Metabolic Brain Disease

, Volume 27, Issue 2, pp 101–111 | Cite as

Thyroid hormone’s role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes

Review Article

Abstract

Cognitive performance is dependent on adequate glucose supply to the brain. Insulin, which regulates systemic glucose metabolism, has been recently shown both to regulate hippocampal metabolism and to be a mandatory component of hippocampally-mediated cognitive performance. Thyroid hormones (TH) regulate systemic glucose metabolism and may also be involved in regulation of brain glucose metabolism. Here we review potential mechanisms for such regulation. Importantly, TH imbalance is often encountered in combination with metabolic disorders such as diabetes, and may cause additional metabolic dysregulation and hence worsening of disease states. TH’s potential as a regulator of brain glucose metabolism is heightened by interactions with insulin signaling, but there have been relatively few studies on this topic or on the actions of TH in a mature brain. This review discusses evidence for mechanistic links between TH, insulin, cognitive function, and brain glucose metabolism, and reaches the conclusion that TH may modulate memory processes, likely at least in part by modulation of central insulin signaling and glucose metabolism.

Keywords

Insulin Thyroid hormone Diabetes GluT Glucose 

Notes

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

References

  1. Alzoubi KH, Alkadhi KA (2007) A critical role of CREB in the impairment of late-phase LTP by adult onset hypothyroidism. Exp Neurol 203(1):63–71PubMedGoogle Scholar
  2. Alzoubi KH et al (2007) Adult-onset hypothyroidism facilitates and enhances LTD: reversal by chronic nicotine treatment. Neurobiol Dis 26(1):264–272PubMedGoogle Scholar
  3. Alzoubi KH et al (2009) Levothyroxin restores hypothyroidism-induced impairment of hippocampus-dependent learning and memory: Behavioral, electrophysiological, and molecular studies. Hippocampus 19(1):66–78PubMedGoogle Scholar
  4. Babri A et al (2007) Intrahippocampal insulin improves memory in a passive-avoidance task in male wistar rats. Brain Cognit 64:86–91Google Scholar
  5. Bauer M et al (2009) Brain glucose metabolism in hypothyroidism: a positron emission tomography study before and after thyroid hormone replacement therapy. J Clin Endocrinol Metab 94(8):2922–2929PubMedGoogle Scholar
  6. Benedict C et al (2004) Intranasal insulin improves memory in humans. Psychoneuroendocrinology 29(10):1326–1334PubMedGoogle Scholar
  7. Benedict C et al (2007) Intranasal insulin improves memory in humans: superiority of insulin aspart. Neuropsychopharmacology 32(1):239–243PubMedGoogle Scholar
  8. Bergh JJ et al (2005) Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis. Endocrinology 146(7):2864–2871PubMedGoogle Scholar
  9. Bianco AC et al (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23(1):38–89PubMedGoogle Scholar
  10. Biessels GJ et al (2008) Cognition and diabetes: a lifespan perspective. Lancet Neurol 7(2):184–190PubMedGoogle Scholar
  11. Biondi B (2010) Thyroid and obesity: an intriguing relationship. J Clin Endocrinol Metab 95(8):3614–3617PubMedGoogle Scholar
  12. Brabant A et al (1989) The role of glucocorticoids in the regulation of thyrotropin. Acta Endocrinol (Copenh) 121(1):95–100Google Scholar
  13. Bradley DJ et al (1989) Differential expression of alpha and beta thyroid hormone receptor genes in rat brain and pituitary. Proc Natl Acad Sci U S A 86(18):7250–7254PubMedGoogle Scholar
  14. Brands AM et al (2007) Cognitive functioning and brain MRI in patients with type 1 and type 2 diabetes mellitus: a comparative study. Dement Geriatr Cogn Disord 23(5):343–350PubMedGoogle Scholar
  15. Canal C et al (2005) Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: modulation of learning rats and strategy selection. Learn Mem 12:367–374PubMedGoogle Scholar
  16. Canani LH et al (2005) The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 90(6):3472–3478PubMedGoogle Scholar
  17. Cano-Europa E et al (2008) Hypothyroidism induces selective oxidative stress in amygdala and hippocampus of rat. Metab Brain Dis 23(3):275–287PubMedGoogle Scholar
  18. Cao X et al (2009) Thyroid-hormone-dependent activation of the phosphoinositide 3-kinase/Akt cascade requires Src and enhances neuronal survival. Biochem J 424(2):201–209PubMedGoogle Scholar
  19. Carageorgiou H et al (2007) Changes in acetylcholinesterase, Na+, K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats. Metabolism 56(8):1104–1110PubMedGoogle Scholar
  20. Caria MA et al (2009) Thyroid hormone action: nongenomic modulation of neuronal excitability in the hippocampus. J Neuroendocrinol 21(2):98–107PubMedGoogle Scholar
  21. Casla A et al (1990) Increased glucose transporter (GLUT4) protein expression in hyperthyroidism. Biochem Biophys Res Commun 171(1):182–188PubMedGoogle Scholar
  22. Celani MF et al (1994) Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. Diabetes Res 27(1):15–25PubMedGoogle Scholar
  23. Cheng SY et al (2010) Molecular aspects of thyroid hormone actions. Endocr Rev 31(2):139–170PubMedGoogle Scholar
  24. Chiu SL, Cline HT (2010) Insulin receptor signaling in the development of neuronal structure and function. Neural Dev 5:7PubMedGoogle Scholar
  25. Chrousos GP (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332(20):1351–1362PubMedGoogle Scholar
  26. Chubb SA et al (2005a) Interactions among thyroid function, insulin sensitivity, and serum lipid concentrations: the Fremantle diabetes study. J Clin Endocrinol Metab 90(9):5317–5320PubMedGoogle Scholar
  27. Chubb SA et al (2005b) Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: the Fremantle Diabetes Study. Clin Endocrinol (Oxf) 62(4):480–486Google Scholar
  28. Constant EL et al (2001) Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. J Clin Endocrinol Metab 86(8):3864–3870PubMedGoogle Scholar
  29. Constantinou C et al (2005) Region-specific effects of hypothyroidism on the relative expression of thyroid hormone receptors in adult rat brain. Mol Cell Biochem 278(1–2):93–100PubMedGoogle Scholar
  30. Couch RM (1992) Dissociation of cortisol and adrenal androgen secretion in poorly controlled insulin-dependent diabetes mellitus. Acta Endocrinol (Copenh) 127(2):115–117Google Scholar
  31. Craft S et al (2011) Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol 69(1):29–38Google Scholar
  32. Custro N et al (1991) Changes in the thyroid hormone picture that may be found in severely decompensated type II diabetics. Minerva Med 82(1–2):9–14PubMedGoogle Scholar
  33. D’Arezzo S et al (2004) Rapid nongenomic effects of 3,5,3′-triiodo-L-thyronine on the intracellular pH of L-6 myoblasts are mediated by intracellular calcium mobilization and kinase pathways. Endocrinology 145(12):5694–5703PubMedGoogle Scholar
  34. Das K, Chainy GB (2004) Thyroid hormone influences antioxidant defense system in adult rat brain. Neurochem Res 29(9):1755–1766PubMedGoogle Scholar
  35. Davis PJ, Davis FB (2002) Nongenomic actions of thyroid hormone on the heart. Thyroid 12(6):459–466PubMedGoogle Scholar
  36. Davis PJ et al (2002) Comparison of the mechanisms of nongenomic actions of thyroid hormone and steroid hormones. J Endocrinol Invest 25(4):377–388PubMedGoogle Scholar
  37. De Felice FG et al (2009) Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A 106(6):1971–1976PubMedGoogle Scholar
  38. de Jong FJ et al (2006) Thyroid hormones, dementia, and atrophy of the medial temporal lobe. J Clin Endocrinol Metab 91(7):2569–2573PubMedGoogle Scholar
  39. Degroot A et al (2003) Glucose increases hippocampal extracellular acetylcholine levels upon activation of septal GABA receptors. Brain Res 979(1–2):71–77PubMedGoogle Scholar
  40. Desouza LA et al (2005) Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain. Mol Cell Neurosci 29(3):414–426PubMedGoogle Scholar
  41. Diez D et al (2008) Thyroid hormone action in the adult brain: gene expression profiling of the effects of single and multiple doses of triiodo-L-thyronine in the rat striatum. Endocrinology 149(8):3989–4000PubMedGoogle Scholar
  42. Diez JJ et al (2011) Prevalence of thyroid dysfunction in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 119(4):201–207PubMedGoogle Scholar
  43. Dimitriadis G et al (1985) Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am J Physiol 248(5 Pt 1):E593–E601PubMedGoogle Scholar
  44. Dora JM et al (2010) Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis. Eur J Endocrinol 163(3):427–434PubMedGoogle Scholar
  45. dos Reis EA et al (2002) Arginine administration inhibits hippocampal Na(+), K(+)-ATPase activity and impairs retention of an inhibitory avoidance task in rats. Brain Res 951(2):151–157PubMedGoogle Scholar
  46. Duick DS et al (1974) Effect of single dose dexamethasone on the concentration of serum triiodothyronine in man. J Clin Endocrinol Metab 39(6):1151–1154PubMedGoogle Scholar
  47. Erickson EJ et al (2006) Septal co-infusions of glucose with a GABAB agonist impair memory. Neurobiol Learn Mem 85(1):66–70PubMedGoogle Scholar
  48. Estivalet AA et al (2011) D2 Thr92Ala and PPARgamma2 Pro12Ala polymorphisms interact in the modulation of insulin resistance in type 2 diabetic patients. Obesity (Silver Spring) 19(4):825–832Google Scholar
  49. Fernandez-Lamo I et al (2009) Effects of thyroid hormone replacement on associative learning and hippocampal synaptic plasticity in adult hypothyroid rats. Eur J Neurosci 30(4):679–692PubMedGoogle Scholar
  50. Fliers E et al (2010) Novel neural pathways for metabolic effects of thyroid hormone. Trends Endocrinol Metab 21(4):230–236PubMedGoogle Scholar
  51. Freitas BC et al (2010) Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. J Clin Invest 120(6):2206–2217PubMedGoogle Scholar
  52. Garvey WT et al (1989) Expression of a glucose transporter gene cloned from brain in cellular models of insulin resistance: dexamethasone decreases transporter mRNA in primary cultured adipocytes. Mol Endocrinol 3(7):1132–1141PubMedGoogle Scholar
  53. Gavin LA et al (1981) The mechanism of impaired T3 production from T4 in diabetes. Diabetes 30(8):694–699PubMedGoogle Scholar
  54. Ge R et al (2010) 11beta-hydroxysteroid dehydrogenase type 1 inhibitors as promising therapeutic drugs for diabetes: status and development. Curr Med Chem 17(5):412–422PubMedGoogle Scholar
  55. Gereben B et al (2008a) Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev 29(7):898–938PubMedGoogle Scholar
  56. Gereben B et al (2008b) Activation and inactivation of thyroid hormone by deiodinases: local action with general consequences. Cell Mol Life Sci 65(4):570–590PubMedGoogle Scholar
  57. Gerges NZ, Alkadhi KA (2004) Hypothyroidism impairs late LTP in CA1 region but not in dentate gyrus of the intact rat hippocampus: MAPK involvement. Hippocampus 14(1):40–45PubMedGoogle Scholar
  58. Gerges NZ et al (2001) Combination of hypothyroidism and stress abolishes early LTP in the CA1 but not dentate gyrus of hippocampus of adult rats. Brain Res 922(2):250–260PubMedGoogle Scholar
  59. Gerges NZ et al (2005) Role of phosphorylated CaMKII and calcineurin in the differential effect of hypothyroidism on LTP of CA1 and dentate gyrus. Hippocampus 15(4):480–490PubMedGoogle Scholar
  60. Gerozissis K (2003) Brain insulin: regulation, mechanisms of action and functions. Cell Mol Neurobiol 23(1):1–25PubMedGoogle Scholar
  61. Gerozissis K (2008) Brain insulin, energy and glucose homeostasis; genes, environment and metabolic pathologies. Eur J Pharmacol 585(1):38–49PubMedGoogle Scholar
  62. Gerozissis K et al (2001) A potential role of central insulin in learning and memory related to feeding. Cell Mol Neurobiol 21(4):389–401PubMedGoogle Scholar
  63. Ghajar JB et al (1985) Regional acetylcholine metabolism in brain during acute hypoglycemia and recovery. J Neurochem 44(1):94–98PubMedGoogle Scholar
  64. Glass CK, Rosenfeld MG (2000) The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14(2):121–141PubMedGoogle Scholar
  65. Gold PE (1995) Role of glucose in regulating the brain and cognition. Am J Clin Nutr 61(4 Suppl):987S–995SPubMedGoogle Scholar
  66. Gold P (2005) Glucose and age-related changes in memory. Neurobiol Aging 26(1):60–64PubMedGoogle Scholar
  67. Gold SM et al (2007) Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia 50(4):711–719PubMedGoogle Scholar
  68. Gopinath B et al (2008) Type 2 diabetes does not predict incident thyroid dysfunction in the elderly. Diabetes Res Clin Pract 82(3):e11–e13PubMedGoogle Scholar
  69. Gorell JM et al (1981) Regional CNS levels of acetylcholine and choline during hypoglycemic stupor and recovery. J Neurochem 36(1):321–324PubMedGoogle Scholar
  70. Gould E et al (1991) The hippocampal formation: morphological changes induced by thyroid, gonadal and adrenal hormones. Psychoneuroendocrinology 16(1–3):67–84PubMedGoogle Scholar
  71. Grillo CA et al (2009) Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent. Brain Res 1296:35–45PubMedGoogle Scholar
  72. Grozovsky R et al (2009) Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes. Endocrinology 150(4):1976–1983PubMedGoogle Scholar
  73. Guadano-Ferraz A et al (1999) 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 19(9):3430–3439PubMedGoogle Scholar
  74. Guadano-Ferraz A et al (2003) Lack of thyroid hormone receptor alpha1 is associated with selective alterations in behavior and hippocampal circuits. Mol Psychiatry 8(1):30–38PubMedGoogle Scholar
  75. Hall J et al (1989) Glucose enhancement of performance on memory tests in young and aged humand. Neuropsychologia 27:1129–1138PubMedGoogle Scholar
  76. Handisurya A et al (2008) Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH). Clin Endocrinol (Oxf) 69(6):963–969Google Scholar
  77. Hassert DL et al (2004) The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala. Behav Neurosci 118(1):79–88PubMedGoogle Scholar
  78. Hernandez A et al (2010) Type 3 deiodinase deficiency causes spatial and temporal alterations in brain T3 signaling that are dissociated from serum thyroid hormone levels. Endocrinology 151(11):5550–5558PubMedGoogle Scholar
  79. Hogervorst E et al (2008) Thyroid function and cognitive decline in the MRC Cognitive Function and Ageing Study. Psychoneuroendocrinology 33(7):1013–1022PubMedGoogle Scholar
  80. Holmes C et al (1983) A survey of cognitive functioning at different glucose levels in diabetic persons. Diabetes Care 6:180–185PubMedGoogle Scholar
  81. Holmes C et al (1986) Simple versus complex impairments at three blood glucose levels. Psychoneuroendocrinology 11:353–357PubMedGoogle Scholar
  82. Holness MJ et al (2008) PPARalpha activation and increased dietary lipid oppose thyroid hormone signaling and rescue impaired glucose-stimulated insulin secretion in hyperthyroidism. Am J Physiol Endocrinol Metab 295(6):E1380–E1389PubMedGoogle Scholar
  83. Hoyland A et al (2008) Acute effects of macronutrient manipulations on cognitive test performance in healthy young adults: a systematic research review. Neurosci Biobehav Rev 32(1):72–85PubMedGoogle Scholar
  84. Iglesias T et al (1995) Identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) as a thyroid hormone regulated gene by whole genome PCR analysis. Biochem Biophys Res Commun 210(3):995–1000PubMedGoogle Scholar
  85. Ishay A et al (2009) Prevalence of subclinical hypothyroidism in women with type 2 diabetes. Med Sci Monit 15(4):CR151–CR155PubMedGoogle Scholar
  86. Izumi Y et al (2003) Effects of insulin on LTP in hippocampal slices from diabetic rats. Diabetologia 46(7):1007–1012PubMedGoogle Scholar
  87. Jolivalt CG et al (2010) Type 1 diabetes exaggerates features of Alzheimer’s disease in APP transgenic mice. Exp Neurol 223(2):422–431PubMedGoogle Scholar
  88. Klieverik LP et al (2008) Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats. Am J Physiol Endocrinol Metab 294(3):E513–E520PubMedGoogle Scholar
  89. Klieverik LP et al (2009) Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. Proc Natl Acad Sci U S A 106(14):5966–5971PubMedGoogle Scholar
  90. Korol DL, Gold PE (1998) Glucose, memory, and aging. Am J Clin Nutr 67(4):764S–771SPubMedGoogle Scholar
  91. Krebs-Kraft DL, Parent MB (2008) Hippocampal infusions of glucose reverse memory deficits produced by co-infusions of a GABA receptor agonist. Neurobiol Learn Mem 89(2):142–152PubMedGoogle Scholar
  92. Kuruvilla AK et al (1991) Regulation of glucose transport in Clone 9 cells by thyroid hormone. Biochim Biophys Acta 1094(3):300–308PubMedGoogle Scholar
  93. Lazar MA (1993) Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev 14(2):184–193PubMedGoogle Scholar
  94. Lechan RM et al (1993) Immunocytochemical delineation of thyroid hormone receptor beta 2-like immunoreactivity in the rat central nervous system. Endocrinology 132(6):2461–2469PubMedGoogle Scholar
  95. Lee MK et al (1988) Memory enhancement with posttraining intraventricular glucose injections in rats. Behav Neurosci 102(4):591–595PubMedGoogle Scholar
  96. Levin L et al (2004) Analysis of HLA genes in families with autoimmune diabetes and thyroiditis. Hum Immunol 65(6):640–647PubMedGoogle Scholar
  97. Li Q et al (2011) Common genetic variation in the 3′-untranslated region of gonadotropin-releasing hormone receptor regulates gene expression in cella and is associated with thyroid function, insulin secretion as well as insulin sensitivity in polycystic ovary syndrome patients. Hum Genet 129(5):553–561PubMedGoogle Scholar
  98. Lin JW et al (2000) Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization. Nat Neurosci 3(12):1282–1290PubMedGoogle Scholar
  99. Long J et al (1992) Complex maze performance in young and aged rats: response to glucose treatment and relationship to blood insulin and glucose. Physiol Behav 51:411–418PubMedGoogle Scholar
  100. LoPresti JS et al (1989) Alterations in 3,3′5′-triiodothyronine metabolism in response to propylthiouracil, dexamethasone, and thyroxine administration in man. J Clin Invest 84(5):1650–1656PubMedGoogle Scholar
  101. Man HY et al (2000) Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization.[erratum appears in Neuron 2001 Jan;29(1):307]. Neuron 25(3):649–662PubMedGoogle Scholar
  102. Manning CA et al (1998) Glucose enhancement of 24-h memory retrieval in healthy elderly humans. Behav Brain Res 93(1–2):71–76PubMedGoogle Scholar
  103. Matthaei S et al (1995) Effect of in vivo thyroid hormone status on insulin signalling and GLUT1 and GLUT4 glucose transport systems in rat adipocytes. J Endocrinol 144(2):347–357PubMedGoogle Scholar
  104. McEwen BS, Reagan LP (2004) Glucose transporter expression in the central nervous system: relationship to synaptic function. Eur J Pharmacol 490(1–3):13–24PubMedGoogle Scholar
  105. McNay EC, Gold PE (2002) Food for thought: fluctuations in brain extracellular glucose provide insight into the mechanisms of memory modulation. Behav Cogn Neurosci Rev 1(4):264–280PubMedGoogle Scholar
  106. McNay EC, Recknagel AK (2011) Brain insulin signaling: A key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes. Neurobiol Learn Mem 96(3):432–442Google Scholar
  107. McNay EC et al (2000) Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task. Proc Natl Acad Sci U S A 97(6):2881–2885PubMedGoogle Scholar
  108. McNay EC et al (2001) Fluctuations in brain glucose concentration during behavioral testing: dissociations between brain areas and between brain and blood. Neurobiol Learn Mem 75(3):325–337PubMedGoogle Scholar
  109. McNay EC et al (2004) Acute intrahippocampal insulin enhances spatial cognition, vol 888. Society for Neuroscience Annual Meeting, San Diego, Abstract 888.22Google Scholar
  110. McNay EC et al (2010) Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem 93(4):546–553PubMedGoogle Scholar
  111. Mentuccia D et al (2002) Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes 51(3):880–883PubMedGoogle Scholar
  112. Messier C (2004) Glucose improvement of memory: a review. Eur J Pharmacol 490(1–3):33–57PubMedGoogle Scholar
  113. Miao Q et al (2011) Reversible changes in brain glucose metabolism following thyroid function normalization in hyperthyroidism. AJNR Am J Neuroradiol 32(6):1034–1042PubMedGoogle Scholar
  114. Mielke J et al (2005) A biochemical and functional characterization of diet-induced brain insulin resistance. J Neurochem 93:1568–1578PubMedGoogle Scholar
  115. Mitsuhashi T et al (1988) Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. Proc Natl Acad Sci U S A 85(16):5804–5808PubMedGoogle Scholar
  116. Moeller LC et al (2006) Thyroid hormone mediated changes in gene expression can be initiated by cytosolic action of the thyroid hormone receptor beta through the phosphatidylinositol 3-kinase pathway. Nucl Recept Signal 4:e020PubMedGoogle Scholar
  117. Mooradian AD et al (1997) Thyroid hormone-induced GLUT-1 expression in rat cerebral tissue: effect of age. Brain Res 747(1):144–146PubMedGoogle Scholar
  118. Moosavi M et al (2006) The effect of intrahippocampal insulin microinjection on spatial learning and memory. Horm Behav 50:748–752PubMedGoogle Scholar
  119. Morrison CD et al (2010) High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling. J Neurochem 114(6):1581–1589PubMedGoogle Scholar
  120. Morteza Taghavi S et al (2011) Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism. Diab Vasc Dis Res 8(1):47–48PubMedGoogle Scholar
  121. Naeije R et al (1978) A low T3 syndrome in diabetic ketoacidosis. Clin Endocrinol (Oxf) 8(6):467–472Google Scholar
  122. O’Brien MD, Harris PW (1968) Cerebral-cortex perfusion-rates in myxoedema. Lancet 1(7553):1170–1172PubMedGoogle Scholar
  123. Pantos C et al (2004) Thyroid hormone and phenotypes of cardioprotection. Basic Res Cardiol 99(2):101–120PubMedGoogle Scholar
  124. Parsons MW, Gold PE (1992) Glucose enhancement of memory in elderly humans: an inverted-U dose-response curve. Neurobiol Aging 13(3):401–404PubMedGoogle Scholar
  125. Patti ME et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100(14):8466–8471PubMedGoogle Scholar
  126. Pedersen O et al (1988) Characterization of the insulin resistance of glucose utilization in adipocytes from patients with hyper- and hypothyroidism. Acta Endocrinol (Copenh) 119(2):228–234Google Scholar
  127. Peeters RP et al (2003) Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab 88(7):3202–3211PubMedGoogle Scholar
  128. Pelligrino D et al (1990) Brain glucose utilization and transport and cortical function in chronic vs. acute hypoglycemia. Am J Physiol 259:E729–E735PubMedGoogle Scholar
  129. Peter SA (1991) Remission of Graves’ disease with hyperthyroidism by a combination of glucocorticoids and antithyroid drugs. J Natl Med Assoc 83(3):261–264PubMedGoogle Scholar
  130. Petersen KF et al (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350(7):664–671PubMedGoogle Scholar
  131. Piroli GG et al (2007) Corticosterone impairs insulin-stimulated translocation of GLUT4 in the rat hippocampus. Neuroendocrinology 85(2):71–80PubMedGoogle Scholar
  132. Prinz PN et al (1999) Thyroid hormones: positive relationships with cognition in healthy, euthyroid older men. J Gerontol A Biol Sci Med Sci 54(3):M111–M116PubMedGoogle Scholar
  133. Puymirat J et al (1991) Immunocytochemical localization of thyroid hormone receptors in the adult rat brain. Thyroid 1(2):173–184PubMedGoogle Scholar
  134. Pych J et al (2005) Acetylcholine release in hippocampus and striatum during testing on a rewarded spontaneous alternation task. Neurobiol Learn Mem 84:93–101PubMedGoogle Scholar
  135. Radaideh AR et al (2004) Thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan. Saudi Med J 25(8):1046–1050PubMedGoogle Scholar
  136. Ragozzino ME et al (1998) Modulation of hippocampal acetylcholine release and spontaneous alternation scores by intrahippocampal glucose injections. J Neurosci 18(4):1595–1601PubMedGoogle Scholar
  137. Rao J et al (2006) Regulation of cerebral glucose metabolism. Minerva Endocrinol 31(2):149–158PubMedGoogle Scholar
  138. Rasgon N, Jarvik L (2004) Insulin resistance, affective disorders, and Alzheimer’s disease: review and hypothesis. J Gerontol A Biol Sci Med Sci 59(2):178–183, discussion 184-92PubMedGoogle Scholar
  139. Re RN et al (1976) The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin. J Clin Endocrinol Metab 43(2):338–346PubMedGoogle Scholar
  140. Reagan LP (2005) Neuronal insulin signal transduction mechanisms in diabetes phenotypes. Neurobiol Aging 26(Suppl 1):56–59PubMedGoogle Scholar
  141. Reagan LP (2011) Diabetes as a chronic metabolic stressor: Causes, consequences and clinical complications. Exp Neurol In Press, Corrected Proof.Google Scholar
  142. Reed L, Pangaro LN (1995) Physiology of thyroid gland. 1: Synthesis and release, iodine metabolism, binding and transport. In: Becker KL (ed) Principles and practice of endocrinology and metabolism, J.B. Lippincott Co, Philadelphia, p 2161Google Scholar
  143. Reger M et al (2006) Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging 27:451–458PubMedGoogle Scholar
  144. Reger MA et al (2008) Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 70(6):440–448PubMedGoogle Scholar
  145. Revill P et al (2006) Impaired insulin signaling and the pathogenesis of Alzheimer’s disease. Drugs Today (Barc) 42(12):785–790Google Scholar
  146. Ross AP et al (2009) A high fructose diet impairs spatial memory in male rats. Neurobiol Learn Mem 92(3):410–416PubMedGoogle Scholar
  147. Roubsanthisuk W et al (2006) Hyperthyroidism induces glucose intolerance by lowering both insulin secretion and peripheral insulin sensitivity. J Med Assoc Thai 89(Suppl 5):S133–S140PubMedGoogle Scholar
  148. Saini JS et al (1993) Thyroid hormones in diabetic ketoacidosis before and after therapy. J Assoc Physicians India 41(7):415–417PubMedGoogle Scholar
  149. Sala-Roca J et al (2008) Effects of adult dysthyroidism on the morphology of hippocampal neurons. Behav Brain Res 188(2):348–354PubMedGoogle Scholar
  150. Samuels MH (2000) Effects of variations in physiological cortisol levels on thyrotropin secretion in subjects with adrenal insufficiency: a clinical research center study. J Clin Endocrinol Metab 85(4):1388–1393PubMedGoogle Scholar
  151. Samuels MH (2008) Cognitive function in untreated hypothyroidism and hyperthyroidism. Curr Opin Endocrinol Diabetes Obes 15(5):429–433PubMedGoogle Scholar
  152. Santalucia T et al (2001) A novel functional co-operation between MyoD, MEF2 and TRalpha1 is sufficient for the induction of GLUT4 gene transcription. J Mol Biol 314(2):195–204PubMedGoogle Scholar
  153. Sato K, Robbins J (1981) Thyroid hormone metabolism in primary cultured rat hepatocytes. Effects of glucose, glucagon, and insulin. J Clin Invest 68(2):475–483PubMedGoogle Scholar
  154. Scheinberg P et al (1950) Correlative observations on cerebral metabolism and cardiac output in myxedema. J Clin Invest 29(9):1139–1146PubMedGoogle Scholar
  155. Shukla PK et al (2010) Prenatal thyroxine treatment disparately affects peripheral and amygdala thyroid hormone levels. Psychoneuroendocrinology 35(6):791–797PubMedGoogle Scholar
  156. Simpson IA et al (1994) Glucose transporters in mammalian brain. Biochem Soc Trans 22(3):671–675PubMedGoogle Scholar
  157. Sittig LJ et al (2011) Parent-of-origin allelic contributions to deiodinase-3 expression elicit localized hyperthyroid milieu in the hippocampus. Mol PsychiatryGoogle Scholar
  158. Smith CD, Ain KB (1995) Brain metabolism in hypothyroidism studied with 31P magnetic-resonance spectroscopy. Lancet 345(8950):619–620PubMedGoogle Scholar
  159. Smith JW et al (2002) Thyroid hormones, brain function and cognition: a brief review. Neurosci Biobehav Rev 26(1):45–60PubMedGoogle Scholar
  160. St Germain DL et al (2009) Minireview: defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology 150(3):1097–1107PubMedGoogle Scholar
  161. Starr VL, Convit A (2007) Diabetes, sugar-coated but harmful to the brain. Curr Opin Pharmacol 7(6):638–642PubMedGoogle Scholar
  162. Steen E et al (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease–is this type 3 diabetes? J Alzheimers Dis 7(1):63–80PubMedGoogle Scholar
  163. Stefani MR, Gold PE (2001) Intrahippocampal infusions of k-atp channel modulators influence spontaneous alternation performance: relationships to acetylcholine release in the hippocampus. J Neurosci 21(2):609–614PubMedGoogle Scholar
  164. Sui L et al (2005) Impairment in short-term but enhanced long-term synaptic potentiation and ERK activation in adult hippocampal area CA1 following developmental thyroid hormone insufficiency. Toxicol Sci 85(1):647–656PubMedGoogle Scholar
  165. Sui L et al (2006) Adult-onset hypothyroidism impairs paired-pulse facilitation and long-term potentiation of the rat dorsal hippocampo-medial prefrontal cortex pathway in vivo. Brain Res 1096(1):53–60PubMedGoogle Scholar
  166. Sui L et al (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(6):1065–1076PubMedGoogle Scholar
  167. Sun MK, Alkon DL (2006) Links between Alzheimer’s disease and diabetes. Drugs Today (Barc) 42(7):481–489Google Scholar
  168. Talley CP et al (2002) Vagotomy attenuates effects of L-glucose but not of D-glucose on spontaneous alternation performance. Physiol Behav 77(2–3):243–249PubMedGoogle Scholar
  169. Thompson CC, Potter GB (2000) Thyroid hormone action in neural development. Cereb Cortex 10(10):939–945PubMedGoogle Scholar
  170. Torrance CJ et al (1997) Characterization of a low affinity thyroid hormone receptor binding site within the rat GLUT4 gene promoter. Endocrinology 138(3):1215–1223PubMedGoogle Scholar
  171. Tsigos C, Chrousos GP (2002) Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 53(4):865–871PubMedGoogle Scholar
  172. Vallortigara J et al (2009) Thyroid hormone receptor alpha plays an essential role in the normalisation of adult-onset hypothyroidism-related hypoexpression of synaptic plasticity target genes in striatum. J Neuroendocrinol 21(1):49–56PubMedGoogle Scholar
  173. van den Berg E et al (2009) Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: A systematic comparison of their impact on cognition. Biochim Biophys Acta 1792(5):470–481PubMedGoogle Scholar
  174. van Raalte DH et al (2011) Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial. Diabetologia 54(8):2103–2112PubMedGoogle Scholar
  175. Vannucci SJ et al (1998) GLUT4 glucose transporter expression in rodent brain: effect of diabetes. Brain Res 797(1):1–11PubMedGoogle Scholar
  176. Venditti P, Di Meo S (2006) Thyroid hormone-induced oxidative stress. Cell Mol Life Sci 63(4):414–434PubMedGoogle Scholar
  177. Venero C et al (2005) Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor alpha1 can be ameliorated by T3 treatment. Genes Dev 19(18):2152–2163PubMedGoogle Scholar
  178. Vondra K et al (2005) Thyroid gland diseases in adult patients with diabetes mellitus. Minerva Endocrinol 30(4):217–236PubMedGoogle Scholar
  179. Wajchenberg BL et al (1984) Glucocorticoids, glucose metabolism and hypothalamic-pituitary-adrenal axis. Adv Exp Med Biol 171:25–44PubMedGoogle Scholar
  180. Walker DL et al (1991) Naloxone modulates the behavioral effects of cholinergic agonists and antagonists. Psychopharmacology 105(1):57–62PubMedGoogle Scholar
  181. Wang M (2011) Inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 in antidiabetic therapy. Handb Exp Pharmacol (203):127–146Google Scholar
  182. Watson GS, Craft S (2004) Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer's disease. Eur J Pharmacol 490(1–3):97–113PubMedGoogle Scholar
  183. Weinstein SP et al (1994) Thyroid hormone increases basal and insulin-stimulated glucose transport in skeletal muscle. The role of GLUT4 glucose transporter expression. Diabetes 43(10):1185–1189PubMedGoogle Scholar
  184. Wilber JF, Utiger RD (1969) The effect of glucocorticoids on thyrotropin secretion. J Clin Invest 48(11):2096–2103PubMedGoogle Scholar
  185. Wilcoxon JS et al (2007) Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha. Behav Brain Res 177(1):109–116PubMedGoogle Scholar
  186. Winocur G, Gagnon S (1998) Glucose treatment attenuates spatial learning and memory deficits of aged rats on tests of hippocampal function. Neurobiol Aging 19(3):233–241PubMedGoogle Scholar
  187. Wulf A et al (2008) T3-mediated expression of PGC-1alpha via a far upstream located thyroid hormone response element. Mol Cell Endocrinol 287(1–2):90–95PubMedGoogle Scholar
  188. Wyse AT et al (2004) Training in inhibitory avoidance causes a reduction of Na+, K+-ATPase activity in rat hippocampus. Physiol Behav 80(4):475–479PubMedGoogle Scholar
  189. Yasui S et al (2008) Insulin activates ATP-sensitive potassium channels via phosphatidylinositol 3-kinase in cultured vascular smooth muscle cells. J Vasc Res 45(3):233–243PubMedGoogle Scholar
  190. Zhao WQ et al (2004) Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 490(1–3):71–81PubMedGoogle Scholar
  191. Zhu DF et al (2011) Effect of thyroxine on synaptotagmin 1 and SNAP-25 expression in dorsal hippocampus of adult-onset hypothyroid rats. J Endocrinol InvestGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Office of Outcomes Assessment and Institutional ResearchExcelsior CollegeAlbanyUSA
  2. 2.Behavioral Neuroscience and Center for Neuroscience ResearchUniversity at Albany, SUNYAlbanyUSA

Personalised recommendations