<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article         dtd-version="1.4">
            <front>

                <journal-meta>
                                                                <journal-id>genel tıp derg</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Genel Tıp Dergisi</journal-title>
            </journal-title-group>
                                        <issn pub-type="epub">2602-3741</issn>
                                                                                            <publisher>
                    <publisher-name>Selcuk University</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id/>
                                                                                                                                                                                            <title-group>
                                                                                                                        <article-title>Dentat Girus İçerisine İnfüze Edilen T4&#039;ün Uzun Dönemli Etkinleşme Yanıtları Üzerine Etkisi ve Mitojen İle Aktive Olan Protein Kinazın Rolü</article-title>
                                                                                                                                                                                                <trans-title-group xml:lang="en">
                                    <trans-title>Dentate gyrus T4 infused into activation response effect of long-term, and  mitogen-activated protein kinase role</trans-title>
                                </trans-title-group>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                <name>
                                    <surname>Tan</surname>
                                    <given-names>Burak</given-names>
                                </name>
                                                                    <aff>Erciyes Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Kayseri</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Babur</surname>
                                    <given-names>Ercan</given-names>
                                </name>
                                                                    <aff>Erciyes Üniversitesi, Sağlık Bilimleri Enstitüsü, Kayseri</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Güler</surname>
                                    <given-names>Arzu Dilek</given-names>
                                </name>
                                                                    <aff>Erciyes Üniversitesi, Sağlık Bilimleri Enstitüsü, Kayseri</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Süer</surname>
                                    <given-names>Cem</given-names>
                                </name>
                                                                    <aff>Erciyes Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Kayseri</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Dursun</surname>
                                    <given-names>Nurcan</given-names>
                                </name>
                                                                    <aff>Erciyes Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Kayseri</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20200301">
                    <day>03</day>
                    <month>01</month>
                    <year>2020</year>
                </pub-date>
                                        <volume>30</volume>
                                        <issue>1</issue>
                                        <fpage>16</fpage>
                                        <lpage>23</lpage>
                        
                        <history>
                                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 1990, Genel Tıp Dergisi</copyright-statement>
                    <copyright-year>1990</copyright-year>
                    <copyright-holder>Genel Tıp Dergisi</copyright-holder>
                </permissions>
            
                                                                                                <abstract><p>Amaç: Bu çalışmada tiroksin hormonunun uzun dönemli güçlenme  UDG  yanıtları, N-metil-D aspartat  NMDA  reseptörü ve P38-Mitojenle Aktive Olan Protein Kinaz  P38 MAPK  üzerine olan etkisinin araştırılması amaçlanmıştır.Gereç ve Yöntem: Çalışma, 2-4 aylık erkek ve dişi Wistar albino sıçanlar üzerinde yapıldı. Sıçanlar üretan anestezisi altında stereotaksik çatıya yerleştirildi. Alan potansiyelleri perforan yolun uyarılmasına yanıt olarak dentat girustan kaydedildi. Bazal alan potansiyellerini takiben 15 dk süre ile hipokampüse tiroksin infüzyonu yapıldı. İnfüzyonu takiben 100 Hz frekanslı uyarım 5 dakika ara ile 4 kez uygulandı. Son tetanik uyarımdan 60 dakika sonra sıçanların hipokampüsleri çıkarıldı. Hipokampüs örneklerinden NR1, NR2A, NR2B ve P38 MAPK&#039;a ait gen anlatımlarının incelenmesi gerçek zamanlı kantitatif polimeraz zincir reaksiyonu  RT-qPCR  yöntemi ile yapıldı.Bulgular: Yüksek frekanslı uyarım verilmesi esnasında tetiklenen populasyon spike  PS  genliği ve eksitatör post sinaptik potansiyel  EPSP  eğiminin, tiroksinin hipokampüse infüze edilmesiyle her iki cinsiyette kontrole göre azaldığı belirlendi. Bununla uyumlu olarak, NR2B ve P38 MAPK düzeyleri için her iki cinsiyette kontrole göre artış olduğu belirlendi.Sonuç: Çalışma bulguları, tiroksin infüzyonunun sinaptik plastisiteyi inhibe ettiği ve bu inhibisyona NR2B ve P38 MAPK ekspresyonundaki değişimlerin aracılık ettiğine dair kanıtlar sunmaktadır</p></abstract>
                                                                                                                                    <trans-abstract xml:lang="en">
                            <p>Objective: In the present study, it was aimed to investigate the effect of the L-thyroxine hormone on long-term potentiation  LTP  responses, N-methyl-D aspartate  NMDA  receptor and P38-mitogen-activated protein kinase  P38 MAPK .Material and Method: The study was performed on 2-4 month old male and female Wistar albino rats. Rats were placed onto stereotaxic roof under anesthesia. Field potentials were recorded in dentate gyrus in response to perforant pathway stimulation. Hippocampal thyroxine infusion was performed for 15 min following basal field potentials. Following infusion, 100 Hz frequency stimulation was applied 4 times with 5 min intervals. After 60 minutes from the last tetanic stimulation, the hippocampus of the rats was removed. Examination of gene expression of NR1, NR2A, NR2B and P38 MAPK from hippocampal samples was performed by real-time quantitative polymerase chain reaction  RT-qPCR  method.Results: It has been determined that the population spike  PS  amplitude and the excitatory post synaptic potential  EPSP  triggered during high frequency stimulation are reduced in both sexes by hippocampal infusion of thyroxine.Conclusion: The findings of the study provide evidence that the infusion of thyroxine inhibits synaptic plasticity and that this inhibition is mediated by changes in NR2B and P38 MAPK expression</p></trans-abstract>
                                                            
            
                                                            <kwd-group>
                                                    <kwd>Tiroksin</kwd>
                                                    <kwd>   uzun dönemli güçlenme</kwd>
                                                    <kwd>   hipokampüs</kwd>
                                            </kwd-group>
                                                        
                                                                            <kwd-group xml:lang="en">
                                                    <kwd>Thyroxine</kwd>
                                                    <kwd>   long term potentiation</kwd>
                                                    <kwd>   hippocampus</kwd>
                                            </kwd-group>
                                                                                                            </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">Herron CE, Lester RA, Coan EJ, et al. Frequency-depen- dent involvement of NMDA receptors in the hippocampus: a novel synaptic mechanism. Nature 1986; 322: 265-8.</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">Blitzer RD, Connor JH, Brown GP, et al. Gating of CaM- KII by cAMP-regulated protein phosphatase activity during LTP. Science 1998; 280: 1940-3.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">Castro-Alamancos MA, Calcagnotto ME. Presynaptic long- term potentiation in corticothalamic synapses. J Neuros- cience 1999; 19: 9090-7.</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">Andersen P, Bliss TV, Skrede KK. Lamellar organization of hippocampal pathways. Exp Brain Res 1971; 13: 222-38.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">McNaughton B. Evidence for two physiologically distinct perforant pathways to the fascia dentata. Brain Res 1980; 199: 1-19.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">Bramham CR, Milgram NW, Srebro B. Activation of AP5‐ sensitive NMDA receptors is not required to induce LTP of synaptic transmission in the lateral perforant path. Eur J Neurosci 1991; 3: 1300-8.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">Colino A, Malenka RC. Mechanisms underlying induction of long-term potentiation in rat medial and lateral perfo- rant paths in vitro. J Neurophysiol 1993; 69: 1150-9.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">Bliss TV, Lİmo T. Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 1973; 232: 331-56.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">Rygh LJ, Tjİlsen A, Hole K, et al. Cellular memory in spinal nociceptive circuitry. Scandinavian journal of psychology 2002; 43: 153-9.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">Jones M, Errington M, French P, et al. A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nature neuroscience 2001; 4: 289-96.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">Plátenıik J, Kuramoto N, Yoneda Y. Molecular mechanisms associated with long-term consolidation of the NMDA sig- nals. Life sciences 2000; 67: 335-64.</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">Soderling TR, Derkach VA. Postsynaptic protein phosphorylation and LTP. Trends in neurosciences 2000; 23: 75-80.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">Arnsten AFT, Ramos BP, Birnbaum SG, et al. Protein kinase A as a therapeutic target for memory disorders: rationale and challenges. Trends in molecular medicine 2005; 11: 121-8.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">Songur A, Özen OA, Sarsılmaz M. Hipokampus. Turkiye Klinikleri Tıp Bilimleri Dergisi 2001; 21: 427-31.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">Pavlides C, Westlind-Danielsson A, Nyborg H, et al. Neo- natal hyperthyroidism disrupts hippocampal LTP and spa- tial learning. Experimental brain research 1991; 85: 559-64.</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">Colicos MA, Dash PK. Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits. Brain research 1996; 739: 120-31.</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">Fernández‐Lamo I, Montero‐Pedrazuela A, Delgado‐Gar- cía JM, et al. Effects of thyroid hormone replacement on associative learning and hippocampal synaptic plasticity in adult hypothyroid rats. European Journal of Neuroscience 2009; 30: 679-92.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">Gilbert M, Paczkowski C. Propylthiouracil (PTU)-indu- ced hypothyroidism in the developing rat impairs synaptic transmission and plasticity in the dentate gyrus of the adult hippocampus. Developmental Brain Research 2003; 145: 19-29.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">Gilbert M, Sui L. Dose-dependent reductions in spatial le- arning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficien- cy. Brain research 2006; 1069: 10-22.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">Lee PR, Brady D, Koenig JI. Thyroid hormone regulation of N‐methyl‐D‐aspartic acid receptor subunit mRNA expres- sion in adult brain. Journal of neuroendocrinology 2003; 15: 87-92.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">MacDonald JF, Jackson MF, Beazely MA. G protein-coup- led receptors control NMDARs and metaplasticity in the hippocampus. Biochimica et Biophysica Acta (BBA)-Bio- membranes 2007; 1768: 941-51.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">Barbakadze T, Natsvlishvili N, Mikeladze D. Thyroid hor- mones differentially regulate phosphorylation of ERK and Akt via integrin αvβ3 receptor in undifferentiated and diffe- rentiated PC‐12 cells. Cell biochemistry and function 2014; 32: 282-6.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">Yonkers MA, Ribera AB. Molecular components underl- ying nongenomic thyroid hormone signaling in embryonic zebrafish neurons. Neural development 2009 ;4: 20-32.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">Hermann P, Armant M, Brown E, et al. The vitronectin receptor and its associated CD47 molecule mediates pro- inflammatory cytokine synthesis in human monocytes by interaction with soluble CD23. The Journal of cell biology 1999; 144: 767-75.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">Wu X, Reddy DS. Integrins as receptor targets for neuro- logical disorders. Pharmacology &amp; therapeutics 2012; 134: 68-81.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">Davis PJ, Davis FB. Nongenomic actions of thyroid hormo- ne. Thyroid 1996; 6: 497-504.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">Giese KP, Mizuno K. The roles of protein kinases in lear- ning and memory. Learning &amp; memory 2013; 20: 540-52.</mixed-citation>
                    </ref>
                                    <ref id="ref28">
                        <label>28</label>
                        <mixed-citation publication-type="journal">Brown TC, Tran IC, Backos DS, et al. NMDA receptor-de- pendent activation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD. Neuron 2005; 45: 81-94.</mixed-citation>
                    </ref>
                                    <ref id="ref29">
                        <label>29</label>
                        <mixed-citation publication-type="journal">Gisabella B, Rowan MJ, Anwyl R. Mechanisms underlying the inhibition of long-term potentiation by preconditio- ning stimulation in the hippocampus in vitro. Neuroscience 2003; 121: 297-305.</mixed-citation>
                    </ref>
                                    <ref id="ref30">
                        <label>30</label>
                        <mixed-citation publication-type="journal">Huang YY, Pittenger C, Kandel ER. A form of long-lasting, learning-related synaptic plasticity in the hippocampus in- duced by heterosynaptic low-frequency pairing. Proceedin- gs of the National Academy of Sciences 2004; 101: 859-64.</mixed-citation>
                    </ref>
                                    <ref id="ref31">
                        <label>31</label>
                        <mixed-citation publication-type="journal">Krapivinsky G, Medina I, Krapivinsky L, et al. Syn- GAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent sy- naptic AMPA receptor potentiation. Neuron 2004; 43: 563- 74.</mixed-citation>
                    </ref>
                                    <ref id="ref32">
                        <label>32</label>
                        <mixed-citation publication-type="journal">Li S, Tian X, Hartley DM, et al. Distinct roles for Ras-guani- ne nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression. Journal of Neuroscience 2006; 26: 1721-9.</mixed-citation>
                    </ref>
                                    <ref id="ref33">
                        <label>33</label>
                        <mixed-citation publication-type="journal">Zhu JJ, Qin Y, Zhao M, et al. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 2002; 110: 443-55.</mixed-citation>
                    </ref>
                                    <ref id="ref34">
                        <label>34</label>
                        <mixed-citation publication-type="journal">Smith JW, Evans AT, Costall B, et al. Thyroid hormones, brain function and cognition: a brief review. Neuroscience &amp; Biobehavioral Reviews 2002; 26: 45-60.</mixed-citation>
                    </ref>
                                    <ref id="ref35">
                        <label>35</label>
                        <mixed-citation publication-type="journal">Hökfelt T, Tsuruo Y, Ulfhake B, et al. SECTION II. SYNAP- TIC ROLE OF TRH: Distribution of TRH‐like Immunore- activity with Special Reference to Coexistence with Other Neuroactive Compounds a. Annals of the New York Aca- demy of Sciences 1989; 553: 76-105.</mixed-citation>
                    </ref>
                                    <ref id="ref36">
                        <label>36</label>
                        <mixed-citation publication-type="journal">Ishihara K, Katsuki H, Kawabata A, et al. Effects of thyrot- ropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices. Brain research 1991; 554: 203-8.</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
