Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

Journal of Neuroinflammation

Colin J Saldanha¹  Kelli A Duncan¹ 

[1] Department of Biological Sciences, Lehigh University, 111 Research Dr., Bethlehem, Pennsylvania, 18015, USA

关键词: Glia;    Neuroinflammation;    Estrogen;    Cytokine;    Aromatase;   

Others  :  1213253
DOI  :  10.1186/1742-2094-8-81

 received in 2011-05-24, accepted in 2011-07-18,  发布年份 2011

【 摘 要 】

Background

Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown.

Methods

Adult male zebra finches (Taeniopygia guttata) were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA), an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test.

Results

Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression.

Conclusions

These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

【 授权许可】

   
2011 Duncan and Saldanha; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Peterson RS, Lee DW, Fernando G, Schlinger BA: Radial glia express aromatase in the injured zebra finch brain. J Comp Neurol 2004, 475:261-269.
• [2]Azcoitia I, Sierra A, Veiga S, Garcia-Segura LM: Aromatase expression by reactive astroglia is neuroprotective. Ann N Y Acad Sci 2003, 1007:298-305.
• [3]Saldanha CJ, Duncan KA, Walters BJ: Neuroprotective actions of brain aromatase. Front Neuroendocrinol 2009, 30:106-118.
• [4]Saldanha CJ, Popper P, Micevych PE, Schlinger BA: The passerine hippocampus is a site of high aromatase: inter- and intraspecies comparisons. Horm Behav 1998, 34:85-97.
• [5]Shen P, Schlinger BA, Campagnoni AT, Arnold AP: An atlas of aromatase mRNA expression in the zebra finch brain. J Comp Neurol 1995, 360:172-184.
• [6]Schlinger BA, Amur-Umarjee S, Shen P, Campagnoni AT, Arnold AP: Neuronal and non-neuronal aromatase in primary cultures of developing zebra finch telencephalon. J Neurosci 1994, 14:7541-7552.
• [7]Wynne RD, Saldanha CJ: Glial aromatization decreases neural injury in the zebra finch (Taeniopygia guttata): influence on apoptosis. J Neuroendocrinol 2004, 16:676-683.
• [8]Peterson RS, Saldanha CJ, Schlinger BA: Rapid upregulation of aromatase mRNA and protein following neural injury in the zebra finch (Taeniopygia guttata). J Neuroendocrinol 2001, 13:317-323.
• [9]Garcia-Segura LM, Wozniak A, Azcoitia I, Rodriguez JR, Hutchison RE, Hutchison JB: Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience 1999, 89:567-578.
• [10]Azcoitia I, Garcia-Ovejero D, Chowen JA, Garcia-Segura LM: Astroglia play a key role in the neuroprotective actions of estrogen. Prog Brain Res 2001, 132:469-478.
• [11]Wynne RD, Walters BJ, Bailey DJ, Saldanha CJ: Inhibition of injury-induced glial aromatase reveals a wave of secondary degeneration in the songbird brain. Glia 2008, 56:97-105.
• [12]Wise PM, Dubal DB, Wilson ME, Rau SW, Bottner M: Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action. Endocrinology 2001, 142:969-973.
• [13]Azcoitia I, Sierra A, Veiga S, Honda S, Harada N, Garcia-Segura LM: Brain aromatase is neuroprotective. J Neurobiol 2001, 47:318-329.
• [14]Arevalo MA, Santos-Galindo M, Bellini MJ, Azcoitia I, Garcia-Segura LM: Actions of estrogens on glial cells: Implications for neuroprotection. Biochim Biophys Acta 2009.
• [15]Wise P: Estradiol exerts neuroprotective actions against ischemic brain injury: insights derived from animal models. Endocrine 2003, 21:11-15.
• [16]DeLegge MH, Smoke A: Neurodegeneration and inflammation. Nutr Clin Pract 2008, 23:35-41.
• [17]Lucas SM, Rothwell NJ, Gibson RM: The role of inflammation in CNS injury and disease. Br J Pharmacol 2006, 147(Suppl 1):S232-240.
• [18]Allan SM, Rothwell NJ: Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001, 2:734-744.
• [19]Ghirnikar RS, Lee YL, Eng LF: Inflammation in traumatic brain injury: role of cytokines and chemokines. Neurochem Res 1998, 23:329-340.
• [20]Simi A, Tsakiri N, Wang P, Rothwell NJ: Interleukin-1 and inflammatory neurodegeneration. Biochem Soc Trans 2007, 35:1122-1126.
• [21]Rothwell NJ, Strijbos PJ: Cytokines in neurodegeneration and repair. Int J Dev Neurosci 1995, 13:179-185.
• [22]Marciano PG, Eberwine JH, Ragupathi R, Saatman KE, Meaney DF, McIntosh TK: Expression profiling following traumatic brain injury: a review. Neurochem Res 2002, 27:1147-1155.
• [23]Lenzlinger PM, Morganti-Kossmann MC, Laurer HL, McIntosh TK: The duality of the inflammatory response to traumatic brain injury. Mol Neurobiol 2001, 24:169-181.
• [24]Allan SM, Rothwell NJ: Inflammation in central nervous system injury. Philos Trans R Soc Lond B Biol Sci 2003, 358:1669-1677.
• [25]Van Eldik LJ, Thompson WL, Ralay Ranaivo H, Behanna HA, Martin Watterson D: Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches. Int Rev Neurobiol 2007, 82:277-296.
• [26]Aloisi F: Immune function of microglia. Glia 2001, 36:165-179.
• [27]Purohit A, Ghilchik MW, Duncan L, Wang DY, Singh A, Walker MM, Reed MJ: Aromatase activity and interleukin-6 production by normal and malignant breast tissues. J Clin Endocrinol Metab 1995, 80:3052-3058.
• [28]Singh A, Purohit A, Duncan LJ, Mokbel K, Ghilchik MW, Reed MJ: Control of aromatase activity in breast tumours: the role of the immune system. J Steroid Biochem Mol Biol 1997, 61:185-192.
• [29]Reed MJ, Topping L, Coldham NG, Purohit A, Ghilchik MW, James VH: Control of aromatase activity in breast cancer cells: the role of cytokines and growth factors. J Steroid Biochem Mol Biol 1993, 44:589-596.
• [30]Purohit A, Ghilchik MW, Leese MP, Potter BV, Reed MJ: Regulation of aromatase activity by cytokines, PGE2 and 2-methoxyoestrone-3-O-sulphamate in fibroblasts derived from normal and malignant breast tissues. J Steroid Biochem Mol Biol 2005, 94:167-172.
• [31]Allan SM, Harrison DC, Read S, Collins B, Parsons AA, Philpott K, Rothwell NJ: Selective increases in cytokine expression in the rat brain in response to striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1. Brain Res Mol Brain Res 2001, 93:180-189.
• [32]Saldanha CJ, Tuerk MJ, Kim YH, Fernandes AO, Arnold AP, Schlinger BA: Distribution and regulation of telencephalic aromatase expression in the zebra finch revealed with a specific antibody. J Comp Neurol 2000, 423:619-630.
• [33]Rohmann KN, Schlinger BA, Saldanha CJ: Subcellular compartmentalization of aromatase is sexually dimorphic in the adult zebra finch brain. Dev Neurobiol 2007, 67:1-9.
• [34]Stokes TM, Leonard CM, Nottebohm F: The telencephalon, diencephalon, and mesencephalon of the canary, Serinus canaria, in stereotaxic coordinates. J Comp Neurol 1974, 156:337-374.
• [35]Saldanha CJ, Rohmann KN, Coomaralingam L, Wynne RD: Estrogen provision by reactive glia decreases apoptosis in the zebra finch (Taeniopygia guttata). J Neurobiol 2005, 64:192-201.
• [36]Saldanha CJ, Coomaralingam L: Overlap and co-expression of estrogen synthetic and responsive neurons in the songbird brain--a double-label immunocytochemical study. Gen Comp Endocrinol 2005, 141:66-75.
• [37]Streit WJ, Kreutzberg GW: Lectin binding by resting and reactive microglia. J Neurocytol 1987, 16:249-260.
• [38]Ayoub AE, Salm AK: Increased morphological diversity of microglia in the activated hypothalamic supraoptic nucleus. J Neurosci 2003, 23:7759-7766.
• [39]Roberts ML, Buchanan KL, Hasselquist D, Evans MR: Effects of testosterone and corticosterone on immunocompetence in the zebra finch. Horm Behav 2007, 51:126-134.
• [40]Wynne RD, Maas S, Saldanha CJ: Molecular characterization of the injury-induced aromatase transcript in the adult zebra finch brain. J Neurochem 2008, 105:1613-1624.
• [41]Peterson RS, Fernando G, Day L, Allen TA, Chapleau JD, Menjivar J, Schlinger BA, Lee DW: Aromatase expression and cell proliferation following injury of the adult zebra finch hippocampus. Dev Neurobiol 2007, 67:1867-1878.
• [42]Honma S, Shimodaira K, Shimizu Y, Tsuchiya N, Saito H, Yanaihara T, Okai T: The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells. Endocr J 2002, 49:371-377.
• [43]Morioka M, Shimodaira K, Kuwano Y, Fujikawa H, Saito H, Yanaihara T: Effect of interleukin-1beta on aromatase activity and cell proliferation in human osteoblast-like cells (HOS). Biochem Biophys Res Commun 2000, 268:60-64.
• [44]Purohit A, Newman SP, Reed MJ: The role of cytokines in regulating estrogen synthesis: implications for the etiology of breast cancer. Breast Cancer Res 2002, 4:65-69.
• [45]Veerapaneni P, Kirma N, Nair HB, Hammes LS, Hall KL, Tekmal RR: Elevated aromatase expression correlates with cervical carcinoma progression. Gynecol Oncol 2009, 114:496-500.
• [46]Cerciat M, Unkila M, Garcia-Segura LM, Arevalo MA: Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-gamma-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro. Glia 2010, 58:93-102.
• [47]Dodel RC, Du Y, Bales KR, Gao F, Paul SM: Sodium salicylate and 17beta-estradiol attenuate nuclear transcription factor NF-kappaB translocation in cultured rat astroglial cultures following exposure to amyloid A beta(1-40) and lipopolysaccharides. J Neurochem 1999, 73:1453-1460.
• [48]Tapia-Gonzalez S, Carrero P, Pernia O, Garcia-Segura LM, Diz-Chaves Y: Selective oestrogen receptor (ER) modulators reduce microglia reactivity in vivo after peripheral inflammation: potential role of microglial ERs. J Endocrinol 2008, 198:219-230.
• [49]Dhandapani KM, Brann DW: Protective effects of estrogen and selective estrogen receptor modulators in the brain. Biol Reprod 2002, 67:1379-1385.
• [50]Garcia-Ovejero D, Veiga S, Garcia-Segura LM, Doncarlos LL: Glial expression of estrogen and androgen receptors after rat brain injury. J Comp Neurol 2002, 450:256-271.
• [51]Morissette M, Le Saux M, D'Astous M, Jourdain S, Al Sweidi S, Morin N, Estrada-Camarena E, Mendez P, Garcia-Segura LM, Di Paolo T: Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain. J Steroid Biochem Mol Biol 2008, 108:327-338.
• [52]Dubal DB, Wise PM: Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology 2001, 142:43-48.
• [53]Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM: Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J Neurosci 1999, 19:6385-6393.
• [54]Denes A, Thornton P, Rothwell NJ, Allan SM: Inflammation and brain injury: Acute cerebral ischaemia, peripheral and central inflammation. Brain Behav Immun 2009.
• [55]Laird MD, Vender JR, Dhandapani KM: Opposing roles for reactive astrocytes following traumatic brain injury. Neurosignals 2008, 16:154-164.
• [56]Allan SM: The role of pro- and antiinflammatory cytokines in neurodegeneration. Ann N Y Acad Sci 2000, 917:84-93.
• [57]Swartz KR, Liu F, Sewell D, Schochet T, Campbell I, Sandor M, Fabry Z: Interleukin-6 promotes post-traumatic healing in the central nervous system. Brain Res 2001, 896:86-95.
• [58]Penkowa M, Giralt M, Lago N, Camats J, Carrasco J, Hernandez J, Molinero A, Campbell IL, Hidalgo J: Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury. Exp Neurol 2003, 181:130-148.
• [59]Quintana A, Giralt M, Molinero A, Campbell IL, Penkowa M, Hidalgo J: Analysis of the cerebral transcriptome in mice subjected to traumatic brain injury: importance of IL-6. Neuroimmunomodulation 2007, 14:139-143.
• [60]Acarin L, Gonzalez B, Castellano B: Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain. Eur J Neurosci 2000, 12:3505-3520.
• [61]Gadient RA, Cron KC, Otten U: Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes. Neurosci Lett 1990, 117:335-340.
• [62]Chao CC, Hu S, Ehrlich L, Peterson PK: Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain Behav Immun 1995, 9:355-365.
• [63]Pearson VL, Rothwell NJ, Toulmond S: Excitotoxic brain damage in the rat induces interleukin-1beta protein in microglia and astrocytes: correlation with the progression of cell death. Glia 1999, 25:311-323.