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Horm Metab Res 2001; 33(5): 270-275
DOI: 10.1055/s-2001-15120
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© Georg Thieme Verlag Stuttgart · New York

Involvement of L-Triiodothyronine in Acetylcholine Metabolism in Adult Rat Cerebrocortical Synaptosomes

P. K. Sarkar 1, 2 , A. K. Ray 2
  • 1 Department of Biology, Rutgers University, Camden, New Jersey USA
  • 2 Department of Animal Physiology, Bose Institute, Calcutta India
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Publication History

Publication Date:
31 December 2001 (online)

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Despite the recently emerging notion of thyroid-hormone involvement in neurotransmission in the adult mammalian brain, adequate evidence for a cellular basis of the process is still lacking. The present study indicates the involvement of thyroid hormones in cholinergic system of the adult rat cerebral cortex. Administration of L-triiodothyronine (T3, 0.025 to 4 µg/g) in single doses increased the synaptosomal acetylcholinesterase (AchE) and Mg2+-ATPase activity maximally at 24 hours in a dose-dependent way. Propylthiouracil (PTU)-treated hypothyroid rats showed a significant increase in AchE and Mg2+-ATPase activity compared to euthyroid rats. T3-treatment on hypothyroid rats decreased AchE activity in synaptosomes compared to the hypothyroid synaptosomal values. Mg2+-ATPase activity found in (PTU + T3)-treated group and T3-treated group remained high. These results predict that T3 stimulates acetylcholine (Ach) metabolism by increasing AchE activity as well as uptake of the released Ach through an increase in synaptosomal Mg2+-ATPase activity. This indicates a positive impact of T3 on the cholinergic system in the adult mammalian brain.

Key words:

Triiodothyronine - Adult Rat Brain - Synaptosomes - Hypothyroid - Acetylcholinesterase - Mg2+-ATPase

References

  • 1 Oppenheimer J H. Evolving concepts of thyroid hormone action.  Biochimie. 1999;  81 539-543
    CrossrefPubMedGoogle Scholar
  • 2 Dussault J H, Ruel J. Thyroid hormones and brain development.  Annu Rev Physiol. 1987;  49 321-334
    CrossrefPubMedGoogle Scholar
  • 3 Moskovkin G N, Kalman M, Kardos J, Yarigin K N, Hajos F. Effect of triiodothyronine on the muscarinic receptors and acetylcholinesterase activity of developing rat brain.  Int J Neurosci. 1989;  44 83-89
    PubMedGoogle Scholar
  • 4 Provost T L, Juarez de Ku L M, Zender C, Meserve L A. Dose- and age-dependent alterations in choline acetyltransferase (ChAT) activity, learning and memory, and thyroid hormones in 15- and 30-day old rats exposed to 1.25 or 12.5 PPM polychlorinated biphenyl (PCB) beginning at conception.  Prog Neuropsychopharmacol Biol Psychiatry. 1999;  23 915-928
    CrossrefPubMedGoogle Scholar
  • 5 Atterwill C K, Kingsbury A K, Nicholls J, Prince A. Development of markers for cholinergic neurones in re-aggregate cultures of foetal rat whole brain in serum-containing and serum-free media: effects of triiodothyronine (T3).  Br J Pharmacol. 1984;  83 89-102
    PubMedGoogle Scholar
  • 6 Juarez de Ku L M, Sharma-Stokkermans M, Meserve L A. Thyroxine normalizes polychlorinated biphenyl (PCB) dose-related depression of choline acetyltransferase (ChAT) activity in hippocampus and basal forebrain of 15-day-old rats.  Toxicology. 1994;  94 19-30
    CrossrefPubMedGoogle Scholar
  • 7 Landa M E, Gonzalez Burgos G, Cardinali D P. In vitro effect of thyroxine on cholinergic neurotransmission in rat sympathetic superior cervical ganglion.  Neuroendocrinology. 1991;  54 552-558
    PubMedGoogle Scholar
  • 8 Patel A J, Smith R M, Kingsbury A E, Hunt A, Balazs R. Effects of thyroid state on brain development: muscarinic acetylcholine and GABA receptors.  Brain Res. 1980;  198 389-402
    CrossrefPubMedGoogle Scholar
  • 9 Oppenheimer J H. Thyroid hormone action at the cellular level.  Science. 1979;  203 971-979
    PubMedGoogle Scholar
  • 10 Henley W N, Koehnle T J. Thyroid hormones and the treatment of depression: an examination of basic hormonal actions in the mature mammalian brain.  Synapse. 1997;  27 36-44
    CrossrefPubMedGoogle Scholar
  • 11 Dratman M B, Gordon J T. Thyroid hormones as neurotransmitters.  Thyroid. 1996;  6 639-647
    PubMedGoogle Scholar
  • 12 Mashio Y, Inada M, Tanaka K, Ishii H, Naito K, Nishikawa M, Takahashi K, Imura H. Synaptosomal T3 binding sites in rat brain: their localization on synaptic membrane and regional distribution.  Acta Endocrinol (Copenh). 1983;  104 134-138
    PubMedGoogle Scholar
  • 13 Sarkar P K, Ray A K. Specific binding of L-triiodothyronine modulates Na+-K+-ATPase activity in adult rat cerebrocortical synaptosomes.  Neuroreport. 1998;  9 1149-1152
    PubMedGoogle Scholar
  • 14 Sarkar P K, Ray A K. Synaptosomal T3 content in cerebral cortex of adult rat in different thyroidal states.  Neuropsychopharmacology. 1994;  11 151-155
    CrossrefPubMedGoogle Scholar
  • 15 Thomas D R, Hailwood R, Harris B, Williams P A, Scanlon M F, John R. Thyroid status in senile dementia of the Alzheimer type (SDAT).  Acta Psychiatr Scand. 1987;  76 158-163
    PubMedGoogle Scholar
  • 16 Fylkesnes S I, Nygaard H A. Dementia and hypothyroidism.  Tidsskr Nor Laegeforen. 2000;  120 905-907
    PubMedGoogle Scholar
  • 17 Foley P B, Crocker A D. Dopamine agonist-mediated inhibition of acetylcholine release in rat striatum is modified by thyroid hormone status.  J Neurochem. 1993;  61 812-817
    PubMedGoogle Scholar
  • 18 Ahmed M T, Sinha A K, Pickard M R, Kim K D, Ekins R P. Hypothyroidism in the adult rat causes brain region-specific biochemical dysfunction.  J Endocrinol. 1993;  138 299-305
    PubMedGoogle Scholar
  • 19 Salvati S, Attorri L, Campeggi L M, Olivieri A, Sorcini M, Fortuna S, Pintor A. Effect of propylthiouracil-induced hypothyroidism on cerebral cortex of young and aged rats: lipid composition of synaptosomes, muscarinic receptor sites, and acetylcholinesterase activity.  Neurochem Res. 1994;  19 1181-1186
    CrossrefPubMedGoogle Scholar
  • 20 Haigh J R, Noremberg K, Parsons S M. Acetylcholine active transport by rat brain synaptic vesicles.  Neuroreport. 1994;  5 773-776
    PubMedGoogle Scholar
  • 21 Ellman G L, Courtney K D, Andres V Jr, Featherstone R M. A new and rapid colorimetric determination of acetylcholinesterase activity.  Biochem Pharmacol. 1961;  7 88-95
    CrossrefPubMedGoogle Scholar
  • 22 Sarkar P K, Ray A K. Synaptosomal action of thyroid hormone: changes in Na+-K+-ATPase activity in adult rat cerebral cortex.  Horm Metab Res. 1993;  25 1-3
    PubMedGoogle Scholar
  • 23 Vera J C. Measurement of microgram quantities of protein by a generally applicable turbidimetric procedure.  Anal Biochem. 1988;  174 187-196
    CrossrefPubMedGoogle Scholar
  • 24 De S, Ray A K, Medda A K. Demonstration of hepatic cytosolic malic enzyme activity as a thyroid hormone sensitive physiologic parameter in a teleost, Heteropneustes fossilis bloch.  Horm Metab Res. 1988;  20 213-217
    PubMedGoogle Scholar
  • 25 Crantz F R, Silva J E, Larsen P R. An analysis of the sources and quantity of 3,5,3’-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum.  Endocrinology. 1982;  110 367-375
    CrossrefPubMedGoogle Scholar
  • 26 Escobar del Rey F, Ruiz de Ona C, Bernal J, Obregon M J, Morreale de Escobar G. Generalized deficiency of 3,5,3’-triiodo-L-thyronine (T3) in tissues from rats on a low iodine intake, despite normal circulating T3 levels.  Acta Endocrinol (Copenh). 1989;  120 490-498
    PubMedGoogle Scholar
  • 27 Serrano-Lozano A, Morata P, Montiel M, Perez-Aguilar J P, Morell M. L-thyroxine and L-triiodothyronine in the cerebral tissues of the adult rat. Effect of hypothyroidism.  Rev Esp Fisiol. 1991;  47 141-145
    PubMedGoogle Scholar
  • 28 Baumgartner A, Hiedra L, Pinna G, Eravci M, Prengel H, Meinhold H. Rat brain type II 5’-iodothyronine deiodinase activity is extremely sensitive to stress.  J Neurochem. 1998;  71 817-826
    PubMedGoogle Scholar
  • 29 Guadano-Ferraz A, Escamez M J, Rausell E, Bernal J. Expression of type 2 iodothyronine deiodinase in hypothyroid rat brain indicates an important role of thyroid hormone in the development of specific primary sensory systems.  J Neurosci. 1999;  19 3430-3439
    PubMedGoogle Scholar
  • 30 Leonard J L, Silva J E, Kaplan M M, Mellen S A, Visser T J, Larsen P R. Acute post-transcriptional regulation of cerebrocortical and pituitary iodothyronine 5’-deiodinases by thyroid hormone.  Endocrinology. 1984;  114 998-1004
    PubMedGoogle Scholar
  • 31 Meyer E M, Cooper J R. Correlations between Na+-K+ ATPase activity and acetylcholine release in rat cortical synaptosomes.  J Neurochem. 1981;  36 467-475
    PubMedGoogle Scholar
  • 32 Stahl W L, Harris W E. Na+, K+-ATPase: structure, function, and interactions with drugs.  Adv Neurol. 1986;  44 681-693
    PubMedGoogle Scholar
  • 33 Kastrup J, Christensen N J. Lack of effects of thyroid hormones on muscarine cholinergic receptors in rat brain and heart.  Scand J Clin Lab Invest. 1984;  44 33-38
    PubMedGoogle Scholar

P. K. Sarkar

Department of Biology
Rutgers University

315 Penn Street, Camden
New Jersey 08102
USA


Phone: Phone:+ 1 (856) 225-6165

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Email: E-mail:pksarkar@crab.rutgers.edu

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