Skip to main content

Advertisement

SpringerLink
Log in

Peripheral and central administration of T3 improved the histological changes, memory and the dentate gyrus electrophysiological activity in an animal model of Alzheimer’s disease

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

The amyloid beta (Aβ) induced Alzheimer’s disease (AD) is associated with formation the amyloid plaques, cognitive impairments and decline in spontaneous discharge of neurons. In the current study, we evaluated the effect of subcutaneous (S. C) and intrahippocampal (I. H) administrations of triiodothyronine (T3) on the histological changes, memory and the dentate gyrus (DG) electrophysiological activity in an animal model of AD. Eighty adult male Wistar rats (250–300 g) were divided randomly into five groups: Sham-Operated (Sh-O), AD + Vehicle (S. C), AD + Vehicle (I. H), AD+ T3 (S. C) and AD + T3 (I. H). In order to induce animal model of AD, Aβ (10 ng/μl, bilaterally) were injected intrahippocampally. Rats were treated with T3 and/or normal saline for 10 days. Passive avoidance and spatial memory were evaluated in shuttle box apparatus and Morris water maze, respectively. Neuronal single unit recording was assessed from hippocampal DG. The percent of total time that animals spent in target quarter, the mean latency time (sec), the step through latency and the average number of spikes/bin were decreased significantly in AD rats compared with the Sh-O group (p < 0.001) and were increased significantly in AD groups that have received T3 (S. C and I. H) in compared with AD group (p < 0.01, p < 0.001). Also, formation of amyloid plaques was decreased in AD rats treated with T3.

The results showed that T3 injection (S. C and I. H), by reduction of neural damage and increment of neuronal spontaneous activity improved the memory deficits in Aβ-induced AD rats.

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
Fig. 5

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

I.H:

Intrahippocampally

T3:

Triiodothyronine

S.C:

Subcutaneously

PAT:

Passive avoidance task

MWM:

Morris water maze

References

  • Bastianetto S, Yao ZX, Papadopoulos V, Quirion R (2006) Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci 23:55–64. doi:10.1111/j.1460-9568.2005.04532.x

    Article  PubMed  Google Scholar 

  • Bauer M, Goetz T, Glenn T, Whybrow PC (2008) The thyroid-brain interaction in thyroid disorders and mood disorders. J Neuroendocrinol 20:1101–1114. doi:10.1111/j.1365-2826.2008.01774.x

    Article  CAS  PubMed  Google Scholar 

  • Bunevicius R (2009) Thyroid disorders in mental patients. Curr Opin Psychiatry 22:391–395. doi:10.1097/YCO.0b013e328329e1ae

    Article  PubMed  Google Scholar 

  • Cao X, Kambe F, Yamauchi M, Seo H (2009) Thyroid-hormone-dependent activation of the phosphoinositide 3kinase/Akt cascade requires Src and enhances neuronal survival. Biochm J 424:201–209. doi:10.1042/BJ20090643

    Article  CAS  Google Scholar 

  • Cao JH, Lin HY, Davis FB, Zhou M, Davis PJ (2011) L-thyroxine attenuates pyramidal neuron excitability in rat acute prefrontal cortex slices. Immunol Endocrine & Metabolic Agents in Medicinal Chemistry 11:152–156. doi:10.2174/18715221179 6642828

    Article  CAS  Google Scholar 

  • Caria MA, Dratman MB, Kow OM, Pavlide C (2008) Thyroid hormone action: Nongenomic modulation of neuronal excitibiliy in the hippocampus. J neurendocrin 21:98–107. doi:10.1111/j.1365-2826.2008.01813.x

    Article  Google Scholar 

  • Chen QS, Kagan BL, Hirakura Y, Xie CW (2000) Impairment of hippocampal long-term potentiation by Alzheimer amyloid beta-peptides. J Neurosci Res 60:65–72

    Article  CAS  PubMed  Google Scholar 

  • Contreras-Jurado C, Pascual A (2012) Thyroid hormone regulation of APP (β-amyloid precursor protein) gene expression in brain and brain cultured cells. Neurochem Int 60:484–487. doi:10.1016/j.neuint.2012.01.027

    Article  CAS  PubMed  Google Scholar 

  • Darras VM, Van Herck SL, Geysens S, Reyns GE (2009) Involvement of thyroid hormones in chicken embryonic brain development. Gen Comp Endocrinol 163:58–62. doi:10.1016/j. ygcen.2008.11.014

    Article  CAS  PubMed  Google Scholar 

  • Davidoff RA, Ruskin HM (1972) The effects of microelectrophoretically applied thyroid hormone on single cat central nervous system neurons. Neurology 22:467–472

    Article  CAS  PubMed  Google Scholar 

  • Davis JD, Podolanczuk A, Donahue JE, Stopa E, Hennessey JV, Luo LG, Lim YP, Stern RA (2008) Thyroid hormone levels in the prefrontal cortex of post-mortem brains of alzheimer’s disease patients. Curr Aging Sci 1:175–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Disterhoft JF, Oh MM (2007) Alterations in intrinsic neuronal excitability during normal aging. Aging Cell 6:327–336. doi:10.1111/j.1474-9726.2007.00297.x

    Article  CAS  PubMed  Google Scholar 

  • Disterhoft JF, Wu WW, Ohno M (2004) Biophysical alterations of hippocampal pyramidal neurons in learning, ageing and Alzheimer’s disease. Ageing Res Rev 3:383–406. doi:10.1016/j.arr.2004.07.001

    Article  PubMed  Google Scholar 

  • Doulah AH, Rohani AH, Khaksari Haddad M, Motamedi F, Farbood Y, Badavi M, Malek M, Sarkaki A (2009) The effect of peripheral administration of growth hormone on AD-like cognitive deficiency in NBM-lesioned rats. Neurosci Lett 466:47–51. doi:10.1016/j.neulet.2009.09.016

    Article  CAS  PubMed  Google Scholar 

  • Ehrlich D, Hochstrasser T, Humpel C (2013) Effects of oxidative stress on amyloid precursor protein processing in rat and human platelets. Platelets 24:26–36. doi:10.3109/095 37104.2012.661104

    Article  CAS  PubMed  Google Scholar 

  • Esfandiary E, Karimipour M, Mardani M, Ghanadian M, Alaei HA, Mohammadnejad D, Esmaeili A (2015) Neuroprotective effects of Rosa Damascena extract on learning and memory in a rat model of amyloid-β induced Alzheimer’s disease. Adv Biomed Res 4:131. doi:10.4103/2277-9175.161512

    Article  PubMed  PubMed Central  Google Scholar 

  • Farbood Y, Sarkaki A, Badavi M (2009) Preventive effect of grape seed hydroalcholic extract on dementia type of Alzheimer’s disease in aged male rats. Int J Pharmacol 5:257–262

    Article  CAS  Google Scholar 

  • Ferreiro E, Baldeiras I, Ferreira IL, Costa RO, Rego AC, Pereira CF, Oliveira CR (2012) Mitochondrial and endoplasmic reticulum-associated oxidative stress in Alzheimer’s disease: from pathogenesis to biomarkers. Int J Cell Biol 2012:735206. doi:10.1155/2012/735206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haghparast A, Semnanian S, Fathollahi Y (1998) Morphine tolerance and dependence in the nucleus paragigantocellularis: single unit recording study in vivo. Brain Res 814:71–77

    Article  CAS  PubMed  Google Scholar 

  • Henry W, Querfurth HW, LaFerla FM (2010) Mechanisms of disease Alzheimer’s disease. N Engl J Med 362:329–344

    Article  Google Scholar 

  • Hoffmann G, Dietzel ID (2004) Thyroid hormone regulates excitability in central neurons from postnatal rats. Neurosci 125:369–379. doi:10.1016/j.neuroscience.2004.01.047

    Article  CAS  Google Scholar 

  • Horsten GP, Boeles JT (1949) The influence of hypothyroidism on the excitability of peripheral nerves. Arch Int Pharmacodyn 78:93–99

    CAS  PubMed  Google Scholar 

  • Kahaly G, Tettenborn B, Mihaljevic V, Beyer J, Krämer G (1989) Petit-mal-Status bei Hyperthyreose. DMW - Deutsche Medizinische Wochenschrift 114 (42):1607–1611. doi:10.1055/s-2008-1066803

  • Kelly BL, Ferreira A (2006) β-amyloid-induced dynamin 1 degradation is mediated by N-methyl-D-aspartate receptors in hippocampal neurons. J Biol Chem 281:28079–28089. doi:10.1074/jbc.M605081200

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1046/j.1365-2826.2003.00959.x

    Article  CAS  PubMed  Google Scholar 

  • Liang C, Tan S, Huang Q, Lin G, Lu Z, Lin X (2015) Prantensien ameliorates β-amyloid-induced cognitive impairment in rats via reducing oxidative damage and restoring synapses and BDNF levels. Neurosci Lett 592:48–53. doi:10.1016/j.neulet.2015.03.003

  • Lifschytz T, Gur E, Lerer B, Newman ME (2004) Effects of triiodothyronine and fluoxetine on 5-HT1A and 5-HT1B autoreceptor activity in rat brain: regional differences. J Neurosci Methods 140:133–139. doi:10.1016/j.jneumeth.2004.03.028

    Article  CAS  PubMed  Google Scholar 

  • Lima FR, Gervais A, Colin C, Izembart M, Neto VM, Mallat M (2001) Regulation of microglial development: a novel role for thyroid hormone. J Neurosci 21:2028–2038

    CAS  PubMed  Google Scholar 

  • Liu P, Kemper LJ, Wang J, Zahs KR, Ashe KH, Pasinetti GM (2011) Grape seed polyphenolic extract specifically decreases abeta 56 in the brains of Tg2576 mice. J Alzheimers Dis 26:657–666. doi:10.3233/JAD-2011-110383

    CAS  PubMed  Google Scholar 

  • Maccioni RB, Munoz GP, Barbeito L (2001) The molecular bases of Alzheimer’s disease and other neurodegenerative disorders. Arch Med 32:367–381. doi:10.1016/S0188-4409 (01) 00316-2

    CAS  Google Scholar 

  • Makii EA, Nerush PA, Rodinskii AG, Myakoushko VA (2002) Evoked activity of afferent and efferent fibers of the sciatic nerve in rats under conditions of experimental hyperthyroidism. Neurophysiology 34:44–51. doi:10.1023/A:1020218008768

    Article  CAS  Google Scholar 

  • Mansouri MT, Farbood Y, Naghizadeh B, Shabani S, Mirshekar MA, Sarkaki A (2016) Beneficial effects of ellagic acid against animal models of scopolamine- and diazepam-induced cognitive impairments. Pharma Bio. doi:10.3109/13880209.2015.1137601

    Google Scholar 

  • Martin JV, Williams DB, Fitzgerald RM, Im HK, Vonvoigtlander PF (1996) Thyroid hormonal modulation of the binding and activity of the GABAA receptor complex of brain. Neuroscience 73:705–713. doi:10.1016/0306-4522(96)00052-8

    Article  CAS  PubMed  Google Scholar 

  • Mirakhur A, Craig D, Hart DJ, McLlroy SP, Passmore AP (2004) Behavioural and psychological syndromes in Alzheimer’s disease. Int J Geriatr Psychiatry 19(11):1035–1039. doi:10.1002/gps.1203

    Article  CAS  PubMed  Google Scholar 

  • Mooradian AD (1990) Blood-brain barrier transport of triiodothyronine is reduced in aged rats. Mech Ageing and Devel 52:141–147. doi:10.1016/0047-6374(90)90120-5

    Article  CAS  Google Scholar 

  • Ogino R, Murayama N, Noshita T, Takemoto N, Toba T, Oka T, Narii N, Yoshida S, Ueno N, Inoue T (2014) SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer’s disease induced by amyloid β and excitatory amino acids. Brain Res 1585:159–166. doi:10.1016/j.brain res.20 14.08.023

    Article  CAS  PubMed  Google Scholar 

  • Oguro K, Ito M, Tsuda H, Mutoh K, Shiraishi H, Shirasaka Y, Mikawa H (1989) Interaction of thyroid hormones with L-(3H) glutamate binding sites, with special reference to N-methyl-D-aspartate receptors. Res Commun Chem Pathol Pharmacol n 65:181–196

    CAS  Google Scholar 

  • Oshima K, Gorbman A (1996) Influence of thyroxine and steroid hormones on spontaneous and evoked unitary activity in the olfactory bulb of goldfish. Gen Comp Endocrinol 7:482–491. doi:10.1016/0016-6480(66)90070-0

    Article  Google Scholar 

  • Pan Y-F, Jia X-T, Wang X-H, Chen X-R, Li Q-S, Gao X-P, Qi J-S (2013) Arginine vasopressin remolds the spontaneous discharges disturbed by amyloid β protein in hippocampal CA1 region of rats. Regulatory Peptides 183:7–12

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic Coordinatesedn. Academic Press, New York

    Google Scholar 

  • Radetti G, Dordi B, Mengarda G, Biscaldi I, Larizza D, Severi F (1993) Thyrotoxicosis presenting with seizures and coma in two children. Am J Dis Child 147:925–927. doi:10.1001/archpedi.1993.02160330015002

    CAS  PubMed  Google Scholar 

  • Robins Wahlin TB, Byrne GJ (2011) Personality changes in Alzheimer’s disease: a systematic review. Int J Geriatr Psychiatry 26:1019–1029. doi:10.1002/gps.2655

    Article  PubMed  Google Scholar 

  • Sandrini M, Marrama D, Vergoni AV, Bertolini A (1992) Repeated administration of triiodothyronine enhances the susceptibility of rats to isoniazid- and picrotoxin-induced seizures. Life Sci 51:765–770. doi:10.1016/0024-3205(92)90486-9

    Article  CAS  PubMed  Google Scholar 

  • Sarkaki A, Badavi M, Aligholi H, Moghaddam AZ (2009) Preventive effects of soy meal (+/− isoflavone) on spatial cognitive deficiency and body weight in an ovariectomized animal model of Parkinson’s disease. Pak J Biol Sci 12:1338–1345

    Article  CAS  PubMed  Google Scholar 

  • Sarkaki A, Fathimoghaddam H, Mansouri SM, Korrani MS, Saki G, Farbood Y (2014) Gallic acid improves cognitive, hippocampal long-term potentiation deficits and brain damage induced by chronic cerebral Hypoperfusion in rats. Pak J Biol Sci 17(8):978–990. doi:10.3923/pjbs.2014.978-990

    Article  CAS  PubMed  Google Scholar 

  • Scuderi C, Stecca C, Bronzuoli MR, Rotili D, Valente S, Mai A, Steardo L (2014) Sirtuin modulators control reactive gliosis in an in vitro model of Alzheimer’s disease. Front Pharmacol 5:89. doi:10.3389/fphar.2014.00089

    Article  PubMed  PubMed Central  Google Scholar 

  • Sousa JC, Cardoso I, Marques F, Saraiva MJ, Palha JA (2007) Transthyretin and Alzheimer’s disease: where in the brain? Neurobiol Aging 28:713–718. doi:10.1016/j.neurobiolaging.2006.03.015

    Article  CAS  PubMed  Google Scholar 

  • Stenzel D, Huttner WB (2013) Role of maternal thyroid hormones in the developing neocortex and during human evolution. Front Neuroanat 7:1. doi:10.3389/fnana.2013.00019

    Article  Google Scholar 

  • Sui L, Wang J, Li BM (2008) Administration of Triiodo-L-thyronine into dorsal hippocampus alters phosphorylation of Akt, mammalian target of rapamycin, p70S6 kinase and 4E-BP1 in rats. Neurochem Res 33:1065–1076. doi:10.1007/s11064-007-9551-2

    Article  CAS  PubMed  Google Scholar 

  • Sui L, Ren WW, Li BM (2010) Administration of thyroid hormone increases reelin and brain-derived neurotrophic factor expression in rat hippocampus in vivo. Brain Res 1313:9–24. doi:10.1016/j.brainres.2009.12.010

    Article  CAS  PubMed  Google Scholar 

  • Swanson JW, Kelly JJ, McConahey WM (1981) Neurologic aspects of thyroid dysfunction. Mayo Clin Proc 56:504–512

    CAS  PubMed  Google Scholar 

  • Szegedi V, Juhasz G, Budai D, Penke B (2005) Divergent effects of Aβ1–42 on ionotropic glutamate receptor-mediated responses in CA1 neurons in vivo, brain. Res 1062:120–126. doi:10.1016/j.brainres.2005.09.014

    CAS  Google Scholar 

  • Taylor JP, Hardy J, Fischbeck KH (2002) Toxic proteins in neurodegenerative disease. Science 296:1991–1995. doi:10.1126/science.1067122

    Article  CAS  PubMed  Google Scholar 

  • Thomas DR, Hailwood R, Harris B, Williams PA, Scanlon MF, John R (1987) Thyroid status in senile dementia of the Alzheimer type (SDAT). Acta Psychiatr Scand 76:158–163

    Article  CAS  PubMed  Google Scholar 

  • Timiras PS, Woodbury DM, Agarwal SL (1955) Effect of thyroxine and triiodothyronine on brain function and electrolyte distribution in intact and adrenalectomized rats. J Pharmacol Exp Ther 115:154–171

    CAS  PubMed  Google Scholar 

  • Valizadeh Z, Eidi A, Sarkaki A, Farbood Y, Mortazavi P (2012) Dementia type of Alzheimer’s disease due to β-amyloid was improved by Gallic acid in rats. Health MED 6:3648. doi:10.15412/J.BCN.03070203

    Google Scholar 

  • Villette V, Poindessous-Jazat F, Simon A, Léna C, Roullot E, Bellessort B, Epelbaum J, Dutar P, Stéphan A (2010) Decreased rhythmic GABAergic septal activity and memory-associated θ oscillations after Hippocamp + al amyloid-β pathology in the rat. J Neurosci 30:10991–11003. doi:10.1523/JNEUROSCI.6284-09.2010

    Article  CAS  PubMed  Google Scholar 

  • Zare N, Khalifeh S, Khodagholi F, Zareh Shahamati S, Motamedi F, Maghsoudi N (2015) Geldanamycin reduces Aβ-associated anxiety and depression concurrent with autophagy provocation. J Mol Neurosci 57(3):317–324. doi:10.1007/s12031-015-0619-1

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This article was extracted as a part of Sahreh Shabani’s thesis (Ph. D student) and supported by research affairs of Ahvaz Jundishapur University of Medical Sciences (grant No. APRC-93-19) and was done in Ahvaz Physiology Research Center.

Author information

Authors and Affiliations

  1. Physiology Research Center, Department of Physiology, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Yaghoob Farbood, Sahreh Shabani, Alireza Sarkaki, Seyyed Ali Mard & Akram Ahangarpour

  2. Cellular and Molecular Research Center, Department of Anatomical Sciences, Medical School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Layasadat Khorsandi

Authors
  1. Yaghoob Farbood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sahreh Shabani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alireza Sarkaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seyyed Ali Mard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akram Ahangarpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Layasadat Khorsandi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yaghoob Farbood or Sahreh Shabani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Farbood, Y., Shabani, S., Sarkaki, A. et al. Peripheral and central administration of T3 improved the histological changes, memory and the dentate gyrus electrophysiological activity in an animal model of Alzheimer’s disease. Metab Brain Dis 32, 693–701 (2017). https://doi.org/10.1007/s11011-016-9947-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-016-9947-2

Keywords

Search

Navigation