; 98: 3561-3566
  • 61 Spanswick D, Smith MA, Mirshamsi S et al. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 2000; 3: 757-758
  • 63 Wayner MJ, Armstrong DL, Phelix CF et al. Orexin-A (Hypocretin-1) and leptin enhance LTP in the dentate gyrus of rats in vivo. Peptides 2004; 25: 991-996
  • 65 Wessels AM, Scheltens P, Barkhof F et al. Hyperglycaemia as a determinant of cognitive decline in patients with type 1 diabetes. Eur J Pharmacol 2008; 585: 88-96