Journal of Endocrinological Investigation

, Volume 31, Issue 1, pp 8–15 | Cite as

Effects of perinatal hypothyroidism on rat behavior and its relation with apoptosis of hippocampus neurons

  • X. W. Huang
  • H. M. Yin
  • C. Ji
  • Y. F. Qin
  • R. W. Yang
  • Z. Y. Zhao
Original Articles


Thyroid hormone is an important factor for proper development of the mammalian brain. Perinatal hypothyroidism leads to long-term behavior and neuromotor competence alterations in humans and animals. Our study aimed to investigate the effects of perinatal hypothyroidism on behavior changes of rat pups and its relation with the apoptosis of hippocampus neurons. Behavior tests were taken to evaluate the effects caused by perinatal hypothyroidism. TUNEL staining was used to analyze the apoptosis of neurons on CA3 region of hippocampus. The study suggested that perinatal hypothyroidism affects behavior development, as well as leading to the decrease in spatial learning and memory capability. This condition can be improved with hormone substitute treatment. Furthermore, the changes of learning and memory capability are closely related to the increasing number of apoptotic neurons in the hippocampus.


Perinatal hypothyroidism thyroid hormone brain behavior hippocampus 


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  1. 1.
    Koibuchi N, Jingu H, Iwasaki T, Chin WW. Current perspectives on the role of thyroid hormone in growth and development of cerebellum. Cerebellum 2003, 2: 279–89.PubMedCrossRefGoogle Scholar
  2. 2.
    Singh R, Upadhyay G, Godbole MM. Hypothyroidism alters mitochondrial morphology and induces release of apoptogenic proteins during rat cerebellar development. J Endocrinol 2003, 176: 321–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Kobayashi K, Tsuji R, Yoshioka T, et al. Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior and synaptic gene expression. Toxicology 2005, 212: 135–47.PubMedCrossRefGoogle Scholar
  4. 4.
    Davenport JW, Dorcey TP. Hypothyroidism: learning deficit induced in rats by early exposure to thiouracil. Hormon Behav 1972, 3: 97–112.CrossRefGoogle Scholar
  5. 5.
    Davenport JW, Gonzalez LM, Hennies RS, Hagquist WW. Severity and timing of early thyroid deficiency as factor in the induction of learning disorders in rats. Hormon Behav 1976, 7: 139–57.CrossRefGoogle Scholar
  6. 6.
    Eayrs JT. Influence of the thyroid on the central nervous system. Br Med Bull 1960, 16: 122–7.PubMedGoogle Scholar
  7. 7.
    Eayrs JT, Lishman WA. The maturation of behavior in hypothyroidism and starvation. Br J Anim Behav 1955, 3: 17–24.CrossRefGoogle Scholar
  8. 8.
    Darbra S, Balada F, Garau A, Gatell P, Sala J, Marti-Carbonell MA. Perinatal alterations of thyroid hormones and behaviour in adult rats. Behav Brain Res 1995, 68: 159–64.PubMedCrossRefGoogle Scholar
  9. 9.
    Darbra S, Garau A, Balada F, Sala J, Martí-Carbonell MA. Perinatal hypothyroidism effects on neuromotor competence, novelty-directed exploratory and anxiety-related behaviour and learning in rats. Behav Brain Res 2003, 143: 209–15.PubMedCrossRefGoogle Scholar
  10. 10.
    Bernal J. Action of thyroid hormone in brain. J Endocrinol Invest 2002, 25: 268–88.PubMedCrossRefGoogle Scholar
  11. 11.
    Koibuchi N, Fukuda H, Chin WW. Promoter-specific regulation of the brain-derived neurotropic factor gene by thyroid hormone in the developing rat cerebellum. Endocrinology 1999, 140: 3955–61.PubMedGoogle Scholar
  12. 12.
    Pombo PM, Barettino D, Ibarrola N, Vega S, Rodríguez-Peña A. Stimulation of the myelin basic protein gene expression by 9-cis-retinoic acid and thyroid hormone: activation in the context of its native promoter. Brain Res Mol Brain Res 1999, 64: 92–100.PubMedCrossRefGoogle Scholar
  13. 13.
    Dowling AL, Zoeller RT. Thyroid hormone of maternal origin regulates the expression of RC3/neurogranin mRNA in the fetal rat brain. Brain Res Mol Brain Res 2000, 82: 126–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Manzano J, Morte B, Scanlan TS, Bernal J. Differential effects of triiodothyronine and the thyroid hormone receptor beta-specific agonist GC-1 on thyroid hormone target genes in the brain. Endocrinology 2003, 144: 5480–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Cai D, Su Q, Chen Y, Luo M. Effect of thyroid hormone deficiency on developmental expression of goalpha gene in the brain of neonatal rats by competitive RT-PCR and in situ hybridization histochemistry. Brain Res 2000, 864: 195–204.PubMedCrossRefGoogle Scholar
  16. 16.
    White AM, Matthews DB, Best PJ. Ethanol, memory, and hippocampal function: a review of recent findings. Hippocampus 2000, 10: 88–93.PubMedCrossRefGoogle Scholar
  17. 17.
    Huang XW, Zhao ZY, Ji C. Effects of hypothyroidism on apoptosis and the expression of Bcl-2 and Bax gene in the neonatal rat hippocampus neurons. Zhonghua Er Ke Za Zhi 2005, 43: 48–52.PubMedGoogle Scholar
  18. 18.
    MacNabb C, O’Hare E, Cleary J, Georgopoulos AP. Congenital hypothyroidism impairs response alternation discrimination behavior. Brain Res 1999, 847: 231–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Chen Z, Zhao Q, Sugimoto Y, Fujii Y, Kamei C. Effects of histamine on MK-801-induced memory deficits in radial maze performance in rats. Brain Res 1999, 839: 186–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Nishiga M, Sugimoto Y, Taga C, Fujii Y, Kamei C. Effects of NMDA antagonist MK-801 on radial maze performance in histidine-deficient rats. Life Sci 2002, 70: 2199–208.PubMedCrossRefGoogle Scholar
  21. 21.
    Adams J, Buelke-Sam J, Kimmel CA, et al. Collaborative Behavioral Teratology Study: protocol design and testing procedures. Neurobehav Toxicol Teratol 1985, 7: 579–86.PubMedGoogle Scholar
  22. 22.
    Kalynchuk LE, Pinel J PJ, Treit D, Barnes SJ, McEachern JC, Kippin TE. Presistence of the interictal emotionality produced by long-term amygdala kindling in rats. Neuroscience 1998, 85: 1311–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Goldey ES, Kehn LS, Rehnberg GL, Crofton KM. Effects of developmental hypothyroidism on auditory and motor function in the rat. Toxicol Appl Pharmacol 1995, 135: 67–76.PubMedCrossRefGoogle Scholar
  24. 24.
    Vaccari A, Rossetti ZL, de Montis G, Stefanini E, Martino E, Gessa GL. Neonatal hypothyroidism induces striatal dopaminergic dysfunction. Neuroscience 1990, 35: 699–706.PubMedCrossRefGoogle Scholar
  25. 25.
    Sandrini M, Marrama D, Vergoni AV, Bertolini A. Effects of thyroid status on the characteristics of alpha 1-, alpha 2-, beta, imipramine and GABA receptors in the rat brain. Life Sci 1991, 48: 659–66.PubMedCrossRefGoogle Scholar
  26. 26.
    Thiel CM, Müller CP, Huston JP, Schwarting RK. High versus low reactivity to a novel environment: behavioural, pharmacological and neurochemical assessments. Neuroscience 1999, 93: 243–51.PubMedCrossRefGoogle Scholar
  27. 27.
    Chen Z, Shen Y J. Effects of histamine on memory deficit induced by nucleus basalis lesion on passive avoidance test and radialmaze performance in rats. Acta Pharmacol Sin 2002, 23: 66–70.PubMedGoogle Scholar
  28. 28.
    Chen Z, Sugimoto Y, Kamei C. Effects of intracerebroventricular injection of α-fluoromethylhistidine on radial maze performance in rats. Biochem Biochem Behav 1999, 64: 513–8.CrossRefGoogle Scholar
  29. 29.
    Lehmann J, Pryce CR, Bettschen D, Feldon J. The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats. Pharmacol Biochem Behav 1999, 64: 705–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Jarrard LE. On the role of the hippocampus in learning and memory in the rat. Behav Neural Biol 1993, 60: 9–26.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2008

Authors and Affiliations

  • X. W. Huang
    • 1
  • H. M. Yin
    • 2
  • C. Ji
    • 1
  • Y. F. Qin
    • 1
  • R. W. Yang
    • 1
  • Z. Y. Zhao
    • 1
  1. 1.Department of Child HealthZhejiang University, School of Medicine Associated Children’s HospitalHangzhouChina
  2. 2.Department of NeurosurgeryFuyang Renmin HospitalHangzhouChina

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