Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of hypothyroidism on cell proliferation and neuroblasts in the hippocampal dentate gyrus in a rat model of type 2 diabetes

  • Yi, Sun-Shin (Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University) ;
  • Hwang, In-Koo (Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University) ;
  • Choi, Ji-Won (Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University) ;
  • Won, Moo-Ho (Department of Neurobiology, School of Medicine, Kangwon National University) ;
  • Seong, Je-Kyung (Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University) ;
  • Yoon, Yeo-Sung (Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University)
  • Received : 2010.07.13
  • Accepted : 2010.09.02
  • Published : 2010.09.30
⟨ Previous Next ⟩

Abstract

We observed how the hypothyroid state affects diabetic states and modifies cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG). For this, 0.03% methimazole, an anti-thyroid drug, was administered to 7-week-old, pre-diabetic Zucker diabetic fatty (ZDF) rats by drinking water for 5 weeks, and the animals were sacrificed at 12 weeks of age. At this age, corticosterone levels were significantly increased in the ZDF rats compared to those in the control (Zucker lean control, ZLC) rats. Methimazole (methi) treatment in the ZDF rats (ZDF-methi rats) significantly decreased corticosterone levels and diabetes-induced hypertrophy of adrenal glands. In the DG, Ki67 (a marker for cell proliferation)- and doublecortin (DCX, a marker for neuronal progenitors)-immunoreactive cells were much lower in the ZDF rats than those in the ZLC rats. However, in ZDF-methi rats, numbers of Ki67- and DCX-immunoreactive cells were similar to those in the ZLC rats. These suggest that methi significantly reduces diabetes-induced hypertrophy of the adrenal gland and alleviates the diabetes-induced reduction of cell proliferation and neuronal progenitors in the DG.

Keywords

Acknowledgement

Grant : Regional Core Research Program

Supported by : Korea Ministry of Education, Science and Technology (Medical & Bio-material Research Center)

References

  1. Aizawa K, Ageyama N, Yokoyama C, Hisatsune T. (2009). Age-dependent alteration in hippocampal neurogenesis correlates with learning performance of macaque monkeys. Exp Anim 58: 403-407 https://doi.org/10.1538/expanim.58.403
  2. Ambrogini P, Cuppini R, Ferri P, et al. (2005). Thyroid hormones affect neurogenesis in the dentate gyrus of adult rat. Neuroendocrinology 81: 244-253. https://doi.org/10.1159/000087648
  3. Auso E, Lavado-Autric R, Cuevas E, Del Rey FE, Morreale De Escobar G, Berbel P. (2004). A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration. Endocrinology 145: 4037-4047 https://doi.org/10.1210/en.2004-0274
  4. Beauquis J, Roig P, Homo-Delarche F, De Nicola A, Saravia F. (2006). Reduced hippocampal neurogenesis and number of hilar neurones in streptozotocin-induced diabetic mice: reversion by antidepressant treatment. Eur J Neurosci 23: 1539-1546 https://doi.org/10.1111/j.1460-9568.2006.04691.x
  5. Bernal J, Guadano-Ferraz A, Morte B. (2003). Perspectives in the study of thyroid hormone action on brain development and function. Thyroid 13: 1005-1012 https://doi.org/10.1089/105072503770867174
  6. Carageorgiou H, Pantos C, Zarros A, et al. (2007). Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats. Metabolism 56: 1104-1110 https://doi.org/10.1016/j.metabol.2007.04.003
  7. Cooper DS. (2005). Antithyroid drugs. N Engl J Med 352: 905-917 https://doi.org/10.1056/NEJMra042972
  8. Cooper-Kuhn CM, Kuhn HG. (2002). Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain. Brain Res Dev Brain Res 134: 13-21 https://doi.org/10.1016/S0165-3806(01)00243-7
  9. Cuevas E, Auso E, Telefont M, Morreale de Escobar G, Sotelo C, Berbel P. (2005). Transient maternal hypothyroxinemia at onset of corticogenesis alters tangential migration of medial ganglionic eminence-derived neurons. Eur J Neurosci 22: 541-551 https://doi.org/10.1111/j.1460-9568.2005.04243.x
  10. Etgen GJ, Oldham BA. (2000). Profiling of Zucker diabetic fatty rats in their progression to the overt diabetic state. Metabolism 49: 684-688 https://doi.org/10.1016/S0026-0495(00)80049-9
  11. Gispen WH, Biessels GJ. (2000). Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 23: 542-549 https://doi.org/10.1016/S0166-2236(00)01656-8
  12. Hastings NB, Gould E. (1999). Rapid extension of axons into the CA3 region by adult-generated granule cells. J Comp Neurol 413: 146-154 https://doi.org/10.1002/(SICI)1096-9861(19991011)413:1<146::AID-CNE10>3.0.CO;2-B
  13. Hibbe T, Kiesel U, Kolb-Bachofen V, Kolb H. (1991). Methimazole treatment aggravates low-dose streptozotocin-induced diabetes. Diabetes Res Clin Pract 11: 53-58 https://doi.org/10.1016/0168-8227(91)90141-Y
  14. Hwang IK, Kim IY, Kim YN, et al. (2009). Effects of methimazole on the onset of type 2 diabetes in leptin receptor-deficient rats. J Vet Med Sci 71: 275-280 https://doi.org/10.1292/jvms.71.275
  15. Hwang IK, Yi SS, Kim YN, et al. (2008). Reduced hippocampal cell differentiation in the subgranular zone of the dentate gyrus in a rat model of type II diabetes. Neurochem Res 33: 394-400 https://doi.org/10.1007/s11064-007-9440-8
  16. 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 https://doi.org/10.1016/S0304-3940(00)01502-0
  17. Joels M. (2007). Role of corticosteroid hormones in the dentate gyrus. Prog Brain Res 163: 355-370 https://doi.org/10.1016/S0079-6123(07)63021-0
  18. Karl C, Couillard-Despres S, Prang P, et al. (2005). Neuronal precursor-specific activity of a human doublecortin regulatory sequence. J Neurochem 92: 264-282 https://doi.org/10.1111/j.1471-4159.2004.02879.x
  19. Landfield PW, Waymire JC, Lynch G. (1978). Hippocampal aging and adrenocorticoids: quantitative correlations. Science 202: 1098-1102 https://doi.org/10.1126/science.715460
  20. Lee PR, Brady D, Koenig JI. (2003). Thyroid hormone regulation of N-methyl-D-aspartic acid receptor subunit mRNA expression in adult brain. J Neuroendocrinol 15: 87-92 https://doi.org/10.1046/j.1365-2826.2003.00959.x
  21. Magarinos AM, McEwen BS. (2000). Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc Natl Acad Sci USA 97: 11056-11061 https://doi.org/10.1073/pnas.97.20.11056
  22. Matsushita M, Tamura K, Osada S, Kogo H. (2005). Effect of troglitazone on the excess testosterone and LH secretion in thyroidectomized, insulin-resistant, type 2 diabetic Goto-Kakizaki rats. Endocrine 27: 301-305 https://doi.org/10.1385/ENDO:27:3:301
  23. Mennemeier M, Garner RD, Heilman KM. (1993). Memory, mood and measurement in hypothyroidism. J Clin Exp Neuropsychol 15: 822-831 https://doi.org/10.1080/01688639308402598
  24. Montaron MF, Drapeau E, Dupret D, et al. (2006). Lifelong corticosterone level determines age-related decline in neurogenesis and memory. Neurobiol Aging 27: 645-654 https://doi.org/10.1016/j.neurobiolaging.2005.02.014
  25. Montero-Pedrazuela A, Venero C, Lavado-Autric R, et al. (2006). Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior. Mol Psychiatry 11: 361-671 https://doi.org/10.1038/sj.mp.4001802
  26. Narayanan CH, Narayanan Y. (1985). Cell formation in the motor nucleus and mesencephalic nucleus of the trigeminal nerve of rats made hypothyroid by propylthiouracil. Exp Brain Res 59: 257-266
  27. Patel AJ, Hayashi M, Hunt A. (1987). Selective persistent reduction in choline acetyltransferase activity in basal forebrain of the rat after thyroid deficiency during early life. Brain Res 422: 182-185 https://doi.org/10.1016/0006-8993(87)90556-7
  28. Paxinos G, Watson C. (2007). The rat brain in stereotaxic coordinates. Amsterdam, Elsevier Academic Press.
  29. Piroli GG, Grillo CA, Reznikov LR, et al. (2007). Corticosterone impairs insulin-stimulated translocation of GLUT4 in the rat hippocampus. Neuroendocrinology 85: 71-80 https://doi.org/10.1159/000101694
  30. Ryan CM, Geckle MO. (2000). Circumscribed cognitive dysfunction in middle-aged adults with type 2 diabetes. Diabetes Care 23: 1486-1493 https://doi.org/10.2337/diacare.23.10.1486
  31. Silva JE, Bianco SD. (2008). Thyroid-adrenergic interactions: physiological and clinical implications. Thyroid 18: 157-165 https://doi.org/10.1089/thy.2007.0252
  32. Siwak-Tapp CT, Head E, Muggenburg BA, Milgram NW, Cotman CW. (2007). Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive function. Neurobiol Learn Mem 88: 249-259 https://doi.org/10.1016/j.nlm.2007.05.001
  33. Smith JW, Evans AT, Costall B, Smythe JW. (2002). Thyroid hormones, brain function and cognition: a brief review. Neurosci Biobehav Rev 26: 45-60. https://doi.org/10.1016/S0149-7634(01)00037-9
  34. Song HJ, Stevens CF, Gage FH. (2002). Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat Neurosci 5: 438-445 https://doi.org/10.1038/nn844
  35. Stanfield BB, Trice JE. (1988). Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections. Exp Brain Res 72: 399-406
  36. Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP. (2008). Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci 11: 309-317 https://doi.org/10.1038/nn2055
  37. Tamura K, Osada S, Matsushita M, Abe K, Kogo H. (2005). Changes in ovarian steroidogenesis in insulin-resistant, type 2 diabetic Goto-Kakizaki rats after thyroidectomy and gonadotropin treatment. Eur J Pharmacol 513: 151-157 https://doi.org/10.1016/j.ejphar.2005.02.048
  38. Tohei A. (2004). Studies on the functional relationship between thyroid, adrenal and gonadal hormones. J Reprod Dev 50: 9-20 https://doi.org/10.1262/jrd.50.9
  39. Tohei A, Akai M, Tomabechi T, Mamada M, Taya K. (1997). Adrenal and gonadal function in hypothyroid adult male rats. J Endocrinol 152: 147-154 https://doi.org/10.1677/joe.0.1520147
  40. Tohei A, Imai A, Watanabe G, Taya K. (1998). Influence of thiouracil-induced hypothyroidism on adrenal and gonadal functions in adult female rats. J Vet Med Sci 60: 439-446 https://doi.org/10.1292/jvms.60.439
  41. Trudeau F, Gagnon S, Massicotte G. (2004). Hippocampal synaptic plasticity and glutamate receptor regulation: influences of diabetes mellitus. Eur J Pharmacol 490: 177-186 https://doi.org/10.1016/j.ejphar.2004.02.055
  42. Watts LM, Manchem VP, Leedom TA, et al. (2005). Reduction of hepatic and adipose tissue glucocorticoid receptor expression with antisense oligonucleotides improves hyperglycemia and hyperlipidemia in diabetic rodents without causing systemic glucocorticoid antagonism. Diabetes 54: 1846-1853 https://doi.org/10.2337/diabetes.54.6.1846
  43. Weng Q, Saita E, Watanabe G, et al. (2007). Effect of methimazole-induced hypothyroidism on adrenal and gonadal functions in male Japanese quail (Coturnix japonica). J Reprod Dev 53: 1335-1341 https://doi.org/10.1262/jrd.19081
  44. Wilcoxon JS, Nadolski GJ, Samarut J, Chassande O, Redei EE. (2007). Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha. Behav Brain Res 177: 109-116 https://doi.org/10.1016/j.bbr.2006.10.030
  45. Williams GR. (2008). Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol 20: 784-794 https://doi.org/10.1111/j.1365-2826.2008.01733.x
  46. Zucker LM, Zucker TF. (1961). Fatty, a new mutation in the rat. J Hered 52: 275-278 https://doi.org/10.1093/oxfordjournals.jhered.a107093

Cited by

  1. Suppressive effects of the peel of Citrus kawachiensis (Kawachi Bankan) on astroglial activation, tau phosphorylation, and inhibition of neurogenesis in the hippocampus of type 2 diabetic db/db mice vol.82, pp.8, 2010, https://doi.org/10.1080/09168451.2018.1469396
  2. Inhibitory Effects of Auraptene and Naringin on Astroglial Activation, Tau Hyperphosphorylation, and Suppression of Neurogenesis in the Hippocampus of Streptozotocin-Induced Hyperglycemic Mice vol.7, pp.8, 2018, https://doi.org/10.3390/antiox7080109
  3. Inducible nitric oxide synthase inhibitor, aminoguanidine improved Ki67 as a marker of neurogenesis and learning and memory in juvenile hypothyroid rats vol.80, pp.5, 2020, https://doi.org/10.1002/jdn.10042