{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:43:49Z","timestamp":1790649829390,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Thyroid hormones (THs) are essential in normal brain development, and cognitive and emotional functions. THs act through a cascade of events including uptake by the target cells by specific cell membrane transporters, activation or inactivation by deiodinase enzymes, and interaction with nuclear thyroid hormone receptors. Several thyroid responsive genes have been described in the developing and in the adult brain and many studies have demonstrated a systemic or local reduction in TH availability in neurologic disease and after brain injury. In this review, the main factors and mechanisms associated with the THs in the normal and damaged brain will be evaluated in different regions and cellular contexts. Furthermore, the most common animal models used to study the role of THs in brain damage and cognitive impairment will be described and the use of THs as a potential recovery strategy from neuropathological conditions will be evaluated. Finally, particular attention will be given to the link observed between TH alterations and increased risk of Alzheimer\u2019s Disease (AD), the most prevalent neurodegenerative and dementing condition worldwide.<\/jats:p>","DOI":"10.3390\/biom14020198","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T03:47:09Z","timestamp":1707277629000},"page":"198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Factors and Mechanisms of Thyroid Hormone Activity in the Brain: Possible Role in Recovery and Protection"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-5042","authenticated-orcid":false,"given":"Laura","family":"Sabatino","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, National Council of Research, Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominga","family":"Lapi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Del Seppia","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, National Council of Research, Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"ref_1","first-page":"94","article-title":"The role of thyroid hormones in prenatal and neonatal neurological development\u2014Current perspectives","volume":"14","author":"Porterfield","year":"1993","journal-title":"Endocr. Rev."},{"key":"ref_2","first-page":"462","article-title":"Molecular basis of thyroid hormone-dependent brain development","volume":"18","author":"Oppenheimer","year":"1997","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.beem.2004.03.012","article-title":"Maternal thyroid hormones early in pregnancy and fetal brain development","volume":"18","author":"Obregon","year":"2004","journal-title":"Best Pract. Res. Clin. Endocrinol. Metabol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/01.med.0000151393.51033.fa","article-title":"The role of thyroid hormone in fetal and neonatal brain development","volume":"12","author":"Jones","year":"2005","journal-title":"Curr. Opin. Endocrinol. Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1210\/edrv.23.1.0455","article-title":"Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases","volume":"23","author":"Bianco","year":"2002","journal-title":"Endocr. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fendo.2014.00098","article-title":"Transport of thyroid hormone in brain","volume":"5","author":"Wirth","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.beem.2007.04.001","article-title":"Thyroid hormone transporters in health and disease: Advances in thyroid hormone deiodination","volume":"21","year":"2007","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tedeschi, L., Vassalle, C., Iervasi, G., and Sabatino, L. (2021). Main Factors Involved in Thyroid Hormone Action. Molecules, 26.","DOI":"10.3390\/molecules26237337"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3803\/EnM.2021.1198","article-title":"Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions","volume":"36","author":"Sabatino","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1210\/er.2008-0019","article-title":"Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling","volume":"29","author":"Gereben","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1210\/er.2009-0007","article-title":"Molecular aspects of thyroid hormone actions","volume":"31","author":"Cheng","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrendo.2015.205","article-title":"Nongenomic actions of thyroid hormone","volume":"12","author":"Davis","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.yfrne.2007.09.003","article-title":"Mechanisms of nongenomic actions of thyroid hormone","volume":"29","author":"Davis","year":"2008","journal-title":"Front. Neuroendocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1210\/en.2005-1390","article-title":"Proangiogenesis action of the thyroid hormone analog 3,5-diiodothyropropionic acid (ditpa) is initiated at the cell surface and is integrin mediated","volume":"147","author":"Mousa","year":"2006","journal-title":"Endocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1089\/105072503770867219","article-title":"Control of thyroid hormone action in the developing rat brain","volume":"13","author":"Anderson","year":"2003","journal-title":"Thyroid"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0083-6729(05)71004-9","article-title":"Thyroid hormones and brain development","volume":"71","author":"Bernal","year":"2005","journal-title":"Vitam. Horm."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alcaide, M.A., and Mayerl, S. (2023). Local thyroid hormone action in brain development. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512352"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00920","DOI":"10.1002\/brb3.920","article-title":"Maternal hormonal milieu influence on fetal brain development","volume":"8","author":"Miranda","year":"2018","journal-title":"Brain Behav."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1111\/1471-0528.12681","article-title":"Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: A Danish nationwide cohort study","volume":"121","author":"Andersen","year":"2014","journal-title":"BJOG"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/cen.12415","article-title":"Psychiatric disease in late adolescence and young adulthood. Foetal programming by maternal hypothyroidism?","volume":"81","author":"Andersen","year":"2014","journal-title":"Clin. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.5698\/1535-7597-13.4.172","article-title":"Interneuron development and epilepsy: Early genetic defects cause long-term consequences in seizures and susceptibility","volume":"13","author":"Powell","year":"2013","journal-title":"Epilepsy Curr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1016\/j.bbagen.2012.06.003","article-title":"Thyroid hormone receptors: The challenge of elucidating isotype-specific functions and cell-specific response","volume":"1830","author":"Flamant","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1210\/me.2010-0175","article-title":"The thyroid hormone receptor {alpha}1 protein is expressed in embryonic postmitotic neurons and persists in most adult neurons","volume":"24","author":"Wallis","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_24","first-page":"184","article-title":"Thyroid hormone receptors: Multiple forms, multiple possibilities","volume":"14","author":"Lazar","year":"1993","journal-title":"Endocr. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1002\/cphy.c200019","article-title":"The Role of Thyroid Hormone in Neuronal Protection","volume":"11","author":"Liu","year":"2021","journal-title":"Compr. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1016\/j.bbagen.2012.04.014","article-title":"Thyroid hormone receptor activity in the absence of ligand: Physiological and developmental implications","volume":"1830","author":"Bernal","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1083\/jcb.121.2.423","article-title":"Thyroid hormone receptor\/c-erbA: Control of commitment and differentiation in the neuronal\/chromaffin progenitor line PC12","volume":"121","author":"Wrighton","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nrendo.2015.66","article-title":"Thyroid hormone transport\u2014Functions and clinical implications","volume":"11","author":"Bernal","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/bs.vh.2017.04.005","article-title":"Thyroid Hormone Transport and Transporters","volume":"Volume 106","author":"Litwack","year":"2018","journal-title":"Vitamins and Hormones"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1756-6614-4-S1-S7","article-title":"Primary and secondary thyroid hormone transporters","volume":"4","author":"Kinne","year":"2011","journal-title":"Thyroid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40128","DOI":"10.1074\/jbc.M300909200","article-title":"Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter","volume":"278","author":"Friesema","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1210\/me.2005-0256","article-title":"Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism","volume":"20","author":"Friesema","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/S0140-6736(04)17226-7","article-title":"Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation","volume":"364","author":"Friesema","year":"2004","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1086\/380999","article-title":"A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene","volume":"74","author":"Dumitrescu","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.beem.2007.03.009","article-title":"The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome","volume":"21","author":"Schwartz","year":"2007","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6251","DOI":"10.1210\/en.2008-0378","article-title":"Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier","volume":"149","author":"Roberts","year":"2008","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9439","DOI":"10.1523\/JNEUROSCI.6055-08.2009","article-title":"Neuronal 3\u2019,3,5- triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome","volume":"29","author":"Wirth","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1210\/me.2007-0112","article-title":"Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10","volume":"22","author":"Friesema","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"bnz008","DOI":"10.1210\/endrev\/bnz008","article-title":"Thyroid Hormone Transporters","volume":"41","author":"Groeneweg","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1111\/j.1476-5381.2011.01724.x","article-title":"OATPs, OATs and OCTs: The organic anion and cation transporters of the SLCO and SLC22A gene superfamilies","volume":"165","author":"Roth","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1210\/en.2004-1179","article-title":"The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations","volume":"146","author":"Heuer","year":"2005","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.tem.2007.11.003","article-title":"Thyroid hormone transport in and out of cells","volume":"19","author":"Visser","year":"2008","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3940(01)01810-9","article-title":"Predominant functional activity of the large, neutral amino acid transporter LAT1 isoform at the cerebrovasculature","volume":"306","author":"Killian","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1210\/en.2009-0209","article-title":"A thyroid hormone analog with reduced dependence on the monocarboxylate transporter 8 for tissue transport","volume":"150","author":"Liao","year":"2009","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1210\/en.2015-1234","article-title":"The Thyroid Hormone Analog DITPA Ameliorates Metabolic Parameters of Male Mice with Mct8 Deficiency","volume":"156","author":"Ferrara","year":"2015","journal-title":"Endocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mce.2017.02.029","article-title":"Therapeutic applications of thyroid hormone analogues in resistance to thyroid hormone (RTH) syndromes","volume":"458","author":"Groeneweg","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1210\/me.2014-1135","article-title":"In Vitro and Mouse Studies Supporting Therapeutic Utility of Triiodothyroacetic Acid in MCT8 Deficiency","volume":"28","author":"Kersseboom","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"723750","DOI":"10.3389\/fendo.2021.723750","article-title":"Monocarboxylate Transporter 8 Deficiency: From Pathophysiological Understanding to Therapy Development","volume":"12","author":"Gunhanlar","year":"2021","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1172\/JCI70324","article-title":"Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis","volume":"124","author":"Mayerl","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1089\/thy.2020.0649","article-title":"Brain Gene Expression in Systemic Hypothyroidism and Mouse Models of MCT8 Deficiency: The Mct8-Oatp1c1-Dio2 Triad","volume":"31","author":"Morte","year":"2021","journal-title":"Thyroid"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S2213-8587(19)30155-X","article-title":"Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: An international, single-arm, open-label, phase 2 trial","volume":"7","author":"Groeneweg","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1136","DOI":"10.1210\/clinem\/dgab750","article-title":"Long-Term Efficacy of T3 Analogue Triac in Children and Adults with MCT8 Deficiency: A Real-Life Retrospective Cohort Study","volume":"107","author":"Groeneweg","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.freeradbiomed.2022.09.024","article-title":"Deiodinases control local cellular and systemic thyroid hormone availability","volume":"193","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1007\/s00018-007-7396-0","article-title":"Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences","volume":"65","author":"Gereben","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0024-3205(00)00929-2","article-title":"A study of iodothyronine 5\u2032-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues","volume":"68","author":"Sabatino","year":"2000","journal-title":"Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1089\/10507250152484565","article-title":"A radioimmunoassay for type I iodothyronine 5\u2032-monodeiodinase in human tissues","volume":"11","author":"Sabatino","year":"2001","journal-title":"Thyroid"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1172\/JCI25083","article-title":"Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans","volume":"115","author":"Maia","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1210\/en.2008-1572","article-title":"Life without thyroxine to 3,5,3\u0374- triiodothyronine conversion: Studies in mice devoid of the 5\u0374-deiodinases","volume":"150","author":"Galton","year":"2009","journal-title":"Endocrinology"},{"key":"ref_59","first-page":"E715","article-title":"Thyroidal and peripheral production of 3,5,3\u2032-triiodothyronine in humans by multicompartmental analysis","volume":"258","author":"Pilo","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_60","first-page":"51","article-title":"A comparison of the effects of propylthiouracil and methimazol on circulating thyroid hormones and various measures of peripheral thyroid hormone effects in thyrotoxic patients","volume":"108","author":"Laurberg","year":"1985","journal-title":"Acta Endocrinol. (Copenh)"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1210\/mend.14.11.0558","article-title":"Selective proteolysis of human type 2 deiodinase: A novel ubiquitin-proteasomal mediated mechanism for regulation of hormone activation","volume":"14","author":"Gereben","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1210\/en.2008-1643","article-title":"Tanycyte pyroglutamyl peptidase II contributes to regulation of the hypothalamic-pituitary-thyroid axis through glial-axonal associations in the median eminence","volume":"150","author":"Vargas","year":"2009","journal-title":"Endocrinology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1172\/JCI41977","article-title":"Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells","volume":"120","author":"Freitas","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1210\/en.2016-1272","article-title":"Type 2 Deiodinase Disruption in Astrocytes Results in Anxiety-Depressive-Like Behavior in Male Mice","volume":"157","author":"Bocco","year":"2016","journal-title":"Endocrinology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1172\/JCI61231","article-title":"Coordination of hypothalamic and pituitary T3 production regulates TSH expression","volume":"123","author":"Fonseca","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"10391","DOI":"10.1073\/pnas.94.19.10391","article-title":"The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain","volume":"94","author":"Obregon","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3389\/fendo.2019.00401","article-title":"Tanycytes and the Control of Thyrotropin-Releasing Hormone Flux into Portal Capillaries","volume":"10","author":"Lazcano","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10526","DOI":"10.1073\/pnas.1323873111","article-title":"Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism","volume":"111","author":"Schweizer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1530\/JOE-11-0002","article-title":"Deiodinases: The balance of thyroid hormone: Local impact of thyroid hormone inactivation","volume":"209","author":"Dentice","year":"2011","journal-title":"J. Endocrinol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S2213-8587(15)00225-9","article-title":"Thyroid function in critically ill patients","volume":"3","author":"Fliers","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0002-9440(10)65309-6","article-title":"Genomic imprinting: Implications for human disease","volume":"154","author":"Falls","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1086\/302233","article-title":"Imprinting-mutation mechanisms in Prader-Willi syndrome","volume":"64","author":"Ohta","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1172\/JCI9340","article-title":"Beckwith-Wiedemann syndrome: Imprinting in clusters revisited","volume":"105","author":"Maher","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4483","DOI":"10.1210\/en.2002-220800","article-title":"The gene locus encoding iodothyronine deiodinase type 3 (Dio3) is imprinted in the fetus and expresses antisense transcripts","volume":"143","author":"Hernandez","year":"2002","journal-title":"Endocrinology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1210\/me.2014-1210","article-title":"Genomic imprinting variations in the mouse type 3 deiodinase gene between tissues and brain regions","volume":"28","author":"Martinez","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1523\/JNEUROSCI.12-06-02288.1992","article-title":"Spatial and temporal expression of alpha- and beta-thyroid hormone receptor mRNAs, including the beta 2-subtype, in the developing mammalian nervous system","volume":"12","author":"Bradley","year":"1992","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.phrs.2012.12.009","article-title":"Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury","volume":"70","author":"Crupi","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.mce.2017.05.023","article-title":"Thyroid hormone treatment activates protective pathways in both in vivo and in vitro models of neuronal injury","volume":"452","author":"Li","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/jcbfm.2009.216","article-title":"Stimulatory effects of thyroid hormone on brain angiogenesis in vivo and in vitro","volume":"30","author":"Zhang","year":"2010","journal-title":"J Cereb. Blood Flow Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1602\/neurorx.2.3.410","article-title":"Animal models of head trauma","volume":"2","author":"Cernak","year":"2005","journal-title":"NeuroRX"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s12311-009-0114-8","article-title":"Models of traumatic cerebellar injury","volume":"8","author":"Potts","year":"2009","journal-title":"Cerebellum"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"287","DOI":"10.31887\/DCNS.2011.13.2\/tmcallister","article-title":"Neurobiological consequences of traumatic brain injury","volume":"13","author":"McAllister","year":"2011","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/1097-4547(20010215)63:4<313::AID-JNR1025>3.0.CO;2-4","article-title":"Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury","volume":"63","author":"Dash","year":"2001","journal-title":"J. Neurosci. Res."},{"key":"ref_84","first-page":"65","article-title":"Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat","volume":"25","author":"Urrea","year":"2007","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jns.2015.04.042","article-title":"Anti-edema action of thyroid hormone in MCAO model of ischemic brain stroke: Possible association with AQP4 modulation","volume":"354","author":"Sadana","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev.neuro.20.1.245","article-title":"Bcl-2 gene family in the nervous system","volume":"20","author":"Merry","year":"1997","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1126\/science.281.5381.1312","article-title":"Caspases: Enemies within","volume":"281","author":"Thornberry","year":"1998","journal-title":"Science"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"468","DOI":"10.4103\/2230-8210.183476","article-title":"Prevalence of anxiety and depressive symptoms among patients with hypothyroidism","volume":"20","author":"Bathla","year":"2016","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1159\/000521650","article-title":"Thyroid Disorders and Development of Cognitive Impairment: A Review Study","volume":"112","author":"Talebi","year":"2022","journal-title":"Neuroendocrinology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1101\/gad.346105","article-title":"Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor alpha1 can be ameliorated by T3 treatment","volume":"19","author":"Venero","year":"2005","journal-title":"Genes Dev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1523\/JNEUROSCI.5163-07.2008","article-title":"Locomotor deficiencies and aberrant development of subtype-specific GABAergic interneurons caused by an unliganded thyroid hormone receptor alpha1","volume":"28","author":"Wallis","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1007\/s12035-018-1111-z","article-title":"Thyroid Hormone Supplementation Restores Spatial Memory, Hippocampal Markers of Neuroinflammation, Plasticity-Related Signaling Molecules, and \u03b2-Amyloid Peptide Load in Hypothyroid Rats","volume":"56","author":"Chaalal","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"112892","DOI":"10.1016\/j.physbeh.2020.112892","article-title":"Modulation of glutamate levels and Na+,K+-ATPase activity contributes to the chrysin memory recovery in hypothyroidism mice","volume":"222","author":"Bortolotto","year":"2020","journal-title":"Physiol. Behav."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0149-7634(01)00037-9","article-title":"Thyroid hormones, brain function and cognition: A brief review","volume":"26","author":"Smith","year":"2002","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/hipo.20476","article-title":"Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: Behavioral, electrophysiological, and molecular studies","volume":"19","author":"Alzoubi","year":"2009","journal-title":"Hippocampus"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.reprotox.2016.05.017","article-title":"Thyroid hormone disruption and cognitive impairment in rats exposed to PBDE during postnatal development","volume":"63","author":"Kuriyama","year":"2016","journal-title":"Reprod. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1210\/en.2015-1643","article-title":"Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats","volume":"157","author":"Gilbert","year":"2016","journal-title":"Endocrinology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.neuroscience.2016.04.048","article-title":"Effects of maternal hypothyroidism during pregnancy on learning, memory and hippocampal BDNF in rat pups: Beneficial effects of exercise","volume":"329","author":"Shafiee","year":"2016","journal-title":"Neuroscience"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ijdevneu.2013.01.003","article-title":"Treadmill exercise ameliorates symptoms of methimazole-induced hypothyroidism through enhancing neurogenesis and suppressing apoptosis in the hippocampus of rat pups","volume":"31","author":"Shin","year":"2013","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.physbeh.2007.03.008","article-title":"Age-related learning and memory impairments in adult-onset hypothyroidism in Kunming mice","volume":"91","author":"Tong","year":"2007","journal-title":"Physiol. Behav."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2008.05.020","article-title":"Developmental neurotoxicity of propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes","volume":"232","author":"Axelstad","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.physbeh.2016.06.016","article-title":"Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice","volume":"164","author":"Vasilopoulou","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bbr.2006.10.030","article-title":"Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha","volume":"177","author":"Wilcoxon","year":"2007","journal-title":"Behav. Brain. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Montero-Pedrazuela, A., Fern\u00e1ndez-Lamo, I., Alieva, M., Pereda-P\u00e9rez, I., Venero, C., and Guada\u00f1o-Ferraz, A. (2011). Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026582"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.yhbeh.2013.11.008","article-title":"Thyroid hormones regulate anxiety in the male mouse","volume":"65","author":"Buras","year":"2014","journal-title":"Horm. Behav."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/jdn.10243","article-title":"Methimazole-induced gestational hypothyroidism affects the offspring development and differently impairs the conditioned fear in male and female adulthood rodents","volume":"83","author":"Batista","year":"2023","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.bbr.2016.12.032","article-title":"Testing the correlation between experimentally-induced hypothyroidism during pregnancy and autistic-like symptoms in the rat offspring","volume":"321","author":"Melancia","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bbr.2019.03.027","article-title":"Effects of a rat model of gestational hypothyroidism on forebrain dopaminergic, GABAergic, and serotonergic systems and related behaviors","volume":"2","author":"Menezes","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnins.2018.00025","article-title":"Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer\u2019s Disease","volume":"12","author":"Kametani","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.brainresbull.2013.10.011","article-title":"Levothyroxin replacement therapy restores hypothyroidism induced impairment of L-LTP induction: Critical role of CREB","volume":"100","author":"Alzoubi","year":"2014","journal-title":"Brain Res. Bull."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000087648","article-title":"Thyroid hormones affect neurogenesis in the dentate gyrus of adult rat","volume":"81","author":"Ambrogini","year":"2005","journal-title":"Neuroendocrinology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/hipo.22319","article-title":"PTU-induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer\u2019s disease in the hippocampus and spatial memory impairments","volume":"24","author":"Chaalal","year":"2014","journal-title":"Hippocampus"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1089\/thy.2006.16.1207","article-title":"Thyroid hormone regulates endogenous amyloid-beta precursor protein gene expression and processing in both in vitro and in vivo models","volume":"16","author":"Oh","year":"2006","journal-title":"Thyroid"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"30366","DOI":"10.1074\/jbc.273.46.30366","article-title":"Thyroid hormone negatively regulates the transcriptional activity of the beta-amyloid precursor protein gene","volume":"273","author":"Belandia","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1210\/me.2003-0260","article-title":"A response unit in the first exon of the beta-amyloid precursor protein gene containing thyroid hormone receptor and Sp1 binding sites mediates negative regulation by 3,5,30-triiodothyronine","volume":"18","author":"Villa","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.neuint.2012.01.027","article-title":"Thyroid hormone regulation of APP (\u03b2-amyloid precursor protein) gene expression in brain and brain cultured cells","volume":"60","author":"Pascual","year":"2012","journal-title":"Neurochem. Int."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/2\/198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:56:17Z","timestamp":1760104577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/2\/198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":116,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["biom14020198"],"URL":"https:\/\/doi.org\/10.3390\/biom14020198","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,7]]}}}