Abstract
Thyroid hormones (THs) are essential and crucial for brain development, playing a role in growth and differentiation. Two globins named neuroglobin (Ngb) and cytoglobin (Cygb) are located in the brain, and each one has different distribution and function: They seem to have similar action by providing O2 for respiratory chain, and detoxification of reactive oxygen species (ROS) and nitric oxide (NO) protecting tissues against irreversible lesions. We aimed to investigate the influence of thyroid state in Ngb and Cygb metabolism in different brain regions and evaluate their responses in cerebellum, hippocampus and cerebral cortex (hereafter called as cortex) after supraphysiological doses at different time points of TH administration. Experiments were carried out in rats, divided in eight experimental groups Control (C), thyroidectomy (Tx), and thyroidectomy treated with jugular intravenous injection (i.v). T3 (100 μl/100 g) injection and sacrificed after 30, 60, 120 min and 6, 12 and 24 h. In cortex, we found increase in Ngb gene and protein expression in different time points compared to C group, however Cygb gene and protein expression were decreased. In hippocampus, Ngb and Cygb protein expression increased 24 h after i.v. T3 injection in comparison to Tx. In cerebellum, we found increased Ngb gene expression after 120 min, 6, 12 and 24 h after T3 administration compared to Tx, and in contrast, protein expression was found to be significantly increased only 12 and 24 h compared to Tx. Ngb and Cygb expression in brain is influenced by thyroid hormone state both by its lack or excess.
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References
Ahmed OM, El-Gareib AW, El-Bakry AM, El-Tawab SMA, Ahmed RG (2008) Thyroid hormone states and brain development interactions. Int J Dev Neurosci 26(7):825–826. doi:10.1016/j.ijdevneu.2008.09.003
Antao ST, Duong TTH, Aran R, Witting PK (2010) Neuroglobin overexpression in cultured human neuronal cells protects against hydrogen peroxide insult via activating phosphoinositide-3 kinase and opening the mitochondrial K-ATP channel. Antioxid Redox Signal 13(6):769–781. doi:10.1089/ars.2009.2977
Avivi A, Gerlach F, Joel A, Reuss S, Burmester T, Nevo E, Hankeln T (2010) Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat spalax. Proc Natl Acad Sci U S A 107(50):21570–21575. doi:10.1073/pnas.1015379107
Burmester T, Hankeln T (2004) Neuroglobin: a respiratory protein of the nervous system. News Physiol Sci 19:110–113. doi:10.1152/nips.01513.2003
Burmester T, Weich B, Reinhardt S, Hankeln T (2000) A vertebrate globin expressed in the brain. Nature 407(6803):520–523. doi:10.1038/35035093
Burmester T, Ebner B, Weich B, Hankeln T (2002) Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues. Mol Biol Evol 19(4):416–421
Burmester T, Gerlach F, Hankeln T (2007) Regulation and role of neuroglobin and cytoglobin under hypoxia. Hypoxia Circ 618:169–180
Cramer SC, Chopp M (2000) Recovery recapitulates ontogeny. Trends Neurosci 23(6):265–271. doi:10.1016/s0166-2236(00)01562-9
da Silva FG, Giannocco G, Santos MF, Nunes MT (2006) Thyroid hormone induction of actin polymerization in somatotrophs of hypothyroid rats: potential repercussions in growth hormone synthesis and secretion. Endocrinology 147(12):5777–5785. doi:10.1210/en.2006-0110
Di Liegro I (2008) Thyroid hormones and the central nervous system of mammals (review). Mol Med Rep 1(3):279–295
Farsetti A, Mitsuhashi T, Desvergne B, Robbins J, Nikodem VM (1991) Molecular-basis of thyroid-hormone regulation of myelin basic-protein gene-expression in rodent brain. J Biophys Chem 266(34):23226–23232
Fordel E, Thijs L, Martinet W, Schrijvers D, Moens L, Dewilde S (2007) Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions. Gene 398(1–2):114–122. doi:10.1016/j.gene.2007.03.022
Giannocco G, Dos Santos RA, Nunes MT (2004) Thyroid hormone stimulates myoglobin gene expression in rat cardiac muscle. Mol Cell Endocrinol 226(1–2):19–26. doi:10.1016/j.mce.2004.07.007
Greenberg DA, Jin K, Khan AA (2008) Neuroglobin: an endogenous neuroprotectant. Curr Opin Pharmacol 8(1):20–24. doi:10.1016/j.coph.2007.09.003
Hiroi Y, Huang ZH, Simoncini T, Limbourg FP, Gannon J, Moskowitz MA, Liao JK (2003) Stroke protection mediated by rapid, nongenomic actions of thyroid hormone. Circulation 108(17):253
Hundahl CA, Kelsen J, Hay-Schmidt A (2013) Neuroglobin and cytoglobin expression in the human brain. Brain Struct Funct 218(2):603–609. doi:10.1007/s00429-012-0480-8
Iniguez MA, Rodriguezpena A, Ibarrola N, Aguilera M, Munoz A, Bernal J (1993) Thyroid-hormone regulation of rc3, a brain-specific gene encoding a protein-kinase-c substrate. Endocrinology 133(2):467–473. doi:10.1210/en.133.2.467
Khan AA, Wang Y, Sun Y, Mao XO, Xie L, Miles E, Graboski J, Chen S, Ellerby LM, Jin K, Greenberg DA (2006) Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia. Proc Natl Acad Sci U S A 103(47):17944–17948. doi:10.1073/pnas.0607497103
Kim MK, Lee JS, Chung JH (1999) In vivo transcription factor recruitment during thyroid hormone receptor-mediated activation. Proc Natl Acad Sci U S A 96(18):10092–10097. doi:10.1073/pnas.96.18.10092
Laemmli UK (1970) Cleavage of structural proteins during assembly of head of bacteriophage-T4. Nature 227(5259):680–685. doi:10.1038/227680a0
Legrand C, Clos J, Legrand J (1982) Influence of altered thyroid and nutritional states on early histogenesis of the rat cerebellar cortex with special reference to synaptogenesis. Reprod Nutr Dev 22(1B):201–208. doi:10.1051/rnd:19820206
Leonard JL, Kaplan MM, Visser TJ, Silva JE, Larsen PR (1981) Cerebral-cortex responds rapidly to thyroid-hormones. Science 214(4520):571–573. doi:10.1126/science.7291997
Liu N, Yu Z, Li Y, Yuan J, Zhang J, Xiang S, Wang X (2013) Transcriptional regulation of mouse neuroglobin gene by cyclic AMP responsive element binding protein (CREB) in N2a cells. Neurosci Lett 534:333–337. doi:10.1016/j.neulet.2012.11.025
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biophys Chem 193(1):265–275
Manzano J, Bernal J, Morte B (2007) Influence of thyroid hormones on maturation of rat cerebellar astrocytes. Int J Dev Neurosci 25(3):171–179. doi:10.1016/j.ijdevneu.2007.01.003
Moeller LC, Dumitrescu AM, Walker RL, Meltzer PS, Refetoff S (2005) Thyroid hormone responsive genes in cultured human fibroblasts. J Clin Endocrinol Metab 90(2):936–943. doi:10.1210/jc.2004-1768
Moens L, Dewilde S (2000) Molecular physiology - globins in the brain. Nature 407(6803):461–462. doi:10.1038/35035181
Munoz A, Rodriguezpena A, Perezcastillo A, Ferreiro B, Sutcliffe JG, Bernal J (1991) Effects of neonatal-hypothyroidism on rat-brain gene-expression. Mol Endocrinol 5(2):273–280
Nedel Mendes-de-Aguiar CB, Alchini R, Decker H, Alvarez-Silva M, Tasca CI, Trentin AG (2008) Thyroid hormone increases astrocytic glutamate uptake and protects astrocytes and neurons against glutamate toxicity. J Neurosci Res 86(14):3117–3125. doi:10.1002/jnr.21755
Oppenheimer JH, Schwartz HL, Mariash CN, Kinlaw WB, Wong NCW, Freake HC (1987) Advances in our understanding of thyroid-hormone action at the cellular-level. Endocr Rev 8(3):288–308
Otto T, Fandrey J (2008) Thyroid hormone induces hypoxia-inducible factor 1 alpha gene expression through thyroid hormone receptor beta/retinoid X receptor alpha-dependent activation of hepatic leukemia factor. Endocrinology 149(5):2241–2250. doi:10.1210/en.2007-1238
Piosik PA, vanGroenigen M, Baas F (1996) Effect of thyroid hormone deficiency on RC3/neurogranin mRNA expression in the prenatal and adult caprine brain. Mol Brain Res 42(2):227–235. doi:10.1016/s0169-328x(96)00126-x
Purushothuman S, Stone J (2015) The reaction of cerebral cortex to a nearby lesion: damage, survival, self-protection. Brain Res 1601:52–63. doi:10.1016/j.brainres.2015.01.003
Rahaman SO, Ghosh S, Mohanakumar KP, Das S, Sarkar PK (2001) Hypothyroidism in the developing rat brain is associated with marked oxidative stress and aberrant intraneuronal accumulation of neurofilaments. Neurosci Res 40(3):273–279. doi:10.1016/s0168-0102(01)00237-1
Ramos HE, Weiss RE (2006) Regulation of nuclear coactivator and corepressor expression in mouse cerebellum by thyroid hormone. Thyroid 16(3):211–216. doi:10.1089/thy.2006.16.211
Reuss S, Saaler-Reinhardt S, Weich B, Wystub S, Reuss MH, Burmester T, Hankeln T (2002) Expression analysis of neuroglobin mRNA in rodent tissues. Neuroscience 115(3):645–656. doi:10.1016/s0306-4522(02)00536-5
Sharlin DS, Gilbert ME, Taylor MA, Ferguson DC, Zoeller RT (2010) The nature of the compensatory response to low thyroid hormone in the developing brain. J Neuroendocrinol 22(3):153–165. doi:10.1111/j.1365-2826.2009.01947.x
Sun YJ, Jin KL, Mao XO, Zhu YH, Greenberg DA (2001) Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury. Proc Natl Acad Sci U S A 98(26):15306–15311. doi:10.1073/pnas.251466698
Sun YJ, Jin KL, Peel A, Mao XO, Xie L, Greenberg DA (2003) Neuroglobin protects the brain from experimental stroke in vivo. Proc Natl Acad Sci U S A 100(6):3497–3500. doi:10.1073/pnas.0637726100
Woo SK, Kwon MS, Geng Z, Chen Z, Ivanov A, Bhatta S, Gerzanich V, Simard JM (2012) Sequential activation of hypoxia-inducible factor 1 and specificity protein 1 is required for hypoxia-induced transcriptional stimulation of Abcc8. J Cereb Blood Flow Metab 32(3):525–536. doi:10.1038/jcbfm.2011.159
Wystub S, Laufs T, Schmidt M, Burmester T, Maas U, Saaler-Reinhardt S, Hankeln T, Reuss S (2003) Localization of neuroglobin protein in the mouse brain. Neurosci Lett 346(1–2):114–116. doi:10.1016/s0304-3940(03)00563-9
Zhang CG, Wang CL, Deng MY, Li L, Wang HY, Fan M, Xu WL, Meng FW, Qian LJ, He FC (2002) Full-length cDNA cloning of human neuroglobin and tissue expression of rat neuroglobin. Biochem Biophys Res Commun 290(5):1411–1419. doi:10.1006/bbrc.2002.6360
Zivin JA (1998) Factors determining the therapeutic window for stroke. Neurology 50(3):599–603
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The authors disclose no actual or potential conflicts of interests.
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The present study was supported byFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) - grant # 2008/57,270–01.
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Oliveira, K.C., da Conceição, R.R., Piedade, G.C. et al. Thyroid hormone modulates neuroglobin and cytoglobin in rat brain. Metab Brain Dis 30, 1401–1408 (2015). https://doi.org/10.1007/s11011-015-9718-5
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DOI: https://doi.org/10.1007/s11011-015-9718-5