Time course changes of amyloid-β peptide-binding alcohol dehydrogenase and choline acetyl transferase in hippocampus of diabetic mice

doi:10.3969/j.issn.1006-7795.2013.01.010

Abstract

Abstract:

Objective To observe the time course changes of expression of amyloid-β peptide-binding alcohol dehydrogenase (ABAD) and choline acetyl transferase (ChAT) in the hippocampal CA1 region of diabetic mice, in order to explore the mechanism of diabetic encephalopathy.Methods Forty-eight male mice were divided into a control (C) group (n=24) and a diabetes mellitus (DM) group (n=24) randomly. Streptozocin (STZ) was freshly prepared and injected at 200 mg/kg, i.p. into mice which had been fasted for 12 h. Three days later, blood glucose in a tail-vein sample was determined; a value ≥15 mmol/L was accepted as a successful induction of a diabetic model. The expression changes of ABAD and ChAT in the hippocampus of group C and DM group mice at 1 week, 4 weeks and 8 weeks after DM models establishment were studied by immunohistochemical staining. Results 1) The result of ABAD immunohistochemical staining showed that there were slightly stained ABAD-positive cells in hippocampal CA1 region of group C mice,while more darkly stained ABAD-positive cells in hippocampal CA1 region were found in DM group mice at 1 week, 4 weeks and 8 weeks. The numbers of ABAD-positive cells in the hippocampal CA1 region of DM group mice at 1 week, 4 weeks and 8 weeks (18.50±2.72,21.10±2.47,18.90±2.08) increased significantly (P<0.01) compared with those of group C mice (14.30±2.63, 15.30±3.13, 14.10±3.07). 2) The ChAT immunohistochemical staining showed that there were some darkly stained ChAT-positive cells in hippocampal CA1 region of group C mice,while DM group mice at 1 week, 4 weeks and 8 weeks had less ChAT-positive cells in hippocampal CA1 region compared with those of group C, the staining was pale. The numbers of ChAT-positive cells in the hippocampal CA1 region of DM group mice at 1 week, 4 weeks and 8 weeks (21.20±2.15,19.60±3.50,21.30±3.20) decreased significantly (P<0.01) compared with those of group C mice(25.50±3.63, 26.40±3.37, 26.30±4.88).Conclusion The expression of ABAD in hippocampus of DM mice increased compared with that of normal control mice at early stage of DM (1 week) and sustained till the end of this study (DM 8 weeks). Meanwhile, the expression of ChAT cells in hippocampus of DM mice decreased significantly. ABAD might be involved in the degeneration of cholinergic neuron in DM mice and play important role in the pathogenesis of diabetic encephalopathy.

Key words: diabetes mellitus, hippocampus, amyloid-&beta, peptide-binding alcohol dehydrogenase, choline acetyl transferase

CLC Number:

R587.1

YAN Ying, LI Sen, ZHAO Zhiwei, ZHAO Yongmei. Time course changes of amyloid-β peptide-binding alcohol dehydrogenase and choline acetyl transferase in hippocampus of diabetic mice[J]. Journal of Capital Medical University, 2013, 34(1): 53-57.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2013.01.010

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2013/V34/I1/53

References

[1] Mijnhout G S, Scheltens P, Diamant M, et al. Diabetic encephalopathy: a concept in need of a definition [J]. Diabetologia, 2006, 49(6): 1447-1448.

[2] Kamboj S S, Chopra K, Sandhir R. Neuroprotective effect of N-acetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes [J]. Metab Brain Dis, 2008,23(4):427-443.

[3] Zhao Y M, Pei J J, Ji Z J, et al. Effect of amyloid precursor protein 17mer peptide on microtubule structure and tau protein hyperphosphorylation in hippocampal neurons of experimental diabetic mice [J]. Neuroreport, 2003, 14(1): 61-66.

[4] Shuli S, Yongmei Z, Zhiwei Z, et al. beta-Amyloid and its binding protein in the hippocampus of diabetic mice: effect of APP17 peptide [J]. Neuroreport, 2001, 12(15): 3317-3319.

[5] Yan S D, Fu J, Soto C, et al. An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease [J]. Nature, 1997, 389(6652):689-695.

[6] Marques A T, Fernandes P A, Ramos M J. ABAD: a potential therapeutic target for Abeta-induced mitochondrial dysfunction in Alzheimer's disease [J]. Mini Rev Med Chem, 2009, 9(8):1002-1008.

[7] Lim Y A, Grimm A, Giese M, et al. Inhibition of the mitochondrial enzyme ABAD restores the amyloid-β-mediated deregulation of estradiol [J]. PLoS One, 2011, 6(12):e28887.

[8] Yao J, Du H, Yan S, et al. Inhibition of amyloid-beta (Abeta) peptide-binding alcohol dehydrogenase-Abeta interaction reduces Abeta accumulation and improves mitochondrial function in a mouse model of Alzheimer's disease [J]. J Neurosci, 2011, 31(6):2313-2320.

[9] Sherin A, Anu J, Peeyush K T, et al. Cholinergic and GABAergic receptor functional deficit in the hippocampus of insulin-induced hypoglycemic and streptozotocin-induced diabetic rats [J]. Neuroscience, 2012, 202(1):69-76.

[10] 闫颖,赵咏梅,赵志炜,等. 内质网应激通路相关分子GRP78及CHOP在糖尿病脑病小鼠海马表达的变化 [J]. 首都医科大学学报, 2011,32(1):90-94.

[11] Lustbader J W, Cirilli M, Lin C, et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease [J]. Science, 2004, 304(5669):448-452.

[12] Yao J, Irwin R, Chen S, et al. Ovarian hormone loss induces bioenergetic deficits and mitochondrial β-amyloid [J]. Neurobiol Aging, 2012, 33(8):1507-1521.

[13] Muresan V, Muresan Z. A persistent stress response to impeded axonal transport leads to accumulation of amyloid-β in the endoplasmic reticulum, and is a probable cause of sporadic Alzheimer's disease [J]. Neurodegener Dis, 2012, 10(1-4):60-63.

[14] Kim H J, Cho H K, Kwon Y H. Synergistic induction of ER stress by homocysteine and beta-amyloid in SH-SY5Y cells [J]. J Nutr Biochem, 2008, 19(11):754-761.

[15] Stranahan A M, Arumugam T V, Cutler R G, et al. Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons [J]. Nat Neurosci, 2008, 11(3):309-317.