The effect of glial fibrillary acidic protein expression on neurite outgrowth from retinal explants in a permissive environment

BMC Research Notes

Robert W Nickells³  Albee Messing¹  Tracy L Hagemann¹  Kimberly A Toops² 

[1] The Waisman Center, University of Wisconsin, Madison, WI, 53706, USA;Departments of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, 53706, USA;Medical Sciences Center, 1300 University Avenue, Madison, WI, 53706-1532, USA

关键词: Retinal ganglion cell;    Axon regeneration;    Glial fibrillary acidic protein;   

Others  :  1165018
DOI  :  10.1186/1756-0500-5-693

 received in 2012-07-25, accepted in 2012-12-18,  发布年份 2012

【 摘 要 】

Background

Increased expression of glial fibrillary acidic protein (GFAP) within macroglia is commonly seen as a hallmark of glial activation after damage within the central nervous system, including the retina. The increased expression of GFAP in glia is also considered part of the pathologically inhibitory environment for regeneration of axons from damaged neurons. Recent studies have raised the possibility that reactive gliosis and increased GFAP cannot automatically be assumed to be negative events for the surrounding neurons and that the context of the reactive gliosis is critical to whether neurons benefit or suffer. We utilized transgenic mice expressing a range of Gfap to titrate the amount of GFAP in retinal explants to investigate the relationship between GFAP concentration and the regenerative potential of retinal ganglion cells.

Findings

Explants from Gfap^-/- and Gfap^+/- mice did not have increased neurite outgrowth compared with Gfap^+/+ or Gfap over-expressing mice as would be expected if GFAP was detrimental to axon regeneration. In fact, Gfap over-expressing explants had the most neurite outgrowth when treated with a neurite stimulatory media. Transmission electron microscopy revealed that neurites formed bundles, which were surrounded by larger cellular processes that were GFAP positive indicating a close association between growing axons and glial cells in this regeneration paradigm.

Conclusions

We postulate that glial cells with increased Gfap expression support the elongation of new neurites from retinal ganglion cells possibly by providing a scaffold for outgrowth.

【 授权许可】

   
2012 Toops et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Bringmann A, Pannicke T, Grosche J, Francke M, Wiedemann P, Skatchkov SN, Osborne NN, Reichenbach A: Muller cells in the healthy and diseased retina. Prog Retin Eye Res 2006, 25:397-424.
• [2]Sofroniew MV: Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 2009, 32:638-647.
• [3]Sofroniew MV, Vinters HV: Astrocytes: biology and pathology. Acta Neuropathol 2010, 119:7-35.
• [4]Dheen ST, Kaur C, Ling EA: Microglial activation and its implications in the brain diseases. Curr Med Chem 2007, 14:1189-1197.
• [5]Eddleston M, Mucke L: Molecular profile of reactive astrocytes-implications for their role in neurologic disease. Neuroscience 1993, 54:15-36.
• [6]Garcia DM, Koke JR: Astrocytes as gate-keepers in optic nerve regeneration-a mini-review. Comp Biochem Physiol A Mol Integr Physiol 2009, 152:135-138.
• [7]Benowitz LI, Yin Y: Optic nerve regeneration. Arch Ophthalmol 2010, 128:1059-1064.
• [8]Berry M, Ahmed Z, Lorber B, Douglas M, Logan A: Regeneration of axons in the visual system. Restor Neurol Neurosci 2008, 26:147-174.
• [9]Chen H, Weber AJ: Expression of glial fibrillary acidic protein and glutamine synthetase by Muller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factor. Glia 2002, 38:115-125.
• [10]Chun MH, Ju WK, Kim KY, Lee MY, Hofmann HD, Kirsch M, Oh SJ: Upregulation of ciliary neurotrophic factor in reactive Muller cells in the rat retina following optic nerve transection. Brain Res 2000, 868:358-362.
• [11]Lam TT, Kwong JM, Tso MO: Early glial responses after acute elevated intraocular pressure in rats. Invest Ophthalmol Vis Sci 2003, 44:638-645.
• [12]Lewis GP, Fisher SK: Up-regulation of glial fibrillary acidic protein in response to retinal injury: its potential role in glial remodeling and a comparison to vimentin expression. Int Rev Cytol 2003, 230:263-290.
• [13]Ramirez AI, Salazar JJ, de Hoz R, Rojas B, Gallego BI, Salinas-Navarro M, Alarcon-Martinez L, Ortin-Martinez A, Aviles-Trigueros M, Vidal-Sanz M, et al.: Quantification of the effect of different levels of IOP in the astroglia of the rat retina ipsilateral and contralateral to experimental glaucoma. Invest Ophthalmol Vis Sci 2010, 51:5690-5696.
• [14]Wang X, Tay SS, Ng YK: An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma. Exp Brain Res 2000, 132:476-484.
• [15]Ganesh BS, Chintala SK: Inhibition of reactive gliosis attenuates excitotoxicity-mediated death of retinal ganglion cells. PLoS One 2011, 6:e18305.
• [16]Vazquez-Chona FR, Swan A, Ferrell WD, Jiang L, Baehr W, Chien WM, Fero M, Marc RE, Levine EM: Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function. BMC Neuroscience 2011, 12:98. BioMed Central Full Text
• [17]Lorber B, Guidi A, Fawcett JW, Martin KR: Activated retinal glia mediated axon regeneration in experimental glaucoma. Neurobiology of Disease 2012, 45:243-252.
• [18]Stafford CA, Shehab SA, Nona SN, Cronly-Dillon JR: Expression of glial fibrillary acidic protein (GFAP) in goldfish optic nerve following injury. Glia 1990, 3:33-42.
• [19]Lang DM, del Mar Romero-Aleman M, Arbelo-Galvan JF, Stuermer CA, Monzon-Mayor M: Regeneration of retinal axons in the lizard Gallotia galloti is not linked to generation of new retinal ganglion cells. J Neurobiol 2002, 52:322-335.
• [20]Arenzana FJ, Santos-Ledo A, Porteros A, Aijon J, Velasco A, Lara JM, Arevalo R: Characterisation of neuronal and glial populations of the visual system during zebrafish lifespan. Int J Dev Neurosci 2011, 29:441-449.
• [21]Barresi MJ, Burton S, Dipietrantonio K, Amsterdam A, Hopkins N, Karlstrom RO: Essential genes for astroglial development and axon pathfinding during zebrafish embryogenesis. Dev Dyn 2010, 239:2603-2618.
• [22]Rozovsky I, Wei M, Morgan TE, Finch CE: Reversible age impairments in neurite outgrowth by manipulations of astrocytic GFAP. Neurobiol Aging 2005, 26:705-715.
• [23]Menet V, Gimenez YRM, Sandillon F, Privat A: GFAP null astrocytes are a favorable substrate for neuronal survival and neurite growth. Glia 2000, 31:267-272.
• [24]Menet V, Gimenez y Ribotta M, Chauvet N, Drian MJ, Lannoy J, Colucci-Guyon E, Privat A: Inactivation of the glial fibrillary acidic protein gene, but not that of vimentin, improves neuronal survival and neurite growth by modifying adhesion molecule expression. J Neurosci 2001, 21:6147-6158.
• [25]Lefrancois T, Fages C, Peschanski M, Tardy M: Neuritic outgrowth associated with astroglial phenotypic changes induced by antisense glial fibrillary acidic protein (GFAP) mRNA in injured neuron-astrocyte cocultures. J Neurosci 1997, 17:4121-4128.
• [26]Kinouchi R, Takeda M, Yang L, Wilhelmsson U, Lundkvist A, Pekny M, Chen DF: Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nature neuroscience 2003, 6:863-868.
• [27]Wang X, Messing A, David S: Axonal and nonneuronal cell responses to spinal cord injury in mice lacking glial fibrillary acidic protein. Exp Neurol 1997, 148:568-576.
• [28]Heiduschka P, Thanos S: Cortisol promotes survival and regeneration of axotomised retinal ganglion cells and enhances effects of aurintricarboxylic acid. Graefes Arch Clin Exp Ophthalmol 2006, 244:1512-1521.
• [29]Lorber B, Berry M, Douglas MR, Nakazawa T, Logan A: Activated retinal glia promote neurite outgrowth of retinal ganglion cells via apolipoprotein E. J Neurosci Res 2009, 87:2645-2652.
• [30]Toops KA, Berlinicke C, Zack DJ, Nickells RW: Hydrocortisone stimulates neurite outgrowth from mouse retinal explants by modulating macroglial activity. Invest Ophthalmol Visual Sci 2012, 53:2046-2061.
• [31]McCall MA, Gregg RG, Behringer RR, Brenner M, Delaney CL, Galbreath EJ, Zhang CL, Pearce RA, Chiu SY, Messing A: Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proc Natl Acad Sci U S A 1996, 93:6361-6366.
• [32]Manthorpe M, Cornefert-Jensen F, Hartikka J, Felgner J, Rundell A, Margalith M, Dwarki V: Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum Gene Ther 1993, 4:419-431.
• [33]Petzold A, Keir G, Green AJ, Giovannoni G, Thompson EJ: An ELISA for glial fibrillary acidic protein. J Immunol Methods 2004, 287:169-177.
• [34]Hogan MJ, Alvarado J, Weddell JE: Ultrastructure of the Eye. In Histology of the Human Eye. Philadelphia, PA: WB Saunder Company; 1971.
• [35]Middeldorp J, Hol EM: GFAP in health and disease. Prog Neurobiol 2011, 93:421-443.
• [36]Sullivan SM, Lee A, Bjorkman ST, Miller SM, Sullivan RK, Poronnik P, Colditz PB, Pow DV: Cytoskeletal anchoring of GLAST determines susceptibility to brain damage: an identified role for GFAP. J Biol Chem 2007, 282:29414-29423.
• [37]Hanbury R, Ling ZD, Wuu J, Kordower JH: GFAP knockout mice have increased levels of GDNF that protect striatal neurons from metabolic and excitotoxic insults. J Comp Neurol 2003, 461:307-316.
• [38]Gomes FC, Paulin D, Moura Neto V: Glial fibrillary acidic protein (GFAP): modulation by growth factors and its implication in astrocyte differentiation. Braz J Med Biol Res 1999, 32:619-631.
• [39]Hidalgo A: Neuron-glia interactions during axon guidance in Drosophila. Biochem Soc Trans 2003, 31:50-55.
• [40]Marcus RC, Easter SS Jr: Expression of glial fibrillary acidic protein and its relation to tract formation in embryonic zebrafish (Danio rerio). J Comp Neurol 1995, 359:365-381.
• [41]Gingras M, Bergeron J, Dery J, Durham HD, Berthod F: In vitro development of a tissue-engineered model of peripheral nerve regeneration to study neurite growth. Faseb J 2003, 17:2124-2126.
• [42]Pfeifer K, Vroemen M, Blesch A, Weidner N: Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury. Eur J Neurosci 2004, 20:1695-1704.
• [43]Xue L, Ding P, Xiao L, Hu M, Hu Z: Nestin, a new marker, expressed in Muller cells following retinal injury. Can J Neurol Sci 2010, 37:643-649.