Skip to main content
SpringerLink
Log in

Effect of persistent and transient hypothyroidism on histoarchitecture and antioxidant defence system in rat brain

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

The present study reports the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameter, lipid peroxidation (LPx) and major antioxidant enzyme expressions such as superoxide dismutase (SOD: SOD1 and SOD2) and catalase (CAT) in cerebral cortex rat brain during postnatal persistent (90 days PTU treatment from birth) and transient (30 days PTU treatment from birth followed by PTU withdrawal for 60 days) hypothyroidism. Enhanced level of LPx was observed in transient hypothyroid rats with respect to control and persistent hypothyroid rats. Significantly increased activity of SOD and expression of SOD1 were observed in cerebral cortex of both persistent and transient hypothyroid rats as compared to control. However, unaltered translated level of SOD2 was observed among the groups. Activity of CAT was increased in transient hypothyroid rats, whereas translate level of CAT was increased in both the regions of persistent as well as transient hypothyroidism. The histoarchitecture of cerebral cortex clearly showed a decline in neuronal migration with neurons packed together in both persistent and transient hypothyroid rats as compared to control. These results suggest that deprivation of thyroid hormone modulates redox status and causes oxidative stress in rat brain cerebral cortex during postnatal development and maturation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Oppenheimer JH, Schwartz HL (1997) Molecular basis of thyroid hormone-dependent brain development. Endocr Rev 18:462–475

    CAS  PubMed  Google Scholar 

  2. Ahmed OM, El-Gareib AW, El-bakry AM, Abd El-Tawab SM, Ahmed RG (2008) Thyroid hormones states and brain development interactions. Int J Devl Neurosci 26:147–2095

    Article  CAS  Google Scholar 

  3. Porterfield SP, Hendrich CE (1993) The role of thyroid hormones in prenatal and neonatal neurological development-current perspectives. Endocr Rev 14:94–106

    CAS  PubMed  Google Scholar 

  4. Guerrero A, Pamplona R, Porter-Otin M, Barja G, Lopez-Torres M (1999) Effect of thyroid status on lipid composition and peroxidation in the mouse liver. Free Rad Biol Med 26:73–80

    Article  CAS  PubMed  Google Scholar 

  5. Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134:707–716

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Halliwell B, Gutteridge JMC (2001) In Free Radicals in Biology and Medicine, 3rd edn. Oxford University Press, New York

    Google Scholar 

  7. Zoeller RT, Crofton KM (2005) Mode of action: developmental thyroid hormone insufficiency-Neurological abnormalities resulting from exposure to propylthiouracil. Critical Rev Toxicol 35:771–781

    Article  CAS  Google Scholar 

  8. Ahmed OM, El-Gareib AW, El-bakry AM, Abd El-Tawab SM, Ahmed RG (2008) Thyroid hormones states and brain development interactions. Int J Dev Neurosci 26:147–209

    Article  CAS  PubMed  Google Scholar 

  9. Bhanja S, Chainy GBN (2010) PTU-induced hypothyroidism modulates antioxidant defence status in the developing cerebellum. Int J Dev Neurosci 28:251–262

    Article  CAS  PubMed  Google Scholar 

  10. Bhanja S, Jena S (2013) Modulation of antioxidant enzyme expression by PTU-induced hypothyroidism in cerebral cortex of postnatal rat brain. Neurochem Res 38:42–49

    Article  CAS  PubMed  Google Scholar 

  11. Jena S, Chainy GBN, Dandapat J (2012) Modulation of renal antioxidant enzymes expression by PTU-induced hypothyroidism during postnatal development and maturation. Gen Comp Endocrinol 178:8–18

    Article  CAS  PubMed  Google Scholar 

  12. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:352–358

    Article  Google Scholar 

  13. Das K, Samanta L, Chainy GBN (2000) A modified spectrophotometric assay of superoxide dismutase using nitrite formation of superoxide radicals. Indian J Biochem Biophys 37:201–204

    CAS  Google Scholar 

  14. Cohen G, Dembiec D, Marcus J (1970) Measurement of catalase activity in tissue extracts. Anal Biochem 34:30–38

    Article  CAS  PubMed  Google Scholar 

  15. Aebi H (1974) Catalase. In: Bergmayer HU (ed) Methods of enzymatic analysis, vol II. Academic Press, New York, pp 673–683

    Chapter  Google Scholar 

  16. Cao XY, Jiang XM, Dou ZH, Murdon AR, Zhang ML, O’Donnell K, Ma T, Kareem A, DeLong N, Delong GR (1994) Timing of vulnerability of the brain to iodine deficiency in endemic cretinism. New Engl J Med 331:1739–1744

    Article  CAS  PubMed  Google Scholar 

  17. Alzoubi KH, Gerges NZ, Aleisa AM, Alkadhi KA (2009) Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: behavioral, electrophysiological, and molecular studies. Hippocampus 19:66–78

    Article  CAS  PubMed  Google Scholar 

  18. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 93:2696–2701

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Springer JE, Azbill RD, Mark RJ, Begley JG, Waeg G, Mattson MP (1997) 4-Hydroxynonenal, a lipid peroxidation product, rapidly accumulates following spinal cord injury and inhibits glutamate uptake. J Neurochem 68:2469–2476

    Article  CAS  PubMed  Google Scholar 

  20. Lovell MA, Ehmann WD, Mattson MP, Markesbery WR (1997) Elevated 4-hydroxynonenal in ventricular fluid in Alzheimer’s disease. Neurobiol Aging 18:457–461

    Article  CAS  PubMed  Google Scholar 

  21. Mogulkoc R, Baltaci AK, Aydin L, Oztekin E, Sivrikaya A (2005) The effect of thyroxine administration on lipid peroxidation in different tissues of rats with hypothyroidism. Acta Physiol Hung 92:39–46

    Article  CAS  PubMed  Google Scholar 

  22. Yilmaz S, Ozan S, Benzer F, Canatan H (2003) Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism. Cell Biochem Funct 21:325–330

    Article  CAS  PubMed  Google Scholar 

  23. Jena S, Anand C, Chainy GBN, Dandapat J (2012) Induction of oxidative stress and inhibition of superoxide dismutase expression in rat cerebral cortex and cerebellum by PTU-induced hypothyroidism and its reversal by curcumin. Neurol Sci 33:869–873

    Article  PubMed  Google Scholar 

  24. Jena S, Bhanja S (2014) Hypothyroidism alters antioxidant defence system in rat brainstem during postnatal development and adulthood. Neurol Sci 35:1269–1274

    Article  PubMed  Google Scholar 

  25. Cano-Europa E, Pe´rez-Severiano F, Vergara P, Ortiz-Butro´n R, Rı´os C, Segovia J, Pacheco-Rosado J (2008) Hypothyroidism induces selective oxidative stress in amygdala and hippocampus of rat. Metab Brain Dis 23:275–287

    Article  CAS  PubMed  Google Scholar 

  26. Das K, Chainy GBN (2004) Thyroid hormone influences antioxidant defence in adult rat brain. Neurochem Res 29:1755–1766

    Article  CAS  PubMed  Google Scholar 

  27. Rahaman SO, Ghosh S, Mohanakumar KP, Das S, Sarkar PK (2001) Hypothyroidism in the developing rat brain is associated with marked oxidative stress and aberrant intraneuronal accumulation of neurofilaments. Neurosci Res 40:273–279

    Article  CAS  PubMed  Google Scholar 

  28. Sen CK, Packer L (1996) Antioxidant and redox regulation of gene transcription. FASEB J 10:709–720

    CAS  PubMed  Google Scholar 

  29. Chiarugi P, Fiaschi T (2007) Redox signalling in anchorage-dependent cell growth. Cell Signal 19(4):672–682

    Article  CAS  PubMed  Google Scholar 

  30. Rojo AI, Salinas M, Martı´n D, Perona R, Cuadrado A (2004) Regulation of Cu/Zn-Superoxide dismutase expression via the phosphatidylinositol-3 kinase/Akt pathway and nuclear factor-κB. J Neurosci 24:7324–7334

    Article  CAS  PubMed  Google Scholar 

  31. Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419:316–321

    Article  CAS  PubMed  Google Scholar 

  32. Koibuchi N, Chin WW (2000) Thyroid hormone action and brain development. Trends Endocrinol Metab 11:123–128

    Article  CAS  PubMed  Google Scholar 

  33. Gilbert ME, Paczkowski C (2003) Propylthiouracil (PTU)-induced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus. Brain Res Dev Brain Res 145:19–29

    Article  CAS  PubMed  Google Scholar 

  34. Gilbert ME (2011) Impact of low-level thyroid hormone disruption induced by propylthiouracil on brain development and function. Toxicol Sci 124:432–445

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author is very thankful to the Department of Science and Technology (DST), Government of India, for the financial supports to carry out this work under the Grants of DST-Promotion of University Research and Scientific Excellence (PURSE) programme (DST Grant No. SR/S9/Z-23/2010/27)). The author is also extremely grateful to Prof. G.B.N. Chainy (UGC-Emeritus fellow) and Dr. J. Dandapat, Head, Department of Biotechnology, Utkal University, Bhubaneswar, Odisha, India, for extending laboratory facilities and supporting the author throughout the tenure of the work.

Conflict of interest

The author declares that there is no conflict of interest.

Author information

Author notes

  1. Srikanta Jena

    Present address: Department of Zoology, Ravenshaw University, Cuttack, 753003, Odisha, India

Authors and Affiliations

  1. Department of Biotechnology, Utkal University, Bhubaneswar, 751004, Odisha, India

    Srikanta Jena

Authors
  1. Srikanta Jena
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srikanta Jena.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jena, S. Effect of persistent and transient hypothyroidism on histoarchitecture and antioxidant defence system in rat brain. Neurol Sci 36, 953–959 (2015). https://doi.org/10.1007/s10072-015-2199-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-015-2199-9

Keywords

Search

Navigation