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Stereological study of the effects of maternal diabetes on cerebellar cortex development in rat

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Abstract

Diabetes during pregnancy is associated with the deficits in balance and motor coordination and altered social behaviors in offspring. In the present study, we have investigated the effect of maternal diabetes and insulin treatment on the cerebellar volume and morphogenesis of the cerebellar cortex of rat neonates during the first two postnatal weeks. Sprague Dawley female rats were maintained diabetic from a week before pregnancy through parturition. At the end of pregnancy, the male offspring euthanized on postnatal days (P) 0, 7, and 14. Cavalieri’s principle and fractionator methods were used to estimate the cerebellar volume, the thickness and the number of cells in the different layers of the cerebellar cortex. In spite of P0, there was a significant reduction in the cerebellar volume and the thickness of the external granule, molecular, and internal granule layers between the diabetic and the control animals. In diabetic group, the granular and purkinje cell densities were increased at P0. Moreover, the number of granular and purkinje cells in the cerebellum of diabetic neonates was reduced in comparison with the control group at P7 and P14. There were no significant differences in either the volume and thickness or the number of cells in the different layers of the cerebellar cortex between the insulin-treated diabetic group and controls. Our data indicate that diabetes in pregnancy disrupts the morphogenesis of cerebellar cortex. This dysmorphogenesis may be part of the cascade of events through which diabetes during pregnancy affects motor coordination and social behaviors in offspring.

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References

  • Abusaad I, MacKay D, Zhao J, Stanford P, Collier DA, Everall IP (1999) Stereological estimation of the total number of neurons in the murine hippocampus using the optical disector. J Comp Neurol 408:560–566

    Article  CAS  PubMed  Google Scholar 

  • Altman J, Bayer SA (1996) Development of the cerebellar system: In relation to its evolution, structure, and functions. CRC Press, Boca Raton

    Google Scholar 

  • Alves-Wagner AB et al. (2015) Beta-adrenergic blockade increases GLUT4 and improves glycemic control in insulin-treated diabetic wistar rats. Auton neurosci: basic clin 193:108–116. doi:10.1016/j.autneu.2015.10.003

    Article  CAS  Google Scholar 

  • Anderson KM, Seed T, Ou D, Harris JE (1999) Free radicals and reactive oxygen species in programmed cell death. Med Hypotheses 52:451–463. doi:10.1054/mehy.1997.0521

    Article  CAS  PubMed  Google Scholar 

  • Anlar B, Sullivan KA, Feldman EL (1999) Insulin-like growth factor-I and central nervous system development. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 31:120–125. doi:10.1055/s-2007-978708

  • Babiker OO (2007) Long-term effects of maternal diabetes on their offspring development and behaviours. Sudanese J Ped 8:133–146

    Google Scholar 

  • Bahey NG, Soliman GM, El-Deeb TA, El-Drieny EA (2014) Influence of insulin and testosterone on diabetic rat ventral prostate: histological, morphometric and immunohistochemical study. J Microsc Ultrastruct 2:151

    Article  Google Scholar 

  • Baron-Van Evercooren A, Olichon-Berthe C, Kowalski A, Visciano G, Van Obberghen E (1991) Expression of IGF-I and insulin receptor genes in the rat central nervous system: a developmental, regional, and cellular analysis. J Neurosci Res 28:244–253

    Article  CAS  PubMed  Google Scholar 

  • Bartlett WP, Li XS, Williams M, Benkovic S (1991) Localization of insulin-like growth factor-1 mRNA in murine central nervous system during postnatal development. Dev Biol 147:239–250

    Article  CAS  PubMed  Google Scholar 

  • Beaton A, Marien P (2010) Language, cognition and the cerebellum: grappling with an enigma. Cortex; a J Devoted Study Nerv Syst Behav 46:811–820. doi:10.1016/j.cortex.2010.02.005

    Article  Google Scholar 

  • Benagiano V et al. (2007) Effects of prenatal exposure to the CB-1 receptor agonist WIN 55212-2 or CO on the GABAergic neuronal systems of rat cerebellar cortex. Neuroscience 149:592–601. doi:10.1016/j.neuroscience.2007.07.050

    Article  CAS  PubMed  Google Scholar 

  • Biran V, Verney C, Ferriero DM (2012) Perinatal cerebellar injury in human and animal models. Neurol Res Int 2012:858929. doi:10.1155/2012/858929

    Article  PubMed  PubMed Central  Google Scholar 

  • Bugalho P, Correa B, Viana-Baptista M (2006) [Role of the cerebellum in cognitive and behavioural control: scientific basis and investigation models] Acta medica portuguesa 19:257–267

  • Camprubi Robles M, Campoy C, Garcia Fernandez L, Lopez-Pedrosa JM, Rueda R, Martin MJ (2015) Maternal diabetes and cognitive performance in the offspring: A systematic review and Meta-Analysis. PLoS One 10:e0142583. doi:10.1371/journal.pone.0142583

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cardell BS (1953) Hypertrophy and hyperplasia of the pancreatic islets in new-born infants. J Pathol Bacteriol 66:335–346

    Article  CAS  PubMed  Google Scholar 

  • Castellucci M, Kaufmann P (1995) Basic structure of the villous trees. In: Benirschke K, Kaufmann P (eds) Pathology of the human placenta, 3 edn. Springer, New York, pp. 57–115

    Chapter  Google Scholar 

  • Cederberg J, Picard JJ, Eriksson UJ (2003) Maternal diabetes in the rat impairs the formation of neural-crest derived cranial nerve ganglia in the offspring. Diabetologia 46:1245–1251. doi:10.1007/s00125-003-1100-1

    Article  CAS  PubMed  Google Scholar 

  • Chandna AR, Kuhlmann N, Bryce CA, Greba Q, Campanucci VA, Howland JG (2015) Chronic maternal hyperglycemia induced during mid-pregnancy in rats increases RAGE expression, augments hippocampal excitability, and alters behavior of the offspring. Neuroscience 303:241–260. doi:10.1016/j.neuroscience.2015.06.063

    Article  CAS  PubMed  Google Scholar 

  • Chang TI, Horal M, Jain SK, Wang F, Patel R, Loeken MR (2003) Oxidant regulation of gene expression and neural tube development: insights gained from diabetic pregnancy on molecular causes of neural tube defects. Diabetologia 46:538–545. doi:10.1007/s00125-003-1063-2

    Article  CAS  PubMed  Google Scholar 

  • Clancy B, Finlay BL, Darlington RB, Anand KJ (2007) Extrapolating brain development from experimental species to humans. Neurotoxicology 28:931–937. doi:10.1016/j.neuro.2007.01.014

    Article  PubMed  Google Scholar 

  • Clutton S (1997) The importance of oxidative stress in apoptosis. Br Med Bull 53:662–668

    Article  CAS  PubMed  Google Scholar 

  • Comblath M, Schwartz R (1976) Disorders of carbohydrates metabolism in infancy, 2nd edn. WB Saunders, Philadelphia

    Google Scholar 

  • D’Angelo E, Casali S (2012) Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition. Front neural circ 6:116. doi:10.3389/fncir.2012.00116

    Google Scholar 

  • D Agostino AN, Bahn RC (1963) A histopathologic study of the pancreas of infants of diabetic mothers. Diabetes 12:327–331

  • de Pablo F, de la Rosa EJ (1995) The developing CNS: a scenario for the action of proinsulin, insulin and insulin-like growth factors. Trends Neurosci 18:143–150

    Article  PubMed  Google Scholar 

  • Dobbing J, Sands J (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 3:79–83

    Article  CAS  PubMed  Google Scholar 

  • Dowling D, Corrigan N, Horgan S, Watson CJ, Baugh J, Downey P, McAuliffe FM (2014) Cardiomyopathy in offspring of pregestational diabetic mouse pregnancy. J Diabetes Res 2014:624939. doi:10.1155/2014/624939

    Article  PubMed  PubMed Central  Google Scholar 

  • Eidelman AI, Samueloff A (2002) The pathophysiology of the fetus of the diabetic mother. Semin Perinatol 26:232–236

    Article  PubMed  Google Scholar 

  • Engelkamp D, Rashbass P, Seawright A, van Heyningen V (1999) Role of Pax6 in development of the cerebellar system. Development 126:3585–3596

    CAS  PubMed  Google Scholar 

  • Eriksson RS, Thunberg L, Eriksson UJ (1989a) Effects of interrupted insulin treatment on fetal outcome of pregnant diabetic rats. Diabetes 38:764–772

    Article  CAS  PubMed  Google Scholar 

  • Eriksson U, Dahlstrom E, Larsson KS, Hellerstrom C (1982) Increased incidence of congenital malformations in the offspring of diabetic rats and their prevention by maternal insulin therapy. Diabetes 31:1–6

    Article  CAS  PubMed  Google Scholar 

  • Eriksson UJ, Bone AJ, Turnbull DM, Baird JD (1989b) Timed interruption of insulin therapy in diabetic BB/E rat pregnancy: effect on maternal metabolism and fetal outcome. Acta Endocrinol (Copenh) 120:800–810

    CAS  Google Scholar 

  • Eriksson UJ, Borg LA (1991) Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia 34:325–331

    Article  CAS  PubMed  Google Scholar 

  • Eriksson UJ, Borg LA (1993) Diabetes and embryonic malformations. Role of substrate-induced free-oxygen radical production for dysmorphogenesis in cultured rat embryos Diabetes 42:411–419

    CAS  PubMed  Google Scholar 

  • Eriksson UJ, Siman CM (1996) Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring. Diabetes 45:1497–1502

    Article  CAS  PubMed  Google Scholar 

  • Fonnum F, Lock EA (2000) Cerebellum as a target for toxic substances. Toxicol Lett 112-113:9–16

    Article  CAS  PubMed  Google Scholar 

  • Freitas HS, Schaan BD, Seraphim PM, Nunes MT, Machado UF (2005) Acute and short-term insulin-induced molecular adaptations of GLUT2 gene expression in the renal cortex of diabetic rats. Mol Cell Endocrinol 237:49–57. doi:10.1016/j.mce.2005.03.005

    Article  CAS  PubMed  Google Scholar 

  • Gardella D, Hatton WJ, Rind HB, Rosen GD, von Bartheld CS (2003) Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections. J Neurosci Methods 124:45–59

    Article  PubMed  Google Scholar 

  • Geuna S, Herrera-Rincon C (2015) Update on stereology for light microscopy. Cell Tissue Res 360:5–12. doi:10.1007/s00441-015-2143-6

    Article  PubMed  Google Scholar 

  • Golalipour MJ, Kafshgiri SK, Ghafari S (2012) Gestational diabetes induced neuronal loss in CA1 and CA3 subfields of rat hippocampus in early postnatal life. Folia Morphol (Warsz) 71:71–77

    CAS  Google Scholar 

  • Gonzalez-Burgos I, Alejandre-Gomez M (2005) Cerebellar granule cell and Bergmann glial cell maturation in the rat is disrupted by pre- and post-natal exposure to moderate levels of ethanol. International Journal of Developmental Neuroscience: the Official Journal of the International Society For Developmental Neuroscience 23:383–388. doi:10.1016/j.ijdevneu.2004.11.002

    Article  CAS  Google Scholar 

  • Gressens P (2006) Pathogenesis of migration disorders. Curr Opin Neurol 19:135–140. doi:10.1097/01.wco.0000218228.73678.e1

    Article  CAS  PubMed  Google Scholar 

  • Guillery RW (2002) On counting and counting errors. J Comp Neurol 447:1–7. doi:10.1002/cne.10221

    Article  CAS  PubMed  Google Scholar 

  • Gundersen HJ (1986) Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson. J Microsc 143:3–45

    Article  CAS  PubMed  Google Scholar 

  • Gundersen HJ et al. (1988a) The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96:857–881

    Article  CAS  PubMed  Google Scholar 

  • Gundersen HJ et al. (1988b) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96:379–394

    Article  CAS  PubMed  Google Scholar 

  • Hagay ZJ, Weiss Y, Zusman I, Peled-Kamar M, Reece EA, Eriksson UJ, Groner Y (1995) Prevention of diabetes-associated embryopathy by overexpression of the free radical scavenger copper zinc superoxide dismutase in transgenic mouse embryos. Am J Obstet Gynecol 173:1036–1041

    Article  CAS  PubMed  Google Scholar 

  • Haghir H, Rezaee AA, Sankian M, Kheradmand H, Hami J (2013) 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 28:397–410. doi:10.1007/s11011-013-9386-2

    Article  CAS  PubMed  Google Scholar 

  • Hami J, Karimi R, Haghir H, Gholamin M, Sadr-Nabavi A (2015a) Diabetes in pregnancy adversely affects the expression of glycogen synthase kinase-3beta in the hippocampus of rat neonates. J Mol Neurosci 57:273–281. doi:10.1007/s12031-015-0617-3

    Article  CAS  PubMed  Google Scholar 

  • Hami J, Kerachian MA, Karimi R, Haghir H, Sadr-Nabavi A (2015b) Effects of streptozotocin-induced type 1 maternal diabetes on PI3K/AKT signaling pathway in the hippocampus of rat neonates. J Recept Signal Transduct Res: 1–7. doi:10.3109/10799893.2015.1086884

  • Hami J, Sadr-Nabavi A, Sankian M, Balali-Mood M, Haghir H (2013) The effects of maternal diabetes on expression of insulin-like growth factor-1 and insulin receptors in male developing rat hippocampus. Brain Struct Funct 218:73–84. doi:10.1007/s00429-011-0377-y

    Article  CAS  PubMed  Google Scholar 

  • Hami J, Shojae F, Vafaee-Nezhad S, Lotfi N, Kheradmand H, Haghir H (2015c) Some of the experimental and clinical aspects of the effects of the maternal diabetes on developing hippocampus. World journal of diabetes 6:412–422. doi:10.4239/wjd.v6.i3.412

    Article  PubMed  PubMed Central  Google Scholar 

  • Hami J, Vafaei-Nezhad S, Haghir D, Haghir H (2015d) Insulin-like growth factor-1 receptor Is differentially distributed in developing cerebellar cortex of rats born to diabetic mothers. J Mol Neurosci. doi:10.1007/s12031-015-0661-z

    Google Scholar 

  • Hawkins CL, Davies MJ (2001) Generation and propagation of radical reactions on proteins. Biochim Biophys Acta 1504:196–219

    Article  CAS  PubMed  Google Scholar 

  • Hernandez-Fonseca JP, Rincon J, Pedreanez A, Viera N, Arcaya JL, Carrizo E, Mosquera J (2009) Structural and ultrastructural analysis of cerebral cortex, cerebellum, and hypothalamus from diabetic rats. Exp Diabetes Res 2009:329632. doi:10.1155/2009/329632

    Article  PubMed  PubMed Central  Google Scholar 

  • Howard CV, Reed MG (1998) Unbiased stereology: three-dimensional measurement in microscopy. Bios Scientific Publisher, Oxford

    Google Scholar 

  • Jackson-Guilford J, Leander JD, Nisenbaum LK (2000) The effect of streptozotocin-induced diabetes on cell proliferation in the rat dentate gyrus. Neurosci Lett 293:91–94

    Article  CAS  PubMed  Google Scholar 

  • Jawerbaum A, White V (2010) Animal models in diabetes and pregnancy. Endocr Rev 31:680–701. doi:10.1210/er.2009-0038

    Article  PubMed  Google Scholar 

  • Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 48:2129–2139. doi:10.1172/JCI106180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kafshgiri SK, Ghafari S, Golalipour MJ (2014) Gestational diabetes induces neuronal loss in dentate gyrus in rat offspring. J Neurol Sci [Turkish] 31:316–324

    Google Scholar 

  • Kamal A, Biessels GJ, Urban IJ, Gispen WH (1999) Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression. Neuroscience 90:737–745

    Article  CAS  PubMed  Google Scholar 

  • Khaksar Z, Jelodar GA, Hematian H (2011) Morphometric study of cerebrum in fetuses of diabetic mothers. Iranian Journal of Veterinary Research 12:199–204

    Google Scholar 

  • Lapolla A, Dalfra MG, Fedele D (2005) Insulin therapy in pregnancy complicated by diabetes: are insulin analogs a new tool? Diabetes Metab Res Rev 21:241–252. doi:10.1002/dmrr.551

    Article  CAS  PubMed  Google Scholar 

  • Lin X, Bulleit RF (1997) Insulin-like growth factor I (IGF-I) is a critical trophic factor for developing cerebellar granule cells. Brain Res Dev Brain Res 99:234–242

    Article  CAS  PubMed  Google Scholar 

  • Lopes CD, Sinigaglia-Coimbra R, Mazzola J, Camano L, Mattar R (2011) Neurofunctional evaluation of young Male offspring of rat dams with diabetes induced by streptozotocin. ISRN Endocrinology. doi:10.5402/2011/480656

    Google Scholar 

  • Malomo AO, Imosemi IO, Osuagwu FC, Oladejo OW, Akang EE, Shokunbi MT (2004) Histomorphometric studies on the effect of cyanide consumption of the developing cerebellum of wistar rat (rattus novergicus). West Afr J Med 23:323–328

    CAS  PubMed  Google Scholar 

  • Manto M et al. (2012) Consensus paper: roles of the cerebellum in motor control–the diversity of ideas on cerebellar involvement in movement. Cerebellum 11:457–487. doi:10.1007/s12311-011-0331-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Moazzen H, Lu X, Liu M, Feng Q (2015) Pregestational diabetes induces fetal coronary artery malformation via reactive oxygen species signaling. Diabetes 64:1431–1443. doi:10.2337/db14-0190

    Article  CAS  PubMed  Google Scholar 

  • Mouton PR (2002) Principles and practices of unbiased stereology: an introduction for bioscientists. Johns Hopkins University Press, Baltimore

    Google Scholar 

  • Mwangi DK (2001) Cerebellar parameters in developing 15 day old rat pups treated with propylthiouracil in comparison with 5 and 24 day old. East Afr Med J 78:322–326

    Article  CAS  PubMed  Google Scholar 

  • Nelson CA, Wewerka S, Thomas KM, Tribby-Walbridge S, deRegnier R, Georgieff M (2000) Neurocognitive sequelae of infants of diabetic mothers. Behav Neurosci 114:950–956

    Article  CAS  PubMed  Google Scholar 

  • Odaci E et al. (2004) Effects of low-dose oxcarbazepine administration on developing cerebellum in newborn rat: A stereological study. Neurosci Res Commun 34:28–36

    Article  CAS  Google Scholar 

  • Ornoy A (2005) Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes. Pediatr Endocrinol Rev 3:104–113

    PubMed  Google Scholar 

  • Ornoy A, Ratzon N, Greenbaum C, Peretz E, Soriano D, Dulitzky M (1998) Neurobehaviour of school age children born to diabetic mothers. Arch Dis Child Fetal Neonatal Ed 79:F94–F99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ornoy A, Ratzon N, Greenbaum C, Wolf A, Dulitzky M (2001) School-age children born to diabetic mothers and to mothers with gestational diabetes exhibit a high rate of inattention and fine and gross motor impairment. J Pediatr Endocrinol Metab 14(Suppl 1):681–689

    PubMed  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  • Persaud OD (2007) Maternal diabetes and the consequences for her offspring. J Develop Disab 1:101–134

    Google Scholar 

  • Petersen MB, Pedersen SA, Greisen G, Pedersen JF, Mølsted-Pedersen L (1988) Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4. Br Med J (Clin Res Ed) 296:598–600

    Article  CAS  Google Scholar 

  • Pettitt DJ, Bennett PH (1995) Long-term outcome of infant of diabetic mothers. In: Reece AE, Coustan DR (eds) Diabetes mellitus in pregnancy, 2 edn. Churchill Livingstone, New York, pp. 379–388

    Google Scholar 

  • Popken GJ, Hodge RD, Ye P, Zhang J, Ng W, O’Kusky JR, D’Ercole AJ (2004) In vivo effects of insulin-like growth factor-I (IGF-I) on prenatal and early postnatal development of the central nervous system. The European J Neuroscience 19:2056–2068. doi:10.1111/j.0953-816X.2004.03320.x

    Article  Google Scholar 

  • Ratzon N, Greenbaum C, Dulitzky M, Ornoy A (2000) Comparison of the motor development of school-age children born to mothers with and without diabetes mellitus. Phys Occup Ther Pediatr 20:43–57

    Article  CAS  PubMed  Google Scholar 

  • Rizzo T, Metzger BE, Burns WJ (1991) Burns K. Correlations between antepartum maternal metabolism and child intelligence N Engl J Med 325:911–916. doi:10.1056/NEJM199109263251303

    CAS  PubMed  Google Scholar 

  • Rizzo TA, Dooley SL, Metzger BE, Cho NH, Ogata ES, Silverman BL (1995) Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol 173:1753–1758

    Article  CAS  PubMed  Google Scholar 

  • Rudow G et al. (2008) Morphometry of the human substantia nigra in ageing and Parkinson’s disease. Acta Neuropathol 115:461–470. doi:10.1007/s00401-008-0352-8

    Article  PubMed  PubMed Central  Google Scholar 

  • Ryder EF, Cepko CL (1994) Migration patterns of clonally related granule cells and their progenitors in the developing chick cerebellum. Neuron 12:1011–1028

    Article  CAS  PubMed  Google Scholar 

  • Schwartz R, Teramo KA (2000) Effects of diabetic pregnancy on the fetus and newborn. Semin Perinatol 24:120–135

    Article  CAS  PubMed  Google Scholar 

  • Shin BC, Fujikura K, Suzuki T, Tanaka S, Takata K (1997) Glucose transporter GLUT3 in the rat placental barrier: a possible machinery for the transplacental transfer of glucose. Endocrinology 138:3997–4004

    Article  CAS  PubMed  Google Scholar 

  • Siman CM, Eriksson UJ (1997a) Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic rats. Diabetologia 40:1416–1424. doi:10.1007/s001250050844

    Article  CAS  PubMed  Google Scholar 

  • Siman CM, Eriksson UJ (1997b) Vitamin E decreases the occurrence of malformations in the offspring of diabetic rats. Diabetes 46:1054–1061

    Article  CAS  PubMed  Google Scholar 

  • Singh BS, Westfall TC, Devaskar SU (1997) Maternal diabetes-induced hyperglycemia and acute intracerebral hyperinsulinism suppress fetal brain neuropeptide Y concentrations. Endocrinology 138:963–969

    CAS  PubMed  Google Scholar 

  • Sivan E, Reece EA, Wu YK, Homko CJ, Polansky M, Borenstein M (1996) Dietary vitamin E prophylaxis and diabetic embryopathy: morphologic and biochemical analysis. Am J Obstet Gynecol 175:793–799

    Article  CAS  PubMed  Google Scholar 

  • Som S et al. (1981) Ascorbic acid metabolism in diabetes mellitus. Metabolism 30:572–577

    Article  CAS  PubMed  Google Scholar 

  • Sterio DC (1984) The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134:127–136

    Article  CAS  PubMed  Google Scholar 

  • Styrud J, Thunberg L, Nybacka O, Eriksson UJ (1995) Correlations between maternal metabolism and deranged development in the offspring of normal and diabetic rats. Pediatr Res 37:343–353

    Article  CAS  PubMed  Google Scholar 

  • Takata K, Fujikura K, Shin BC (1997) Ultrastructure of the rodent placental labyrinth: a site of barrier and transport. J Reprod Develop 43:13–24

    Article  Google Scholar 

  • Tapias V, Greenamyre JT, Watkins SC (2013) Automated imaging system for fast quantitation of neurons, cell morphology and neurite morphometry in vivo and in vitro. Neurobiol Dis 54:158–168. doi:10.1016/j.nbd.2012.11.018

    Article  PubMed  PubMed Central  Google Scholar 

  • Tehranipour M, Khakzad MR (2008) Effect of maternal diabetes on hippocampus neuronal density in neonatal rats. J Biol Sci 8:1027–1032

    Article  Google Scholar 

  • Torres-Aleman I, Pons S, Arevalo MA (1994) The insulin-like growth factor I system in the rat cerebellum: developmental regulation and role in neuronal survival and differentiation. J Neurosci Res 39:117–126. doi:10.1002/jnr.490390202

    Article  CAS  PubMed  Google Scholar 

  • Van Lieshout RJ, Voruganti LP (2008) Diabetes mellitus during pregnancy and increased risk of schizophrenia in offspring: a review of the evidence and putative mechanisms. J psychiatry neuroscience: JPN 33:395–404

    Google Scholar 

  • Viana M, Herrera E, Bonet B (1996) Teratogenic effects of diabetes mellitus in the rat. Prevention with Vitamin E Diabetologia 39:1041–1046

    CAS  PubMed  Google Scholar 

  • von Bartheld C (2002) Counting particles in tissue sections: choices of methods and importance of calibration to minimize biases. Histol Histopathol 17:639–648

    Google Scholar 

  • von Bartheld CS (2012) Distribution of particles in the Z-axis of tissue sections: relevance for counting methods. NeuroQuantology: An Interdisciplinary J Neurosci Quantum Physics 10:66–75

    Google Scholar 

  • Wentzel P, Thunberg L, Eriksson UJ (1997) Teratogenic effect of diabetic serum is prevented by supplementation of superoxide dismutase and N-acetylcysteine in rat embryo culture. Diabetologia 40:7–14. doi:10.1007/s001250050636

    Article  CAS  PubMed  Google Scholar 

  • Xiang AH et al. (2015) Association of maternal diabetes with autism in offspring. JAMA 313:1425–1434. doi:10.1001/jama.2015.2707

    Article  CAS  PubMed  Google Scholar 

  • Yamano T, Shimada M, Yoshiki F, Kawasaki H, Onaga A (1986) Quantitative synaptic changes on purkinjie cell dendritic spines of rats born from streptozotocin-induced diabetic mothers. Brain Dev 8:269–273

    Article  CAS  PubMed  Google Scholar 

  • Yong Y et al. (2015) PACT/RAX regulates the migration of cerebellar granule neurons in the developing cerebellum. Sci Report 5:7961. doi:10.1038/srep07961

    Article  CAS  Google Scholar 

  • Zhou J, Wang L, Ling S, Zhang X (2007) Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats. Exp Neurol 206:201–208. doi:10.1016/j.expneurol.2007.04.013

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Yu T, Rao Y (2004) Temporal regulation of cerebellar EGL migration through a switch in cellular responsiveness to the meninges. Dev Biol 267:153–164. doi:10.1016/j.ydbio.2003.10.037

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the vice chancellor of Research of Birjand University of Medical Sciences for financial support of this research (Grant number:1288).

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Javad Hami, Saeed Vafaei-nezhad, Ghasem Ivar & Fatemeh Shojae

  2. Department of Neurosurgery, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Kazem Ghaemi

  3. Department of Anatomy and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Akram Sadeghi

  4. Department of Public Health, Research Centre of Experimental Medicine, Deputy of Research and Technology, Birjand University of Medical Sciences, Birjand, Iran

    Mehran Hosseini

  5. Cellular & Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran

    Javad Hami

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Hami, J., Vafaei-nezhad, S., Ghaemi, K. et al. Stereological study of the effects of maternal diabetes on cerebellar cortex development in rat. Metab Brain Dis 31, 643–652 (2016). https://doi.org/10.1007/s11011-016-9802-5

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  • DOI: https://doi.org/10.1007/s11011-016-9802-5

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