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The effect of a single administration of streptozotocin on hippocampus metabolites in NODSCID mice

https://doi.org/10.18699/VJ18.400

Abstract

The significant increase in the number of people diagnosed with diabetes mellitus in recent years makes studies of this problem topical. The persistent hyperglycemia accompanying the development and course of type 1 diabetes mellitus (T1DM) can affect the func-tional and structural levels of the organization of the central nervous system. These changes may be medi­ated by metabolic aberrations. Magnetic resonance spectroscopy (MRS) is a common method of intravital detection of metabolic reactions. In this study, MRS of the hippocampus of NOD.CB17-Prkdcscid/NcrCrl mice (NODSCID) was performed 4 days after the administration of streptozotocin (STZ) to assess the effect of STZ itself, and 60 days after the administration of STZ to another group of animals to assess the effect of chronic hyperglycemia caused by the delayed ef­fect of STZ, involving the death of pancreatic β-cells. The simulation of T1DM by STZ administration is used worldwide. Nevertheless, the question remains whether there is a short-term effect of the introduc­tion of STZ at the level of hippocampal metabolites recorded by MRS. The comparison of experimental and control animal groups revealed no effect of STZ on metabolites in the hippocampus of NODSCID mice on day 4 after its administration. In contrast, another comparison of the experimental and control animals on day 60 after STZ administration showed elevated contents of alanine and taurine, and a reduced lactate content. Thus, the introduction of STZ itself does not affect the metabolism of the hippocampus, and MRS is a promising method for assessing the effect of T1DM on brain metabolism in animals.

About the Authors

D. A. Tur
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


O. B. Shevelev
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


M. В. Sharapova
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


M. A. Zolotykh
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


A. E. Akulov
Institute of Cytology and Genetics, SB RAS
Russian Federation
Novosibirsk


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51. Revsin Y., Rekers N.V., Louwe M.C., Saravia F.E., De Nicola A.F., de Kloet E.R., Oitzl M.S. Glucocorticoid receptor blockade normalizes hippocampal alterations and cognitive impairment in strepto¬zotocin-induced type 1 diabetes mice. Neuropsychopharmacology. 2009;34(3):747-758. DOI 10.1038/npp.2008.136.

52. Rose S.J., Bushi M., Nagra I., Davies W.E. Taurine fluxes in insulin de¬pendent diabetes mellitus and rehydration in streptozotocin treated rats. Adv. Exp. Med. Biol. 2000;483:497-501. DOI 10.1007/0-30646838-755.

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54. Sandler S., Swenne I. Streptozotocin, but not alloxan, induces DNA repair synthesis in mouse pancreatic islets in vitro. Diabetologia. 1983; 25(5):444-447.

55. Sarac K., Akinci A., Alkan A., Aslan M., Baysal T., Ozcan C. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus. Neuroradiology. 2005;47:562-565. DOI 10.1007/s00234-005-1387-3.

56. Schmidt R.E., Dorsey D.A., Beaudet L.N., Frederick K.E., Parvin C.A., Plurad S.B., Levisetti M.G. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy a new experimental model of diabetic autonomic neuropathy. Am. J. Pathol. 2003;163(5):20772091. DOI 10.1016/S0002-9440(10)63565-1.

57. Schnedl W.J., Ferber S., Johnson J.H., Newgard C.B. STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells. Diabetes. 1994;43(11):1326-1333. DOI 10.2337/diab.43.11.1326.

58. Sheshala R., Peh K.K., Darwis Y. Preparation, characterization, and in vivo evaluation of insulin-loaded PLA-PEG microspheres for controlled parenteral drug delivery. Drug Dev. Ind. Pharm. 2009;35(11): 1364-1374. DOI 10.3109/03639040902939213.

59. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res. 2001;50(6):537-546. DOI 10.1097/01.tp.0000189712.74495.82.

60. Tanabe M., Nitta A., Ono H. Neuroprotection via strychnine-sensitive glycine receptors during post-ischemic recovery of excitatory synaptic transmission in the hippocampus. J. Pharmacol. Sci. 2010; 113(4):378-386. DOI 10.1254/jphs.10150FP.

61. Terada T., Hara K., Haranishi Y., Sata T. Antinociceptive effect of in¬trathecal administration of taurine in rat models of neuropathic pain. Can. J. Anaesth. 2011;58(7):630-637. DOI 10.1007/s12630-0119504-8.

62. Timbrell J.A., Seabra V., Waterfield C.J. The in vivo and in vitro pro¬tective properties of taurine. Gen. Pharmacol. 1995;26(3):453-462. DOI 10.1016/0306-3623(94)00203-Y.

63. van Harten B., de Leeuw F.E., Weinstein H.C., Scheltens P., Biessels G.J. Brain imaging in patients with diabetes: a systematic review. Diabetes Care. 2006;29:2539-2548. DOI 10.2337/dc061637.

64. Wang W.T., Lee P., Yeh H.W., Smirnova I.V., Choi I.Y. Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo 1H MR spectroscopy at 9.4T. J. Neurochem. 2012;121:407-417. DOI 10.1111/j.1471-4159.2012.07698.x.

65. Weiss R.B. Streptozocin: a review of its pharmacology, efficacy, and toxicity. Cancer Treat. Rep. 1982;66:427-438.


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