Increased Expression of Phosphorylated Smad2 and Smad3 in the Hippocampus of Streptozotocin-induced Diabetic Rats

Y. Bao; L. Jiang; Y.-Q. Shi; J.-J. Zou; Y. Zhao; Z.-M. Liu

doi:10.1055/s-0029-1225610

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2010; 118(1): 47-50
DOI: 10.1055/s-0029-1225610

Article

Increased Expression of Phosphorylated Smad2 and Smad3 in the Hippocampus of Streptozotocin-induced Diabetic Rats

Y. Bao¹ [*] , L. Jiang² [*] , Y.-Q. Shi¹ , J.-J. Zou¹ , Y. Zhao³ , Z.-M. Liu¹

¹Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai, China
²Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China
³Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China

Abstract

Activation of the Smad signalling pathway has been implicated in the pathological process of diabetic associated complications. The current study was designed to see whether Smad signalling was activated in the hippocampus of streptozotocin-induced diabetic rats. Compared with vehicle-treated controls, immunoblot analysis of hippocampal extracts showed that phosphorylated Smad2 was upregulated at 8 weeks post streptozotocin induction (p<0.01), and phosphorylated Smad3 protein was upregulated at 4 and 8 weeks post streptozotocin induction (p<0.01) in streptozotocin-induced diabetic rats. In addition, immunofluorescence labelling assay showed that the percentage of pSmad2 immunoreactive astrocytes increased significantly in CA1, CA3 and dentate gyrus region (p<0.01), and pSmad3 immunoreactive astrocytes increased significantly in CA1 region (p<0.01) and in CA3 and dentate gyrus region (p<0.05) of the hippocampus in diabetic rats. These data indicate that Smad signalling is enhanced in hippocampal astrocytes of diabetic rats, and may thereby represent a clue to explore its exact role in the development of diabetic encephalopathy.

Key words

Smad - diabetic encephalopathy - hippocampus - astrocyte

Full Text

References

1 Artola A, Kamal A, Ramakers GM. et al . Synaptic plasticity in the diabetic brain: Advanced aging?. Prog Brain Res. 2002; 138 305-314
2 Arvanitakis Z, Wilson RS, Bievias JL. et al . Diabetes mellitus and risk of Alzheimer's disease and decline in cognitive function. Arch Neurol. 2004; 61 661-666
3 Bailes BK. Diabetes mellitus and its chronic complications. AORN J. 2002; 76 266-276 278-282 quiz 283-286
4 Bansal V, Kalita J, Misra UK. Diabetic neuropathy. Postgrad Med J. 2006; 82 95-100
5 Baydas G, Nedzvetskii VS, Tuzcu M. et al . Increase of glial fibrillary acidic protein and S-100B in hippocampus and cortex of diabetic rats: effects of vitamin E. Eur J Pharmacol. 2003; 462 67-71
6 Brands AM, Biessels GJ, Haan de EH. et al . The effects of type 1 diabetes on cognitive performance. Diabetes Care. 2005; 28 726-735
7 Docagne F, Gabriel C, Lebeurrier N. et al . Sp1 and Smad transcription factors co-operate to mediate TGF-beta-dependent activation of amyloid-beta precursor protein gene transcription. Biochem J. 2004; 383 393-399
8 Gispen WH, Biessels GJ. Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci. 2000; 23 542-549
9 Gordon KJ, Blobe GC. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta. 2008; 1782 197-228
10 Gray W, Patel AJ. Regulation of β-amyloid precursor protein isoform mRNA's by transforming growth factor-β1 and interleukin-1 β in astrocytes. Mol Brain Res. 1993; 19 251-256
11 Greene DA, Stevens MJ, Obrosova I. et al . Glucose-induced oxidative stress and programmed cell death in diabetic neuropathy. Eur J Pharmacol. 1999; 375 217-223
12 Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997; 390 465-471
13 Li JH, Huang XR, Zhu HJ. et al . Advanced glycation end products activate Smad signaling via TGF-beta-dependent and independent mechanisms: implications for diabetic renal and vascular disease. FASEB J. 2004; 18 176-178
14 Li ZG, Zhang W, Grunberger G. et al . Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res. 2002; 946 212-231
15 Li ZG, Zhang W, Sima AA. Alzheimer-like changes in rat models of spontaneous diabetes. Diabetes. 2007; 56 1817-1824
16 Mijnhout GS, Scheltens P, Diamant M. et al . Diabetic encephalopathy: a concept in need of a definition. Diabetologia. 2006; 49 1447-1448
17 Piotrowski P, Wierzbicka K, Smiatek M. Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischemia treated with antioxidants. Folia Neuropathol. 2001; 39 147-154
18 Revsin Y, Saravia F, Roig P. et al . Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes. Brain Res. 2005; 103 822-831
19 Saravia FE, Revsin Y, Gonzalez Deniselle MC. 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
20 Wyss-Coray T, Lin C, Sanan DA. et al . Chronic overproduction of transforming growth factor-beta1 by astrocytes promotes Alzheimer's disease-like microvascular degeneration in transgenic mice. Am J Pathol. 2000; 156 139-150
21 Xu L, Li B, Cheng M. et al . Oral administration of grape seed proanthocyanidin extracts downregulate RAGE dependant nuclear factor- kappa BP65 expression in the hippocampus of streptozotocin induced diabetic rats. Exp Clin Endocrinol Diabetes. 2008; 116 215-224
22 Zhang XG, Yan H, Shen YL. et al . Decreased thrombospondin-I (TSP-I) expression in the hippocampus of streptozotocin-induced diabetic rats. Exp Clin Endocrinol Diabetes. 2008; 116 309-314

1 Yi Bao and Lei Jiang contributed equally to this work.

Correspondence

Prof. Z.-M. Liu

Department of Endocrinology

Changzheng Hospital

No. 415 FengYang Road

200003 Shanghai

China

Phone: +86/21/632 712 14

Fax: +86/21/632 712 14

Email: liu_zhimin2008@hotmail.com