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Striking neuronal thymosin beta 4 expression in the deep layers of the mouse superior colliculus after monocular deprivation

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Abstract

Thymosin beta 4 (Tβ4), a small acidic peptide isolated originally from calf thymus, is recognized as a regulator of actin polymerization. It is widely distributed in the brain, in neurons as well as in microglia, and it has been implicated in lesion-induced neuroplasticity. In the present study, we quantitatively analyzed the immunocytochemical expression pattern of Tβ4 in the superior colliculus (SC) of the adult mouse following monocular enucleation. Immunocytochemistry revealed a remarkable neuronal profile in the SC of 2, 5 and 7-week enucleated animals. We investigated the morphology, number and layer-specific localization of these immunoreactive neurons. Neuronal Tβ4-immunoreactive cell bodies were only sparsely found in the deep layers of the SC of control mice and showed only few and short immunoreactive branches, whereas their number increased significantly with post-enucleation survival time, as well as the total extent of the neuritic tree and its degree of branching. Occasionally, some Tβ4-immunoreactive neurons were also detected in the periaqueductal gray. As a regulator of actin metabolism, Tβ4 may influence the remodeling of these collicular neuronal processes, possibly in the context of a re-alignment of the sensory and motor maps in the deep SC as a consequence of the visual deprivation paradigm.

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References

  • Anadon R, Rodriguez M,I, Carpintero P, Evangelatos G, Livianou E, Leondiadis L, Quintela I, Cervino MC, Gomez-Marquez J (2001) Differential expression of thymosins beta(4) and beta(10) during rat cerebellum postnatal development. Brain Res 894:255–265

    Article  PubMed  CAS  Google Scholar 

  • Aronoff R, Matyas F, Mateo C, Ciron C, Schneider B, Petersen CC (2010) Long-range connectivity of mouse primary somatosensory barrel cortex. Eur J Neurosci 31:2221–2233

    Article  PubMed  Google Scholar 

  • Bajo VM, Nodal FR, Bizley JK, King AJ (2010) The non-lemniscal auditory cortex in ferrets: convergence of corticotectal inputs in the superior colliculus. Front Neuroanat 4:1–15

    Google Scholar 

  • Ballweber E, Hannappel E, Huff T, Stephan H, Haener M, Taschner N, Stoffler D, Aebi U, Mannherz HG (2002) Polymerisation of chemically cross-linked actin:thymosin beta(4) complex to filamentous actin: alteration in helical parameters and visualisation of thymosin beta(4) binding on F-actin. J Mol Biol 315:613–625

    Article  PubMed  CAS  Google Scholar 

  • Behan M, Appell PP (1992) Intrinsic circuitry in the cat superior colliculus: projections from the superficial layers. J Comp Neurol 315:230–243

    Article  PubMed  CAS  Google Scholar 

  • Border BG, Lin SC, Griffin WS, Pardue S, Morrison-Bogorad M (1993) Alterations in actin-binding beta-thymosin expression accompany neuronal differentiation and migration in rat cerebellum. J Neurochem 61:2104–2114

    Article  PubMed  CAS  Google Scholar 

  • Brainard MS, Knudsen EI (1993) Experience-dependent plasticity in the inferior colliculus: a site for visual calibration of the neural representation of auditory space in the barn owl. J Neurosci 13:4589–4608

    PubMed  CAS  Google Scholar 

  • Carpinterio P, Anadon R, del Amo FF, Gomez-Marquez J (1995) The thymosin beta 4 gene is strongly activated in neural tissues during early postimplantation mouse development. Neurosci Lett 184:63–66

    Article  PubMed  CAS  Google Scholar 

  • Carpintero P, Anadon R, Diaz-Regueira S, Gomez-Marquez J (1999) Expression of thymosin beta4 messenger RNA in normal and kainate-treated rat forebrain. Neuroscience 90:1433–1444

    Article  PubMed  CAS  Google Scholar 

  • Ceuppens R, Dumont D, Van Brussel L, Van de Plas B, Daniels R, Noben J-P, Verhaert P, Van der Gucht E, Robben J, Clerens S, Arckens L (2007) Direct profiling of myelinated and demyelinated regions in mouse brain by mass spectrometry imaging. Int J Mass Spectrom 260:185–194

    Article  CAS  Google Scholar 

  • Cha HJ, Jeong MJ, Kleinman HK (2003) Role of thymosin beta4 in tumor metastasis and angiogenesis. J Natl Cancer Inst 95:1674–1680

    Article  PubMed  CAS  Google Scholar 

  • Choi SY, Noh MR, Kim DK, Sun W, Kim H (2007) Neuroprotective function of thymosin-beta and its derivative peptides on the programmed cell death of chick and rat neurons. Biochem Biophys Res Commun 362:587–593

    Article  PubMed  CAS  Google Scholar 

  • Cuyvers A, Paulussen M, Smolders K, Hu T-T, Arckens L (2010) Local cell proliferation upon enucleation in direct retinal brain targets in the visual system of the adult mouse. J Exp Neurosci 4:1–15

    Article  CAS  Google Scholar 

  • Dedova IV, Nikolaeva OP, Safer D, De La Cruz EM, dos Remedios CG (2006) Thymosin beta4 induces a conformational change in actin monomers. Biophys J 90:985–992

    Article  PubMed  CAS  Google Scholar 

  • Dong JH, Ying GX, Liu X, Wang WY, Wang Y, Ni ZM, Zhou CF (2005) Expression of thymosin beta4 mRNA by activated microglia in the denervated hippocampus. Neuroreport 16:1629–1633

    Article  PubMed  CAS  Google Scholar 

  • Dräger UC, Hubel DH (1975) Physiology of visual cells in mouse superior colliculus and correlation with somatosensory and auditory input. Nature 253:203–204

    Article  PubMed  Google Scholar 

  • Dräger UC, Hubel DH (1976) Topography of visual and somatosensory projections to mouse superior colliculus. J Neurophysiol 39:91–101

    PubMed  Google Scholar 

  • Erickson-Viitanen S, Ruggieri S, Natalini P, Horecker BL (1983) Distribution of thymosin beta 4 in vertebrate classes. Arch Biochem Biophys 221:570–576

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Marquez J, Anadon R (2002) The beta-thymosins, small actin-binding peptides widely expressed in the developing and adult cerebellum. Cerebellum 1:95–102

    Article  PubMed  CAS  Google Scholar 

  • Grant DS, Kinsella JL, Kibbey MC, LaFlamme S, Burbelo PD, Goldstein AL, Kleinman HK (1995) Matrigel induces thymosin beta 4 gene in differentiating endothelial cells. J Cell Sci 108(Pt 12):3685–3694

    PubMed  CAS  Google Scholar 

  • Grant DS, Rose W, Yaen C, Goldstein A, Martinez J, Kleinman H (1999) Thymosin beta4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis 3:125–135

    Article  PubMed  CAS  Google Scholar 

  • Hatada Y, Wu F, Silverman R, Schacher S, Goldberg DJ (1999) En passant synaptic varicosities form directly from growth cones by transient cessation of growth cone advance but not of actin-based motility. J Neurobiol 41:242–251

    Article  PubMed  CAS  Google Scholar 

  • Hatada Y, Wu F, Sun ZY, Schacher S, Goldberg DJ (2000) Presynaptic morphological changes associated with long-term synaptic facilitation are triggered by actin polymerization at preexisting varicositis. J Neurosci 20:RC82

    PubMed  CAS  Google Scholar 

  • Kim Y, Kim EH, Hong S, Rhyu IJ, Choe J, Sun W, Kim H (2006) Expression of thymosin beta in the rat brain following transient global ischemia. Brain Res 1085:177–182

    Article  PubMed  CAS  Google Scholar 

  • Kudo M (1981) Projections of the nuclei of the lateral lemniscus in the cat: an autoradiographic study. Brain Res 221:57–69

    Article  PubMed  CAS  Google Scholar 

  • Leonard DG, Ziff EB, Greene LA (1987) Identification and characterization of mRNAs regulated by nerve growth factor in PC12 cells. Mol Cell Biol 7:3156–3167

    PubMed  CAS  Google Scholar 

  • Low TL, Goldstein AL (1982) Chemical characterization of thymosin beta 4. J Biol Chem 257:1000–1006

    PubMed  CAS  Google Scholar 

  • Low TL, Hu SK, Goldstein AL (1981) Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci USA 78:1162–1166

    Article  PubMed  CAS  Google Scholar 

  • Malkinson G, Spira ME (2010) Clustering of excess growth resources within leading growth cones underlies the recurrent “deposition” of varicosities along developing neurites. Exp Neurol 225:140–153

    Article  PubMed  Google Scholar 

  • Mana S, Chevalier G (2001) Honeycomb-like structure of the intermediate layers of the rat superior colliculus: afferent and efferent connections. Neuroscience 103:673–693

    Article  PubMed  CAS  Google Scholar 

  • Mooney RD, Nikoletseas MM, Hess PR, Allen Z, Lewin AC, Rhoades RW (1988) The projection from the superficial to the deep layers of the superior colliculus: an intracellular horseradish peroxidase injection study in the hamster. J Neurosci 8(4):1384–1399

    PubMed  CAS  Google Scholar 

  • Morris DC, Chopp M, Zhang L, Zhang ZG (2010) Thymosin beta4: a candidate for treatment of stroke? Ann N Y Acad Sci 1194:112–117

    Article  PubMed  CAS  Google Scholar 

  • Paulussen M, Landuyt B, Schoofs L, Luyten W, Arckens L (2009) Thymosin beta 4 mRNA and peptide expression in phagocytic cells of different mouse tissues. Peptides 30:1822–1832

    Article  PubMed  CAS  Google Scholar 

  • Safer D, Elzinga M, Nachmias VT (1991) Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable. J Biol Chem 266:4029–4032

    PubMed  CAS  Google Scholar 

  • Saldaña E, Viñuela A, Marshall AF, Fitzpatrick DC, Aparicio MA (2007) The TLC: a novel auditory nucleus of the mammalian brain. J Neurosci 27(48):13108–13116

    Article  PubMed  Google Scholar 

  • Shu SY, Ju G, Fan LZ (1988) The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system. Neurosci Lett 85:169–171

    Article  PubMed  CAS  Google Scholar 

  • Smart N, Rossdeutsch A, Riley PR (2007) Thymosin beta4 and angiogenesis: modes of action and therapeutic potential. Angiogenesis 10:229–241

    Article  PubMed  CAS  Google Scholar 

  • Sparks DL (1988) Saccadic command signals in the superior colliculus: implications for sensorimotor transformations. Can J Physiol Pharmacol 66:527–531

    Article  PubMed  CAS  Google Scholar 

  • Stein BE, Meredith MA (1990) Multisensory integration. Neural and behavioral solutions for dealing with stimuli from different sensory modalities. Ann N Y Acad Sci 608:51–65

    Article  PubMed  CAS  Google Scholar 

  • Stein BE, Meredith MA (1991) Functional organization of the superior colliculus. In: Leventhal AG (ed) The neural basis of visual function. MacMillan, Basingstoke, pp 85–110

    Google Scholar 

  • Sternberger LA, Sternberger NH (1983) Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA 80(19):6126–6130

    Google Scholar 

  • Van Brussel L, Gerits A, Arckens L (2009) Identification and localization of functional subdivisions in the visual cortex of the adult mouse. J Comp Neurol 514:107–116

    Article  PubMed  Google Scholar 

  • Van Brussel L, Gerits A, Arckens L (2011) Evidence for cross-modal plasticity in adult mouse visual cortex following monocular enucleation. Cereb Cortex [Epub ahead of print]

  • Van der Gucht E, Hof PR, Van Brussel L, Burnat K, Arckens L (2007) Neurofilament protein and neuronal activity markers define regional architectonic parcellation in the mouse visual cortex. Cereb Cortex 17:2805–2819

    Article  PubMed  Google Scholar 

  • Van Kesteren RE, Carter C, Dissel HM, Van Minnen J, Gouwenberg Y, Syed NI, Spencer GE, Smit AB (2006) Local synthesis of actin-binding protein beta-thymosin regulates neurite outgrowth. J Neurosci 26:152–157

    Google Scholar 

  • Vartiainen N, Pyykonen I, Hokfelt T, Koistinaho J (1996) Induction of thymosin beta(4) mRNA following focal brain ischemia. Neuroreport 7:1613–1616

    Article  PubMed  CAS  Google Scholar 

  • Viñuela A, Aparicio MA, Berrebi AS, Saldaña E (2011) Connections of the Superior Paraolivary Nucleus of the Rat: II. Reciprocal Connections with the Tectal Longitudinal Column. Front Neuroanat 22(5):1

    Google Scholar 

  • Wurtz RH, Goldberg ME (1972) The role of the superior colliculus in visually-evoked eye movements. Bibl Ophthalmol 82:149–158

    PubMed  CAS  Google Scholar 

  • Xiong Y, Mahmood A, Meng Y, Zhang Y, Zhang ZG, Morris DC, Chopp M (2010) Treatment of traumatic brain injury with thymosin beta(4) in rats. J Neurosurg 114(1):102–115

    PubMed  Google Scholar 

  • Yang H, Cheng X, Yao Q, Li J, Ju G (2008) The promotive effects of thymosin beta4 on neuronal survival and neurite outgrowth by upregulating L1 expression. Neurochem Res 33:2269–2280

    Article  PubMed  CAS  Google Scholar 

  • Yoshida T, Kurella M, Beato F, Min H, Ingelfinger JR, Stears RL, Swinford RD, Gullans SR, Tang SS (2002) Monitoring changes in gene expression in renal ischemia-reperfusion in the rat. Kidney Int 61:1646–1654

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Zhang ZG, Morris D, Li Y, Roberts C, Elias SB, Chopp M (2009) Neurological functional recovery after thymosin beta4 treatment in mice with experimental auto encephalomyelitis. Neuroscience 164:1887–1893

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Inge Van der Auwera and Ria Van Laer for their excellent technical assistance and Dr. Estel Van der Gucht and Dr. Tjing-Tjing Hu for the critical revision of the manuscript. This work was supported by grants from the Fund for Scientific Research-Flanders (FWO) and the Research Fund of the Katholieke Universiteit Leuven, Belgium (OT 09/22).

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  1. Laboratory of Neuroplasticity and Neuroproteomics, Katholieke Universiteit Leuven, Naamsestraat 59, 3000, Leuven, Belgium

    Melissa Paulussen & Lutgarde Arckens

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  1. Melissa Paulussen
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  2. Lutgarde Arckens
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Correspondence to Lutgarde Arckens.

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Paulussen, M., Arckens, L. Striking neuronal thymosin beta 4 expression in the deep layers of the mouse superior colliculus after monocular deprivation. Brain Struct Funct 217, 81–91 (2012). https://doi.org/10.1007/s00429-011-0330-0

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