Tuğba KOTİL, Adem YILMAZ, Feray AKBAŞ, Nuriye Güzin ÖZDEMİR

Analysis of diabetes-related cerebellar changes in streptozotocin-induced diabetic rats

Background/aim: Diabetic peripheral neuropathy has been extensively studied and reported, but the number of studies that have investigated diabetes-related changes in the central nervous system are limited, with even fewer studies on the cerebellum. The aim of this experimental study was to perform a histologic analysis of the diabetes-related changes in the cerebellums of diabetic rats. Materials and methods: Twenty Sprague Dawley rats weighing between 200 and 220 g were included in the study. Diabetes was induced in 14 of these rats by a single intraperitoneal injection of 65 mg/kg streptozotocin dissolved in saline, while 6 animals constituted the control group. The induction of diabetes was confirmed by measuring the blood glucose levels in the tail blood with a glucometer. Levels equal to or above 200 mg/dL were considered diabetic. Induction of diabetes failed in 3 animals, who were then excluded from the study. Results: Light and electron microscopic studies revealed that the neurons and glial cells in the diabetic group had degenerative changes, irregularities and disruption in the myelin sheath, disintegration in the presynaptic vesicles, engorged axon terminals, perivascular and mitochondrial swelling, mitochondrial structural changes, and fragmentation of the neurofilaments. Conclusion: Ultrastructural alterations are observed in the diabetic rat cerebellum.

PDF

___

1. Guven A, Yavuz O, Cam M, Comunoglu C, Sevinc O. Central nervous system complications of diabetes in streptozotocin-induced diabetic rats: a histopathological and immunohistochemical examination. Int J Neurosci 2009; 119: 1155-1169.
2. Antony S, Peeyush Kumar T, Mathew J, Anju TR, Paulose CS. Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats. J Biomed Sci 2010; 17: 7.
3. Derakhshan F, Toth C. Insulin and the brain. Curr Diabetes Rev 2013; 9: 102-116.
4. Aydın S, Kuloglu T, Aydın S, Eren MN, Yılmaz M, Kalaycı M, Sahin I, Kocaman N, Citil C, Kendir Y. Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem 2013; 380: 73-81.
5. Kara A, Unal D, Simsek N, Yucel A, Yucel N, Selli J. Ultrastructural changes and apoptotic activity in cerebellum of postmenopausal-diabetic rats: a histochemical and ultra-structural study. Gynecol Endocrinol 2014; 30: 226-231.
6. Lechuga-Sancho AM, Arroba AI, Frago LM, Pañeda C, GarcíaCáceres C, Delgado Rubín de Célix A, Argente J, Chowen JA. Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats. Neurobiol Dis 2006; 23: 290-299.
7. Hernández-Fonseca JP, Rincón J, Pedreañez A, Viera N, Arcaya JL, Carrizo E, Mosquera J. Structural and ultrastructural analysis of cerebral cortex, cerebellum, and hypothalamus from diabetic rats. Exp Diabetes Res 2009; 2009: 329632.
8. Selim SA, Selim AO. Effect of streptozotocin-induced diabetes mellitus on the cerebellar cortex of adult male albino rats: histological and immunohistochemical study. The Egyptian Journal of Histology 2013; 36: 103-113.
9. Kumar TP, Antony S, Gireesh G, George N, Paulose CS. Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats. J Biomed Sci 2010; 17: 43-51.
10. Shanmugam KR, Mallikarjuna K, Kesireddy N, Sathyavelu Reddy K. Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats. Food Chem Toxicol 2011; 49: 893-897.
11. Türeci E, İş M, Üzüm G, Akyüz F, Ulu MO, Döşoğlu M, Uzan M: Alterations in blood-brain barrier after traumatic brain injury in streptozotocin-induced diabetic rats. Sinir Sistemi Cerrahisi Dergisi 2009; 2: 79-86.
12. Yamano T, Shimada M, Fujizeki Y, Kawasaki H, Onaga A. Quantitative synaptic changes on Purkinje cell dendritic spines of rats born from streptozotocin-induced diabetic mothers. Brain Dev 1986; 8: 269-273.
13. Jeremy JY, Mikhailidis DP, Thompson CS, Dandona P. Changes in eicosanoid synthesis in the cerebrum, cerebellum and brainstem of the diabetic rat. Diabetes Res 1987; 6: 95-98.
14. Bruhlmann-Papazyan M, Garcia-Segura LM, Pizzolato GP, Norman AW, Orcı L. Immunohistochemically detectable vitamin D-dependent calcium-binding protein is reduced in cerebellum of diabetic subjects. Diabetes 1984; 33: 917-922.
15. Honnorat J, Saiz A, Giometto B, Vincent A, Brieva L, de Andres C, Maestre J, Fabien N, Vighetto A, Casamitjana R. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 2001; 58: 225-230.
16. Iwasaki H, Sato R, Shichiri M, Hirata Y. A patient with type 1 diabetes mellitus and cerebellar ataxia associated with high titer of circulating anti-glutamic acid decarboxylase antibodies. Endocr J 2001; 48: 261-268.
17. Pedroso JL, Braga-Neto P, Dutra LA, Barsottini OG. Cerebellar ataxia associated to anti-glutamic acid decarboxylase autoantibody (anti-GAD). Arq Neuropsiquiatr 2011; 69: 993.
18. Haghir H, Rezaee AA, Sankian M, Kheradmand H, Hami J. The effects of induced type-I diabetes on developmental regulation of insulin & insulin like growth factor-1 (IGF-1) receptors in the cerebellum of rat neonates. Metab Brain Dis 2013; 28: 397- 410.
19. Hoveyda N, Shield JP, Garrett C, Chong WK, Beardsall K, Bentsi-Enchill E, Mallya H, Thompson MH. Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome. J Med Genet 1999; 36: 700-704.
20. Biju MP, Paulose CS. Brain glutamate dehydrogenase changes in streptozotocin diabetic rats as a function of age. Biochem Mol Biol Int 1998; 44: 1-7.