Tiroit Hormonlarının Yüksek Frekanslı Uyarım ile Tetiklenen Sinaptik Gücün Depotansiyasyonu Üzerine Etkisi

Yıl 2021, Cilt: 31 Sayı: 4, 369 - 374, 15.12.2021

Burak Tan Ercan Babur , Cem Süer Nurcan Dursun

https://doi.org/10.54005/geneltip.1036595

Öz

Önceki çalışma bulgularımız, normal tiroit hormon düzeylerinin sinaptik plastisitenin göstergeleri olan uzun dönemli güçlenme (UDG) ve uzun dönemli baskılanma (UDB) yanıtları arasındaki dengenin oluşmasında rol oynayabileceğini göstermektedir. Sinaptik plastisitenin bir diğer formu olan depotansiyasyon (DP) ise şu ana kadar bu bağlamda çalışılmamıştır. Bu çalışmada, tiroid hormonları ile sinaptik plastisite arasındaki ilişkiyi anlamak için, hipokampüse infüze edilen T4 ve T3 hormonlarının DP büyüklüğünü değiştirip değiştirmediği araştırılmıştır.

Deneyler, yüksek frekanslı uyarım (YFU) sırasında SF, T4 ve T3 infüze edilen ve düşük frekanslı uyarım (DFU) sırasında SF, T4 ve T3 infüze edilen 2 aylık Wistar albino erkek sıçanlardan oluşan (n=7/grup) 3 grup olarak gerçekleştirildi. Depotansiyasyonu indüklemek için, YFU kalıbı olarak 1 sn süreli 100 Hz frekanslı 4 tekrarlı uyarımı takiben 5 dk sonra, DFU kalıbı olarak 1 Hz frekanslı 900 pulse uyarım kullanıldı. Böylece uyarılan nöron havuzundaki sinapslarda hem yeni sinaps oluşumu hem de silinmesi elektriksel olarak tetiklendi ve kayıtlandı.

T4 hormonunun YFU sırasında uygulanmasının popülasyon spike (PS) genliğini kontrol grubuna göre değiştirdiği (p<0,001), DFU sırasında uygulanmasının ise etkilemediği (p>0,05) bulundu. T4 hormonunun YFU veya DFU sırasında uygulanmasının eksitatör postsinaptik potansiyel (EPSP) eğimindeki zamansal değişimlerinin ve T3 hormonunun YFU veya DFU sırasında uygulanmasının PS genliği ve EPSP eğimindeki zamansal değişimlerinin SF infüzyonu yapılanlar ile aynı olduğu bulundu.

Bu sonuçlar, T4’ün YFU sırasında uygulanmasının DP yanıtı üzerinde anlamlı bir etkiye sahip olduğunu, DFU sırasında T4 uygulanmasının ise, DP yanıtı üzerinde anlamlı bir etkiye sahip olmadığını düşündürmektedir.

Anahtar Kelimeler

Sinaptik plastisite, Depotansiyasyon, Tiroit hormonları, Hipokampüs

The Effect of Thyroid Hormones on Depotentiation of Synaptic Strengthening Which is Induced by High Frequency Stimulation

Öz

Our previous study findings showed that normal thyroid hormone levels may play a role in the balance between long-term potentiation (LTP) and long-term depression (LTD) that are indicative of synaptic plasticity. Depotentiation (DP), another form of synaptic plasticity, has not been studied in this context so far. In the present study, we aimed to learn the effect of infused T4 hormone on the depotentiation magnitude and the relationship between T4 and synaptic plasticity.

Experiments were performed in 3 groups of 2-month-old Wistar albino male rats (n=7/group) infused with SF, T4 and T3 during high frequency stimulation (HFS) or during low frequency stimulation (LFS). Depotentiation was induced by a HFS (100Hz,1 sec, 4 times), followed by LFS (900-pulse stimulation at 1 Hz). Thus, both synapse formation and deletion were electrically triggered and recorded in synapses of the stimulated neuron pool.

It was found that infusion of T4 during HFS decreased the PS amplitude compared to that control group (p <0.001), but infusion during LFS did not affect it (p> 0.05). It was found that the temporal changes in the EPSP slope of the infusion of T4 during HFS or LFS and the temporal changes in the PS amplitude and EPSP slope of the infusion of T3 during HFS or LFS were the same as the SF infusion.

These results suggested that the application of T4 during HFS have a significant effect on DP but the application of T4 during LFS does not seem to have a significant effect on DP.

Anahtar Kelimeler

Synaptic plasticity, Depotentiation, Thyroid hormones, Hippocampus

Kaynakça

• Bliss TV, Lømo T. Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. The Journal of physiology 1973;232:331-56
• Dudek SM, Bear MF. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. In: ed. editor^editors., World Scientific, 1995 Date: p. 200-4.
• Barrionuevo G, Schottler F, Lynch G. The effects of repetitive low frequency stimulation on control and “potentiated” synaptic responses in the hippocampus. Life sciences 1980;27:2385-91
• D Skaper S, Facci L, Zusso M, et al. Synaptic plasticity, dementia and Alzheimer disease. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders) 2017;16:220-33
• Wang F, Geng X, Tao H-Y, et al. The restoration after repetitive transcranial magnetic stimulation treatment on cognitive ability of vascular dementia rats and its impacts on synaptic plasticity in hippocampal CA1 area. Journal of molecular neuroscience 2010;41:145-55
• Martí-Carbonell MA, Garau A, Sala-Roca J, et al. Effects of adult dysthyroidism on the morphology of hippocampal granular cells in rats. Acta Neurobiol Exp 2012;72:230-9
• Sala-Roca J, Estebanez-Perpina E, Balada F, et al. Effects of adult dysthyroidism on the morphology of hippocampal neurons. Behavioural brain research 2008;188:348-54
• Taşkın E, Artis AS, Bitiktas S, et al. Experimentally induced hyperthyroidism disrupts hippocampal long-term potentiation in adult rats. Neuroendocrinology 2011;94:218-27
• Pavlides C, Westlind-Danielsson A, Nyborg H, et al. Neonatal hyperthyroidism disrupts hippocampal LTP and spatial learning. Experimental brain research 1991;85:559-64
• Alzoubi K, Aleisa A, Alkadhi K. Adult-onset hypothyroidism facilitates and enhances LTD: reversal by chronic nicotine treatment. Neurobiology of disease 2007;26:264-72
• Tan B, Bitiktaş S, Kavraal Ş, et al. Low-frequency stimulation induces a durable long-term depression in young adult hyperthyroid rats: the role of p38 mitogen-activated protein kinase and protein phosphatase 1. Neuroreport 2016;27:640-6
• Bitiktaş S, Tan B, Kavraal Ş, et al. The effects of intra‐hippocampal L‐thyroxine infusion on long‐term potentiation and long‐term depression: A possible role for the αvβ3 integrin receptor. Journal of neuroscience research 2017;95:1621-32
• Chaudhury D, Wang LM, Colwell CS. Circadian regulation of hippocampal long-term potentiation. Journal of biological rhythms 2005;20:225-36
• Caria MA, Dratman MB, Kow LM, et al. Thyroid hormone action: nongenomic modulation of neuronal excitability in the hippocampus. Journal of neuroendocrinology 2009;21:98-107
• Bradley DJ, Young WS, Weinberger C. Differential expression of alpha and beta thyroid hormone receptor genes in rat brain and pituitary. Proceedings of the National Academy of Sciences 1989;86:7250-4
• Gilbert M, Sui L. Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency. Brain research 2006;1069:10-22
• Artis A, Bitiktas S, Taşkın E, et al. Experimental hypothyroidism delays field excitatory post‐synaptic potentials and disrupts hippocampal long‐term potentiation in the dentate gyrus of hippocampal formation and Y‐maze performance in adult rats. Journal of neuroendocrinology 2012;24:422-33
• Dutar P, Bassant M-H, Senut M-C, et al. The septohippocampal pathway: structure and function of a central cholinergic system. Physiological reviews 1995;75:393-427
• Gould E, Allan MD, McEwen BS. Dendritic spine density of adult hippocampal pyramidal cells is sensitive to thyroid hormone. Brain research 1990;525:327-9
• Cook CB, Kakucska I, Lechan RM, et al. Expression of thyroid hormone receptor beta 2 in rat hypothalamus. Endocrinology 1992;130:1077-9
• Bassett J, Harvey CB, Williams GR. Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions. Molecular and cellular endocrinology 2003;213:1-11
• Davis PJ, Davis FB. Nongenomic actions of thyroid hormone. In: ed. editor^editors., Springer, 2003 Date: p. 19-37.
• Davis PJ, Davis FB. Nongenomic actions of thyroid hormone on the heart. Thyroid 2002;12:459-66
• Davis PJ, Davis FB, Cody V. Membrane receptors mediating thyroid hormone action. Trends in Endocrinology & Metabolism 2005;16:429-35
• Shi YB, Wong J, Puzianowska‐Kuznicka M, et al. Tadpole competence and tissue‐specific temporal regulation of amphibian metamorphosis: Roles of thyroid hormone and its receptors. Bioessays 1996;18:391-9
• Kavok NS, Krasilnikova OA, Babenko NA. Thyroxine signal transduction in liver cells involves phospholipase C and phospholipase D activation. Genomic independent action of thyroid hormone. BMC cell biology 2001;2:5
• Davis PJ, Davis FB, Lawrence WD. Thyroid hormone regulation of membrane Ca2+-ATPase activity. Endocrine research 1989;15:651-82
• Lakatos P, Stern PH. Evidence for direct non-genomic effects of triiodothyronine on bone rudiments in rats: stimulation of the inositol phosphate second messenger system. Acta endocrinologica 1991;125:603-8
• Lin H-Y, Yen PM, Davis FB, et al. Protein synthesis-dependent potentiation by thyroxine of antiviral activity of interferon-γ. American Journal of Physiology-Cell Physiology 1997;273:C1225-C32
• Lin H-Y, Davis FB, Gordinier JK, et al. Thyroid hormone induces activation of mitogen-activated protein kinase in cultured cells. American Journal of Physiology-Cell Physiology 1999;276:C1014-C24
• Storey NM, O'Bryan JP, Armstrong DL. Rac and Rho mediate opposing hormonal regulation of the ether-a-go-go-related potassium channel. Current Biology 2002;12:27-33
• Davis PJ, Shih A, Lin H-Y, et al. Thyroxine promotes association of mitogen-activated protein kinase and nuclear thyroid hormone receptor (TR) and causes serine phosphorylation of TR. Journal of Biological Chemistry 2000;275:38032-9
• Shih A, Lin H-Y, Davis FB, et al. Thyroid hormone promotes serine phosphorylation of p53 by mitogen-activated protein kinase. Biochemistry 2001;40:2870-8
• Jones K, Brubaker J, Chin W. Evidence that phosphorylation events participate in thyroid hormone action. Endocrinology 1994;134:543-8
• Leitman DC, Costa CH, Graf H, et al. Thyroid hormone activation of transcription is potentiated by activators of cAMP-dependent protein kinase. Journal of Biological Chemistry 1996;271:21950-5
• Ting Y-T, Bhat MK, Wong R, et al. Tissue-specific stabilization of the thyroid hormone β1 nuclear receptor by phosphorylation. Journal of Biological Chemistry 1997;272:4129-34
• Katz D, Reginato MJ, Lazar MA. Functional regulation of thyroid hormone receptor variant TR alpha 2 by phosphorylation. Molecular and cellular biology 1995;15:2341-8