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Licensed Unlicensed Requires Authentication Published by De Gruyter February 22, 2014

Possible roles of astrocytes in estrogen neuroprotection during cerebral ischemia

  • Cuifen Wang

    Cuifen Wang is taking her post-doc research at School of Pharmacy, Marshall University, West Virginia, USA. She is skilled in neural degenerative diseases with immunohistochemistry and fluorescence microscopy in brain tissues and employs a variety of biochemical and molecular biological techniques to develop new chemicals against cerebral diseases.

    , Chao Jie

    Jie Chao is a professor at Department of Physiology at the Medical School of Southeast University, Nanjing, China. He got his PhD from University of Kansas Medical Center. He has ample experience with the technique of intravital microscopy, as well as molecular biologic techniques in neuroscience and respiration physiology. He is first-author or correspond-author of more than 20 peer-reviewed papers of his field. The primary objective of Jie’s laboratory is to explore, in vivo and in vitro, molecular and cellular mechanisms underlying the inflammation of silicosis.

    and Xiaoniu Dai

    Xiaoniu Dai is a lecture at the Department of Physiology at the Medical School of Southeast University, Nanjing, China. He got his PhD from the Medical School of Nagoya University, Japan. His research interest is primarily in learning-memory mechanisms with focus on the effects of neurosteroids on synaptic transmission and synaptic plasticity by using electrophysiological techniques, including whole cell patch clamping and field excitatory postsynaptic potentials (fEPSPs) recording from brain slice.

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Abstract

17β-Estradiol (E2), one of female sex hormones, has well-documented neuroprotective effects in a variety of clinical and experimental disorders of the central cerebral ischemia, including stroke and neurodegenerative diseases. The cellular mechanisms that underlie these protective effects of E2 are uncertain because a number of different cell types express estrogen receptors in the central nervous system. Astrocytes are the most abundant cells in the central nervous system and provide structural and nutritive support of neurons. They interact with neurons by cross-talk, both physiologically and pathologically. Proper astrocyte function is particularly important for neuronal survival under ischemic conditions. Dysfunction of astrocytes resulting from ischemia significantly influences the responses of other brain cells to injury. Recent studies demonstrate that estrogen receptors are expressed in astrocytes, indicating that E2 may exert multiple regulatory actions on astrocytes. Cerebral ischemia induced changes in the expression of estrogen receptors in astrocytes. In the present review, we summarize the data in support of possible roles for astrocytes in the mediation of neuroprotection by E2 against cerebral ischemia.


Corresponding author: Xiaoniu Dai, Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu Province, China, e-mail:

About the authors

Cuifen Wang

Cuifen Wang is taking her post-doc research at School of Pharmacy, Marshall University, West Virginia, USA. She is skilled in neural degenerative diseases with immunohistochemistry and fluorescence microscopy in brain tissues and employs a variety of biochemical and molecular biological techniques to develop new chemicals against cerebral diseases.

Chao Jie

Jie Chao is a professor at Department of Physiology at the Medical School of Southeast University, Nanjing, China. He got his PhD from University of Kansas Medical Center. He has ample experience with the technique of intravital microscopy, as well as molecular biologic techniques in neuroscience and respiration physiology. He is first-author or correspond-author of more than 20 peer-reviewed papers of his field. The primary objective of Jie’s laboratory is to explore, in vivo and in vitro, molecular and cellular mechanisms underlying the inflammation of silicosis.

Xiaoniu Dai

Xiaoniu Dai is a lecture at the Department of Physiology at the Medical School of Southeast University, Nanjing, China. He got his PhD from the Medical School of Nagoya University, Japan. His research interest is primarily in learning-memory mechanisms with focus on the effects of neurosteroids on synaptic transmission and synaptic plasticity by using electrophysiological techniques, including whole cell patch clamping and field excitatory postsynaptic potentials (fEPSPs) recording from brain slice.

Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (30770573), the 973 program from the Minister of Science and Technology in China (2007CB512304), and the SRF for ROCS, SEM (2008-101).

References

Acs, P., Kipp, M., Norkute, A., Johann, S., Clarner, T., Braun, A., Berente, Z., Komoly, S., and Beyer, C. (2009). 17β-estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice. Glia 57, 807–814.10.1002/glia.20806Search in Google Scholar PubMed

Al-Bader, M.D., Malatiali, S.A., and Redzic, Z.B. (2011). Expression of estrogen receptor α and β in rat astrocytes in primary culture: effects of hypoxia and glucose deprivation. Physiol. Res. 60, 951–960.10.33549/physiolres.932167Search in Google Scholar PubMed

Albanito, L., Madeo, A., Lappano, R., Vivacqua, A., Rago, V., Carpino, A., Oprea, T.I., Prossnitz, E.R., Musti, A.M., Ando, S., et al. (2007). G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17β-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells. Cancer Res. 67, 1859–1866.10.1158/0008-5472.CAN-06-2909Search in Google Scholar PubMed

Alkayed, N.J., Harukuni, I., Kimes, A.S., London, E.D., Traystman, R.J., and Hurn, P.D. (1998). Gender-linked brain injury in experimental stroke. Stroke 29, 159–165; discussion 166.10.1161/01.STR.29.1.159Search in Google Scholar

Alkayed, N.J., Murphy, S.J., Traystman, R.J., Hurn, P.D., and Miller, V.M. (2000). Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke 31, 161–168.10.1161/01.STR.31.1.161Search in Google Scholar

Al Sweidi, S., Sanchez, M.G., Bourque, M., Morissette, M., Dluzen, D., and Di Paolo, T. (2012). Oestrogen receptors and signalling pathways: implications for neuroprotective effects of sex steroids in Parkinson’s disease. J. Neuroendocrinol. 24, 48–61.10.1111/j.1365-2826.2011.02193.xSearch in Google Scholar PubMed

Araujo, G.W., Beyer, C., and Arnold, S. (2008). Oestrogen influences on mitochondrial gene expression and respiratory chain activity in cortical and mesencephalic astrocytes. J. Neuroendocrinol. 20, 930–941.10.1111/j.1365-2826.2008.01747.xSearch in Google Scholar PubMed

Arevalo, M.A., Santos-Galindo, M., Bellini, M.J., Azcoitia, I., and Garcia-Segura, L.M. (2010). Actions of estrogens on glial cells: implications for neuroprotection. Biochim. Biophys. Acta 1800, 1106–1112.10.1016/j.bbagen.2009.10.002Search in Google Scholar PubMed

Arimoto, J.M., Wong, A., Rozovsky, I., Lin, S.W., Morgan, T.E., and Finch, C.E. (2013). Age increase of estrogen receptor-α (ERα) in cortical astrocytes impairs neurotrophic support in male and female rats. Endocrinology 154, 2101–2113.10.1210/en.2012-2046Search in Google Scholar PubMed PubMed Central

Arnold, S., de Araujo, G.W., and Beyer, C. (2008). Gender-specific regulation of mitochondrial fusion and fission gene transcription and viability of cortical astrocytes by steroid hormones. J. Mol. Endocrinol. 41, 289–300.10.1677/JME-08-0085Search in Google Scholar PubMed

Attwell, D., Buchan, A.M., Charpak, S., Lauritzen, M., Macvicar, B.A., and Newman, E.A. (2010). Glial and neuronal control of brain blood flow. Nature 468, 232–243.10.1038/nature09613Search in Google Scholar

Ayus, J.C., Achinger, S.G., and Arieff, A. (2008). Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. Am. J. Physiol. Renal. Physiol. 295, F619–F624.10.1152/ajprenal.00502.2007Search in Google Scholar

Azcoitia, I., Sierra, A., and Garcia-Segura, L.M. (1999). Localization of estrogen receptor β-immunoreactivity in astrocytes of the adult rat brain. Glia 26, 260–267.10.1002/(SICI)1098-1136(199905)26:3<260::AID-GLIA7>3.0.CO;2-RSearch in Google Scholar

Azcoitia, I., Santos-Galindo, M., Arevalo, M.A., and Garcia-Segura, L.M. (2010). Role of astroglia in the neuroplastic and neuroprotective actions of estradiol. Eur. J. Neurosci. 32, 1995–2002.10.1111/j.1460-9568.2010.07516.xSearch in Google Scholar

Barreto, G., Veiga, S., Azcoitia, I., Garcia-Segura, L.M., and Garcia-Ovejero, D. (2007). Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone. Eur. J. Neurosci. 25, 3039–3046.10.1111/j.1460-9568.2007.05563.xSearch in Google Scholar

Barreto, G., Santos-Galindo, M., Diz-Chaves, Y., Pernia, O., Carrero, P., Azcoitia, I., and Garcia-Segura, L.M. (2009). Selective estrogen receptor modulators decrease reactive astrogliosis in the injured brain: effects of aging and prolonged depletion of ovarian hormones. Endocrinology 150, 5010–5015.10.1210/en.2009-0352Search in Google Scholar

Boada, M., Antunez, C., Lopez-Arrieta, J., Caruz, A., Moreno-Rey, C., Ramirez-Lorca, R., Moron, F. J., Hernandez, I., Mauleon, A., Rosende-Roca, M., et al. (2012). Estrogen receptor α gene variants are associated with Alzheimer’s disease. Neurobiol. Aging 33, 198. e115–198.e124.10.1016/j.neurobiolaging.2010.06.016Search in Google Scholar

Boix, R., del Barrio, J.L., Saz, P., Rene, R., Manubens, J.M., Lobo, A., Gascon, J., de Arce, A., Diaz-Guzman, J., Bergareche, A., et al. (2006). Stroke prevalence among the Spanish elderly: an analysis based on screening surveys. BMC Neurol. 6, 36.10.1186/1471-2377-6-36Search in Google Scholar

Bologa, C.G., Revankar, C.M., Young, S.M., Edwards, B.S., Arterburn, J.B., Kiselyov, A.S., Parker, M.A., Tkachenko, S.E., Savchuck, N.P., Sklar, L.A., et al. (2006). Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat. Chem. Biol. 2, 207–212.10.1038/nchembio775Search in Google Scholar

Bondar, G., Kuo, J., Hamid, N., and Micevych, P. (2009). Estradiol-induced estrogen receptor – a trafficking. J. Neurosci. 29, 15323–15330.10.1523/JNEUROSCI.2107-09.2009Search in Google Scholar

Bourque, M., Dluzen, D.E., and Di Paolo, T. (2012). Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson’s disease. Front. Neuroendocrinol. 33, 169–178.10.1016/j.yfrne.2012.02.003Search in Google Scholar PubMed

Brailoiu, E., Dun, S.L., Brailoiu, G.C., Mizuo, K., Sklar, L.A., Oprea, T.I., Prossnitz, E.R., and Dun, N.J. (2007). Distribution and characterization of estrogen receptor G protein-coupled receptor 30 in the rat central nervous system. J. Endocrinol. 193, 311–321.10.1677/JOE-07-0017Search in Google Scholar PubMed

Brann, D.W., Dhandapani, K., Wakade, C., Mahesh, V.B., and Khan, M.M. (2007). Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 72, 381–405.10.1016/j.steroids.2007.02.003Search in Google Scholar PubMed PubMed Central

Brann, D., Raz, L., Wang, R., Vadlamudi, R., and Zhang, Q. (2012). Oestrogen signalling and neuroprotection in cerebral ischaemia. J. Neuroendocrinol. 24, 34–47.10.1111/j.1365-2826.2011.02185.xSearch in Google Scholar PubMed PubMed Central

Brinton, R.D. (2008). The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trends Neurosci. 31, 529–537.10.1016/j.tins.2008.07.003Search in Google Scholar PubMed

Brown, C.M., Suzuki, S., Jelks, K.A., and Wise, P.M. (2009). Estradiol is a potent protective, restorative, and trophic factor after brain injury. Semin. Reprod. Med. 27, 240–249.10.1055/s-0029-1216277Search in Google Scholar PubMed PubMed Central

Cambiasso, M.J., Colombo, J.A., and Carrer, H.F. (2000). Differential effect of oestradiol and astroglia-conditioned media on the growth of hypothalamic neurons from male and female rat brains. Eur. J. Neurosci. 12, 2291–2298.10.1046/j.1460-9568.2000.00120.xSearch in Google Scholar PubMed

Carlstrom, L., Ke, Z.J., Unnerstall, J.R., Cohen, R.S., and Pandey, S.C. (2001). Estrogen modulation of the cyclic AMP response element-binding protein pathway. Effects of long-term and acute treatments. Neuroendocrinology 74, 227–243.10.1159/000054690Search in Google Scholar PubMed

Carswell, H.V., Macrae, I.M., Gallagher, L., Harrop, E., and Horsburgh, K.J. (2004). Neuroprotection by a selective estrogen receptor β agonist in a mouse model of global ischemia. Am. J. Physiol. Heart Circ. Physiol. 287, H1501–H1504.10.1152/ajpheart.00227.2004Search in Google Scholar PubMed

Carswell, H.V., Dominiczak, A.F., Garcia-Segura, L.M., Harada, N., Hutchison, J.B., and Macrae, I.M. (2005). Brain aromatase expression after experimental stroke: topography and time course. J. Steroid Biochem. Mol. Biol. 96, 89–91.10.1016/j.jsbmb.2005.02.016Search in Google Scholar PubMed

Cerciat, M., Unkila, M., Garcia-Segura, L.M., and Arevalo, M.A. (2010). Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-γ-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro. Glia 58, 93–102.10.1002/glia.20904Search in Google Scholar PubMed

Chaban, V.V., Lakhter, A.J., and Micevych, P. (2004). A membrane estrogen receptor mediates intracellular calcium release in astrocytes. Endocrinology 145, 3788–3795.10.1210/en.2004-0149Search in Google Scholar PubMed

Cheong, R.Y., Kwakowsky, A., Barad, Z., Porteous, R., Herbison, A.E., and Abraham, I.M. (2012). Estradiol acts directly and indirectly on multiple signaling pathways to phosphorylate cAMP-response element binding protein in GnRH neurons. Endocrinology 153, 3792–3803.10.1210/en.2012-1232Search in Google Scholar PubMed

Cho, J., Kim, D., Lee, S., and Lee, Y. (2005). Cobalt chloride-induced estrogen receptor α down-regulation involves hypoxia-inducible factor-1α in MCF-7 human breast cancer cells. Mol. Endocrinol. 19, 1191–1199.10.1210/me.2004-0162Search in Google Scholar PubMed

Christian, C.A., Glidewell-Kenney, C., Jameson, J.L., and Moenter, S.M. (2008). Classical estrogen receptor α signaling mediates negative and positive feedback on gonadotropin-releasing hormone neuron firing. Endocrinology 149, 5328–5334.10.1210/en.2008-0520Search in Google Scholar PubMed PubMed Central

Cimarosti, H., Jones, N.M., O’Shea, R.D., Pow, D.V., Salbego, C., and Beart, P.M. (2005). Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor α. Neurosci. Lett. 385, 52–57.10.1016/j.neulet.2005.05.006Search in Google Scholar PubMed

Coleman, K.M., Dutertre, M., El-Gharbawy, A., Rowan, B.G., Weigel, N.L., and Smith, C.L. (2003). Mechanistic differences in the activation of estrogen receptor-α (ER α)- and ER β-dependent gene expression by cAMP signaling pathway(s). J. Biol. Chem. 278, 12834–12845.10.1074/jbc.M212312200Search in Google Scholar PubMed

Cordeau, P. Jr., Lalancette-Hebert, M., Weng, Y.C., and Kriz, J. (2008). Live imaging of neuroinflammation reveals sex and estrogen effects on astrocyte response to ischemic injury. Stroke 39, 935–942.10.1161/STROKEAHA.107.501460Search in Google Scholar PubMed

Dai, X., Chen, L., and Sokabe, M. (2007). Neurosteroid estradiol rescues ischemia-induced deficit in the long-term potentiation of rat hippocampal CA1 neurons. Neuropharmacology 52, 1124–1138.10.1016/j.neuropharm.2006.11.012Search in Google Scholar PubMed

Dallas, M., Boycott, H.E., Atkinson, L., Miller, A., Boyle, J.P., Pearson, H.A., and Peers, C. (2007). Hypoxia suppresses glutamate transport in astrocytes. J. Neurosci. 27, 3946–3955.10.1523/JNEUROSCI.5030-06.2007Search in Google Scholar PubMed PubMed Central

De Butte-Smith, M., Gulinello, M., Zukin, R.S., and Etgen, A.M. (2009). Chronic estradiol treatment increases CA1 cell survival but does not improve visual or spatial recognition memory after global ischemia in middle-aged female rats. Horm. Behav. 55, 442–453.10.1016/j.yhbeh.2008.11.011Search in Google Scholar PubMed PubMed Central

Devarajan, A., Bourquard, N., Hama, S., Navab, M., Grijalva, V.R., Morvardi, S., Clarke, C.F., Vergnes, L., Reue, K., Teiber, J.F., et al. (2011). Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. Antioxid. Redox Signal 14, 341–351.10.1089/ars.2010.3430Search in Google Scholar PubMed PubMed Central

Dhandapani, K.M., Wade, F.M., Mahesh, V.B., and Brann, D.W. (2005). Astrocyte-derived transforming growth factor-β mediates the neuroprotective effects of 17β-estradiol: involvement of nonclassical genomic signaling pathways. Endocrinology 146, 2749–2759.10.1210/en.2005-0014Search in Google Scholar PubMed

Dodel, R.C., Du, Y., Bales, K.R., Gao, F., and Paul, S.M. (1999). Sodium salicylate and 17β-estradiol attenuate nuclear transcription factor NF-κB translocation in cultured rat astroglial cultures following exposure to amyloid Aβ(1-40) and lipopolysaccharides. J. Neurochem. 73, 1453–1460.10.1046/j.1471-4159.1999.0731453.xSearch in Google Scholar PubMed

Donzelli, A., Braida, D., Finardi, A., Capurro, V., Valsecchi, A.E., Colleoni, M., and Sala, M. (2010). Neuroprotective effects of genistein in Mongolian gerbils: estrogen receptor-β involvement. J. Pharmacol. Sci. 114, 158–167.10.1254/jphs.10164FPSearch in Google Scholar PubMed

Dubal, D.B. and Wise, P.M. (2002). Estrogen and neuroprotection: from clinical observations to molecular mechanisms. Dialogues Clin. Neurosci. 4, 149–161.10.31887/DCNS.2002.4.2/ddubalSearch in Google Scholar

Dubal, D.B., Zhu, H., Yu, J., Rau, S.W., Shughrue, P.J., Merchenthaler, I., Kindy, M.S., and Wise, P.M. (2001). Estrogen receptor α, not β, is a critical link in estradiol-mediated protection against brain injury. Proc. Natl. Acad. Sci. USA 98, 1952–1957.10.1073/pnas.98.4.1952Search in Google Scholar PubMed PubMed Central

Dubal, D.B., Rau, S.W., Shughrue, P.J., Zhu, H., Yu, J., Cashion, A.B., Suzuki, S., Gerhold, L.M., Bottner, M.B., Dubal, S.B., et al. (2006). Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERα in estradiol-mediated protection against delayed cell death. Endocrinology 147, 3076–3084.10.1210/en.2005-1177Search in Google Scholar PubMed

Dugan, L.L. and Kim-Han, J.S. (2004). Astrocyte mitochondria in in vitro models of ischemia. J. Bioenerg. Biomembr. 36, 317–321.10.1023/B:JOBB.0000041761.61554.44Search in Google Scholar

Eichner, L.J. and Giguere, V. (2011). Estrogen related receptors (ERRs): a new dawn in transcriptional control of mitochondrial gene networks. Mitochondrion 11, 544–552.10.1016/j.mito.2011.03.121Search in Google Scholar PubMed

Elzer, J.G., Muhammad, S., Wintermantel, T.M., Regnier- Vigouroux, A., Ludwig, J., Schutz, G., and Schwaninger, M. (2010). Neuronal estrogen receptor-α mediates neuroprotection by 17β-estradiol. J. Cereb. Blood Flow Metab. 30, 935–942.10.1038/jcbfm.2009.258Search in Google Scholar PubMed PubMed Central

Falkeborn, M., Persson, I., Terent, A., Adami, H.O., Lithell, H., and Bergstrom, R. (1993). Hormone replacement therapy and the risk of stroke. Follow-up of a population-based cohort in Sweden. Arch. Intern. Med. 153, 1201–1209.10.1001/archinte.1993.00410100035005Search in Google Scholar

Filardo, E.J., Quinn, J.A., Bland, K.I., and Frackelton, A.R. Jr. (2000). Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol. Endocrinol. 14, 1649–1660.10.1210/mend.14.10.0532Search in Google Scholar PubMed

Fuente-Martin, E., Garcia-Caceres, C., Morselli, E., Clegg, D.J., Chowen, J.A., Finan, B., Brinton, R.D., and Tschop, M.H. (2013). Estrogen, astrocytes and the neuroendocrine control of metabolism. Rev. Endocr. Metab. Disord. 14, 331–338.10.1007/s11154-013-9263-7Search in Google Scholar PubMed PubMed Central

Funakoshi, T., Yanai, A., Shinoda, K., Kawano, M.M., and Mizukami, Y. (2006). G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochem. Biophys. Res. Commun. 346, 904–910.10.1016/j.bbrc.2006.05.191Search in Google Scholar PubMed

Galbiati, M., Martini, L., and Melcangi, R.C. (2002). Oestrogens, via transforming growth factor α, modulate basic fibroblast growth factor synthesis in hypothalamic astrocytes: in vitro observations. J. Neuroendocrinol. 14, 829–835.10.1046/j.1365-2826.2002.00852.xSearch in Google Scholar PubMed

Garcia-Ovejero, D., Veiga, S., Garcia-Segura, L.M., and Doncarlos, L.L. (2002). Glial expression of estrogen and androgen receptors after rat brain injury. J. Comp. Neurol. 450, 256–271.10.1002/cne.10325Search in Google Scholar PubMed

Garcia-Ovejero, D., Azcoitia, I., Doncarlos, L.L., Melcangi, R.C., and Garcia-Segura, L.M. (2005). Glia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones. Brain Res. Brain Res. Rev. 48, 273–286.10.1016/j.brainresrev.2004.12.018Search in Google Scholar PubMed

Garcia-Segura, L.M. and McCarthy, M.M. (2004). Minireview: role of glia in neuroendocrine function. Endocrinology 145, 1082–1086.10.1210/en.2003-1383Search in Google Scholar PubMed

Garcia-Segura, L.M., Luquin, S., Parducz, A., and Naftolin, F. (1994). Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus. Glia 10, 59–69.10.1002/glia.440100108Search in Google Scholar PubMed

Gingerich, S., Kim, G.L., Chalmers, J.A., Koletar, M.M., Wang, X., Wang, Y., and Belsham, D.D. (2010). Estrogen receptor α and G-protein coupled receptor 30 mediate the neuroprotective effects of 17β-estradiol in novel murine hippocampal cell models. Neuroscience 170, 54–66.10.1016/j.neuroscience.2010.06.076Search in Google Scholar PubMed

Giordano, G., Cole, T.B., Furlong, C.E., and Costa, L.G. (2011). Paraoxonase 2 (PON2) in the mouse central nervous system: a neuroprotective role? Toxicol. Appl. Pharmacol. 256, 369–378.10.1016/j.taap.2011.02.014Search in Google Scholar PubMed PubMed Central

Giordano, G., Tait, L., Furlong, C.E., Cole, T.B., Kavanagh, T.J., and Costa, L.G. (2013). Gender differences in brain susceptibility to oxidative stress are mediated by levels of paraoxonase-2 expression. Free Radic. Biol. Med. 58, 98–108.10.1016/j.freeradbiomed.2013.01.019Search in Google Scholar PubMed PubMed Central

Giraud, S.N., Caron, C.M., Pham-Dinh, D., Kitabgi, P., and Nicot, A.B. (2010). Estradiol inhibits ongoing autoimmune neuroinflammation and NFκB-dependent CCL2 expression in reactive astrocytes. Proc. Natl. Acad. Sci. USA 107, 8416–8421.10.1073/pnas.0910627107Search in Google Scholar PubMed PubMed Central

Gould, E., Woolley, C.S., Frankfurt, M., and McEwen, B.S. (1990). Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J. Neurosci. 10, 1286–1291.10.1523/JNEUROSCI.10-04-01286.1990Search in Google Scholar

Guevara, R., Gianotti, M., Oliver, J., and Roca, P. (2011). Age and sex-related changes in rat brain mitochondrial oxidative status. Exp. Gerontol. 46, 923–928.10.1016/j.exger.2011.08.003Search in Google Scholar PubMed

Gulinello, M., Lebesgue, D., Jover-Mengual, T., Zukin, R.S., and Etgen, A.M. (2006). Acute and chronic estradiol treatments reduce memory deficits induced by transient global ischemia in female rats. Horm. Behav. 49, 246–260.10.1016/j.yhbeh.2005.07.010Search in Google Scholar PubMed PubMed Central

Guo, J., Duckles, S.P., Weiss, J.H., Li, X., and Krause, D.N. (2012). 17β-Estradiol prevents cell death and mitochondrial dysfunction by an estrogen receptor-dependent mechanism in astrocytes after oxygen-glucose deprivation/reperfusion. Free Radic. Biol. Med. 52, 2151–2160.10.1016/j.freeradbiomed.2012.03.005Search in Google Scholar PubMed PubMed Central

Hall, E.D., Pazara, K.E., and Linseman, K.L. (1991). Sex differences in postischemic neuronal necrosis in gerbils. J. Cereb. Blood Flow Metab. 11, 292–298.10.1038/jcbfm.1991.61Search in Google Scholar PubMed

Huppmann, S., Romer, S., Altmann, R., Obladen, M., and Berns, M. (2008). 17β-estradiol attenuates hyperoxia-induced apoptosis in mouse C8-D1A cell line. J. Neurosci. Res. 86, 3420–3426.10.1002/jnr.21777Search in Google Scholar PubMed

Iadecola, C. and Nedergaard, M. (2007). Glial regulation of the cerebral microvasculature. Nat. Neurosci. 10, 1369–1376.10.1038/nn2003Search in Google Scholar

Inagaki, T., Kaneko, N., Zukin, R.S., Castillo, P.E., and Etgen, A.M. (2012). Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats. PLoS One 7, e38018.10.1371/journal.pone.0038018Search in Google Scholar

Ivanova, T., Karolczak, M., and Beyer, C. (2001). Estrogen stimulates the mitogen-activated protein kinase pathway in midbrain astroglia. Brain Res. 889, 264–269.10.1016/S0006-8993(00)03149-8Search in Google Scholar

Ji, Y., Tang, B., and Traub, R.J. (2011). Spinal estrogen receptor α mediates estradiol-induced pronociception in a visceral pain model in the rat. Pain 152, 1182–1191.10.1016/j.pain.2011.01.046Search in Google Scholar PubMed PubMed Central

Johann, S. and Beyer, C. (2013). Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia J. Steroid Biochem. Mol. Biol. 137, 71–81.10.1016/j.jsbmb.2012.11.006Search in Google Scholar PubMed

Johann, S., Dahm, M., Kipp, M., Beyer, C., and Arnold, S. (2010). Oestrogen regulates mitochondrial respiratory chain enzyme transcription in the mouse spinal cord. J. Neuroendocrinol. 22, 926–935.10.1111/j.1365-2826.2010.02006.xSearch in Google Scholar PubMed

Jover-Mengual, T., Zukin, R.S., and Etgen, A.M. (2007). MAPK signaling is critical to estradiol protection of CA1 neurons in global ischemia. Endocrinology 148, 1131–1143.10.1210/en.2006-1137Search in Google Scholar PubMed PubMed Central

Kalaitzidis, D. and Gilmore, T.D. (2005). Transcription factor cross-talk: the estrogen receptor and NF-kappaB. Trends Endocrinol. Metab. 16, 46–52.10.1016/j.tem.2005.01.004Search in Google Scholar PubMed

Kanda, N. and Watanabe, S. (2003a). 17β-estradiol inhibits MCP-1 production in human keratinocytes. J. Invest. Dermatol. 120, 1058–1066.10.1046/j.1523-1747.2003.12255.xSearch in Google Scholar PubMed

Kanda, N. and Watanabe, S. (2003b). 17 β-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by promoting Bcl-2 expression. J. Invest. Dermatol. 121, 1500–1509.10.1111/j.1523-1747.2003.12617.xSearch in Google Scholar PubMed

Kipp, M., Karakaya, S., Johann, S., Kampmann, E., Mey, J., and Beyer, C. (2007). Oestrogen and progesterone reduce lipopolysaccharide-induced expression of tumour necrosis factor-α and interleukin-18 in midbrain astrocytes. J. Neuroendocrinol. 19, 819–822.10.1111/j.1365-2826.2007.01588.xSearch in Google Scholar PubMed

Kuo, J., Hamid, N., Bondar, G., Prossnitz, E.R., and Micevych, P. (2010). Membrane estrogen receptors stimulate intracellular calcium release and progesterone synthesis in hypothalamic astrocytes. J. Neurosci. 30, 12950–12957.10.1523/JNEUROSCI.1158-10.2010Search in Google Scholar PubMed PubMed Central

Kuppers, E., Ivanova, T., Karolczak, M., Lazarov, N., Fohr, K., and Beyer, C. (2001). Classical and nonclassical estrogen action in the developing midbrain. Horm. Behav. 40, 196–202.10.1006/hbeh.2001.1671Search in Google Scholar PubMed

Kwakowsky, A., Cheong, R.Y., Herbison, A.E., and Abraham, I.M. (2013). Non-classical effects of estradiol on cAMP responsive element binding protein phosphorylation in gonadotropin-releasing hormone neurons: mechanisms and role. Front. Neuroendocrinol.Search in Google Scholar

Lang, J.T. and McCullough, L.D. (2008). Pathways to ischemic neuronal cell death: are sex differences relevant? J. Transl. Med. 6, 33.10.1186/1479-5876-6-33Search in Google Scholar PubMed PubMed Central

Lebesgue, D., Chevaleyre, V., Zukin, R.S., and Etgen, A.M. (2009). Estradiol rescues neurons from global ischemia-induced cell death: multiple cellular pathways of neuroprotection. Steroids 74, 555–561.10.1016/j.steroids.2009.01.003Search in Google Scholar PubMed PubMed Central

Lebesgue, D., Traub, M., De Butte-Smith, M., Chen, C., Zukin, R.S., Kelly, M.J., and Etgen, A.M. (2010). Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats. PLoS One 5, e8642.10.1371/journal.pone.0008642Search in Google Scholar PubMed PubMed Central

Lee, E.S., Sidoryk, M., Jiang, H., Yin, Z., and Aschner, M. (2009). Estrogen and tamoxifen reverse manganese-induced glutamate transporter impairment in astrocytes. J. Neurochem. 110, 530–544.10.1111/j.1471-4159.2009.06105.xSearch in Google Scholar PubMed PubMed Central

Lee, E., Sidoryk-Wegrzynowicz, M., Wang, N., Webb, A., Son, D.S., Lee, K., and Aschner, M. (2012). GPR30 regulates glutamate transporter GLT-1 expression in rat primary astrocytes. J. Biol. Chem. 287, 26817–26828.10.1074/jbc.M112.341867Search in Google Scholar PubMed PubMed Central

Lewis, D.K., Johnson, A.B., Stohlgren, S., Harms, A., and Sohrabji, F. (2008). Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats. J. Neuroimmunol. 195, 47–59.10.1016/j.jneuroim.2008.01.006Search in Google Scholar PubMed PubMed Central

Liu, M., Hurn, P.D., Roselli, C.E., and Alkayed, N.J. (2007). Role of P450 aromatase in sex-specific astrocytic cell death. J. Cereb. Blood Flow Metab. 27, 135–141.10.1038/sj.jcbfm.9600331Search in Google Scholar PubMed

Loram, L.C., Sholar, P.W., Taylor, F.R., Wiesler, J.L., Babb, J.A., Strand, K.A., Berkelhammer, D., Day, H.E., Maier, S.F., and Watkins, L.R. (2012). Sex and estradiol influence glial pro-inflammatory responses to lipopolysaccharide in rats. Psychoneuroendocrinology 37, 1688–1699.10.1016/j.psyneuen.2012.02.018Search in Google Scholar PubMed PubMed Central

Lu, A., Ran, R.Q., Clark, J., Reilly, M., Nee, A., and Sharp, F.R. (2002). 17-β-estradiol induces heat shock proteins in brain arteries and potentiates ischemic heat shock protein induction in glia and neurons. J. Cereb. Blood Flow Metab. 22, 183–195.10.1097/00004647-200202000-00006Search in Google Scholar PubMed

Martinez, L. and de Lacalle, S. (2007). Astrocytic reaction to a lesion, under hormonal deprivation. Neurosci. Lett. 415, 190–193.10.1016/j.neulet.2007.01.020Search in Google Scholar PubMed PubMed Central

Mateos, L., Persson, T., Katoozi, S., Gil-Bea, F.J., and Cedazo-Minguez, A. (2012). Estrogen protects against amyloid-β toxicity by estrogen receptor α-mediated inhibition of Daxx translocation. Neurosci. Lett. 506, 245–250.10.1016/j.neulet.2011.11.016Search in Google Scholar PubMed

Matsuda, K., Sakamoto, H., Mori, H., Hosokawa, K., Kawamura, A., Itose, M., Nishi, M., Prossnitz, E.R., and Kawata, M. (2008). Expression and intracellular distribution of the G protein-coupled receptor 30 in rat hippocampal formation. Neurosci. Lett. 441, 94–99.10.1016/j.neulet.2008.05.108Search in Google Scholar PubMed

McAsey, M.E., Cady, C., Jackson, L.M., Li, M., Randall, S., Nathan, B.P., and Struble, R.G. (2006). Time course of response to estradiol replacement in ovariectomized mice: brain apolipoprotein E and synaptophysin transiently increase and glial fibrillary acidic protein is suppressed. Exp. Neurol. 197, 197–205.10.1016/j.expneurol.2005.09.008Search in Google Scholar PubMed

McCarthy, J.B., Barker-Gibb, A.L., Alves, S.E., and Milner, T.A. (2002). TrkA immunoreactive astrocytes in dendritic fields of the hippocampal formation across estrous. Glia 38, 36–44.10.1002/glia.10060Search in Google Scholar PubMed

McCullough, L.D., Blizzard, K., Simpson, E.R., Oz, O.K., and Hurn, P.D. (2003). Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J. Neurosci. 23, 8701–8705.10.1523/JNEUROSCI.23-25-08701.2003Search in Google Scholar

McCullough, L.D., Zeng, Z., Blizzard, K.K., Debchoudhury, I., and Hurn, P.D. (2005). Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection. J. Cereb. Blood Flow Metab. 25, 502–512.10.1038/sj.jcbfm.9600059Search in Google Scholar PubMed

McEwen, B. (2000). Neuronal and cognitive effects of oestrogens. Introduction. Novartis Found. Symp. 230, 1–6.Search in Google Scholar

McEwen, B., Akama, K., Alves, S., Brake, W.G., Bulloch, K., Lee, S., Li, C., Yuen, G., and Milner, T.A. (2001). Tracking the estrogen receptor in neurons: implications for estrogen-induced synapse formation. Proc. Natl. Acad. Sci. USA 98, 7093–7100.10.1073/pnas.121146898Search in Google Scholar PubMed PubMed Central

McKenna, N.J. and O’Malley, B.W. (2002). Minireview: nuclear receptor coactivators – an update. Endocrinology 143, 2461–2465.10.1210/endo.143.7.8892Search in Google Scholar

Melcangi, R.C., Magnaghi, V., Galbiati, M., and Martini, L. (2001). Formation and effects of neuroactive steroids in the central and peripheral nervous system. Int. Rev. Neurobiol. 46, 145–176.10.1016/S0074-7742(01)46062-4Search in Google Scholar

Merchenthaler, I., Dellovade, T.L., and Shughrue, P.J. (2003). Neuroprotection by estrogen in animal models of global and focal ischemia. Ann. N.Y. Acad. Sci. 1007, 89–100.10.1196/annals.1286.009Search in Google Scholar PubMed

Micevych, P., Bondar, G., and Kuo, J. (2010). Estrogen actions on neuroendocrine glia. Neuroendocrinology 91, 211–222.10.1159/000289568Search in Google Scholar PubMed PubMed Central

Miller, N.R., Jover, T., Cohen, H.W., Zukin, R.S., and Etgen, A.M. (2005). Estrogen can act via estrogen receptor α and β to protect hippocampal neurons against global ischemia-induced cell death. Endocrinology 146, 3070–3079.10.1210/en.2004-1515Search in Google Scholar PubMed

Mitra, S.W., Hoskin, E., Yudkovitz, J., Pear, L., Wilkinson, H.A., Hayashi, S., Pfaff, D.W., Ogawa, S., Rohrer, S.P., Schaeffer, J.M., et al. (2003). Immunolocalization of estrogen receptor β in the mouse brain: comparison with estrogen receptor α. Endocrinology 144, 2055–2067.10.1210/en.2002-221069Search in Google Scholar PubMed

Mong, J.A., Nunez, J.L., and McCarthy, M.M. (2002). GABA mediates steroid-induced astrocyte differentiation in the neonatal rat hypothalamus. J. Neuroendocrinol. 14, 45–55.10.1046/j.1365-2826.2002.00737.xSearch in Google Scholar PubMed

Morissette, M., Le Saux, M., D’Astous, M., Jourdain, S., Al Sweidi, S., Morin, N., Estrada-Camarena, E., Mendez, P., Garcia-Segura, L.M., and Di Paolo, T. (2008). Contribution of estrogen receptors α and β to the effects of estradiol in the brain. J. Steroid Biochem. Mol. Biol. 108, 327–338.10.1016/j.jsbmb.2007.09.011Search in Google Scholar PubMed

Murata, T., Dietrich, H.H., Xiang, C., and Dacey, R.G. Jr. (2013). G protein-coupled estrogen receptor agonist improves cerebral microvascular function after hypoxia/reoxygenation injury in male and female rats. Stroke 44, 779–785.10.1161/STROKEAHA.112.678177Search in Google Scholar PubMed PubMed Central

Murphy, S.J., McCullough, L.D., and Smith, J.M. (2004). Stroke in the female: role of biological sex and estrogen. ILAR J. 45, 147–159.10.1093/ilar.45.2.147Search in Google Scholar PubMed

Nedergaard, M., Ransom, B., and Goldman, S.A. (2003). New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 26, 523–530.10.1016/j.tins.2003.08.008Search in Google Scholar

Nilsson, S., Makela, S., Treuter, E., Tujague, M., Thomsen, J., Andersson, G., Enmark, E., Pettersson, K., Warner, M., and Gustafsson, J.A. (2001). Mechanisms of estrogen action. Physiol. Rev. 81, 1535–1565.10.1152/physrev.2001.81.4.1535Search in Google Scholar

Panatier, A., Theodosis, D.T., Mothet, J.P., Touquet, B., Pollegioni, L., Poulain, D.A., and Oliet, S.H. (2006). Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell 125, 775–784.10.1016/j.cell.2006.02.051Search in Google Scholar

Parpura, V., Basarsky, T.A., Liu, F., Jeftinija, K., Jeftinija, S., and Haydon, P.G. (1994). Glutamate-mediated astrocyte-neuron signalling. Nature 369, 744–747.10.1038/369744a0Search in Google Scholar

Pawlak, J., Brito, V., Kuppers, E., and Beyer, C. (2005). Regulation of glutamate transporter GLAST and GLT-1 expression in astrocytes by estrogen. Brain. Res. Mol. Brain Res. 138, 1–7.10.1016/j.molbrainres.2004.10.043Search in Google Scholar

Pellerin, L. and Magistretti, P.J. (2004). Neuroenergetics: calling upon astrocytes to satisfy hungry neurons. Neuroscientist 10, 53–62.10.1177/1073858403260159Search in Google Scholar

Perea, G., Navarrete, M., and Araque, A. (2009). Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 32, 421–431.10.1016/j.tins.2009.05.001Search in Google Scholar

Perez, S.E., Chen, E.Y., and Mufson, E.J. (2003). Distribution of estrogen receptor α and β immunoreactive profiles in the postnatal rat brain. Brain Res. Dev. Brain Res. 145, 117–139.10.1016/S0165-3806(03)00223-2Search in Google Scholar

Prencipe, M., Ferretti, C., Casini, A.R., Santini, M., Giubilei, F., and Culasso, F. (1997). Stroke, disability, and dementia: results of a population survey. Stroke 28, 531–536.10.1161/01.STR.28.3.531Search in Google Scholar PubMed

Rao, S.P. and Sikdar, S.K. (2006). Astrocytes in 17β-estradiol treated mixed hippocampal cultures show attenuated calcium response to neuronal activity. Glia 53, 817–826.10.1002/glia.20341Search in Google Scholar PubMed

Revankar, C.M., Cimino, D.F., Sklar, L.A., Arterburn, J.B., and Prossnitz, E.R. (2005). A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307, 1625–1630.10.1126/science.1106943Search in Google Scholar PubMed

Roof, R.L., and Hall, E.D. (2000). Estrogen-related gender difference in survival rate and cortical blood flow after impact-acceleration head injury in rats. J. Neurotrauma 17, 1155–1169.10.1089/neu.2000.17.1155Search in Google Scholar PubMed

Roquer, J., Campello, A.R., and Gomis, M. (2003). Sex differences in first-ever acute stroke. Stroke 34, 1581–1585.10.1161/01.STR.0000078562.82918.F6Search in Google Scholar PubMed

Rozovsky, I., Wei, M., Stone, D.J., Zanjani, H., Anderson, C.P., Morgan, T.E., and Finch, C.E. (2002). Estradiol (E2) enhances neurite outgrowth by repressing glial fibrillary acidic protein expression and reorganizing laminin. Endocrinology 143, 636–646.10.1210/endo.143.2.8615Search in Google Scholar PubMed

Rutkowsky, J.M., Wallace, B.K., Wise, P.M., and O’Donnell, M.E. (2011). Effects of estradiol on ischemic factor-induced astrocyte swelling and AQP4 protein abundance. Am. J. Physiol. Cell Physiol. 301, C204–C212.10.1152/ajpcell.00399.2010Search in Google Scholar PubMed PubMed Central

Sampei, K., Goto, S., Alkayed, N.J., Crain, B.J., Korach, K.S., Traystman, R.J., Demas, G.E., Nelson, R.J., and Hurn, P.D. (2000). Stroke in estrogen receptor-α-deficient mice. Stroke 31, 738–743; discussion 744.10.1161/01.STR.31.3.738Search in Google Scholar

Santos-Galindo, M., Acaz-Fonseca, E., Bellini, M.J., and Garcia-Segura, L.M. (2011). Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide. Biol. Sex Differ. 2, 7.10.1186/2042-6410-2-7Search in Google Scholar PubMed PubMed Central

Sawada, M., Alkayed, N.J., Goto, S., Crain, B.J., Traystman, R.J., Shaivitz, A., Nelson, R.J., and Hurn, P.D. (2000). Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse. J. Cereb. Blood Flow Metab. 20, 112–118.10.1097/00004647-200001000-00015Search in Google Scholar PubMed

Schwarz, J.M. and Bilbo, S.D. (2012). Sex, glia, and development: interactions in health and disease. Horm. Behav. 62, 243–253.10.1016/j.yhbeh.2012.02.018Search in Google Scholar PubMed PubMed Central

Selvamani, A. and Sohrabji, F. (2010a). Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats. Neurobiol. Aging 31, 1618–1628.10.1016/j.neurobiolaging.2008.08.014Search in Google Scholar PubMed PubMed Central

Selvamani, A. and Sohrabji, F. (2010b). The neurotoxic effects of estrogen on ischemic stroke in older female rats is associated with age-dependent loss of insulin-like growth factor-1. J. Neurosci. 30, 6852–6861.10.1523/JNEUROSCI.0761-10.2010Search in Google Scholar

Shughrue, P.J. and Merchenthaler, I. (2000). Estrogen is more than just a “sex hormone”: novel sites for estrogen action in the hippocampus and cerebral cortex. Front. Neuroendocrinol. 21, 95–101.10.1006/frne.1999.0190Search in Google Scholar

Shughrue, P.J., Lane, M.V., and Merchenthaler, I. (1997). Comparative distribution of estrogen receptor-α and -β mRNA in the rat central nervous system. J. Comp. Neurol. 388, 507–525.10.1002/(SICI)1096-9861(19971201)388:4<507::AID-CNE1>3.0.CO;2-6Search in Google Scholar

Sims, N.R. and Muyderman, H. (2010). Mitochondria, oxidative metabolism and cell death in stroke. Biochim. Biophys. Acta 1802, 80–91.10.1016/j.bbadis.2009.09.003Search in Google Scholar

Singer, C.A., Figueroa-Masot, X.A., Batchelor, R.H., and Dorsa, D.M. (1999). The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J. Neurosci. 19, 2455–2463.10.1523/JNEUROSCI.19-07-02455.1999Search in Google Scholar

Singh, M., Setalo, G. Jr., Guan, X., Frail, D.E., and Toran-Allerand, C.D. (2000). Estrogen-induced activation of the mitogen-activated protein kinase cascade in the cerebral cortex of estrogen receptor-α knock-out mice. J. Neurosci. 20, 1694–1700.10.1523/JNEUROSCI.20-05-01694.2000Search in Google Scholar

Smith, C.C. and McMahon, L.L. (2006). Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors. J. Neurosci. 26, 8517–8522.10.1523/JNEUROSCI.5279-05.2006Search in Google Scholar

Sohrabji, F., Miranda, R.C., and Toran-Allerand, C.D. (1995). Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor. Proc. Natl. Acad. Sci. USA 92, 11110–11114.10.1073/pnas.92.24.11110Search in Google Scholar

Somjen, G.G. (1988). Nervenkitt: notes on the history of the concept of neuroglia. Glia 1, 2–9.10.1002/glia.440010103Search in Google Scholar

Spence, R.D., Hamby, M.E., Umeda, E., Itoh, N., Du, S., Wisdom, A.J., Cao, Y., Bondar, G., Lam, J., Ao, Y., et al. (2011). Neuroprotection mediated through estrogen receptor-α in astrocytes. Proc. Natl. Acad. Sci. USA 108, 8867–8872.10.1073/pnas.1103833108Search in Google Scholar

Stirone, C., Duckles, S.P., and Krause, D.N. (2003). Multiple forms of estrogen receptor-α in cerebral blood vessels: regulation by estrogen. Am. J. Physiol. Endocrinol. Metab. 284, E184–E192.10.1152/ajpendo.00165.2002Search in Google Scholar PubMed

Sundar Boyalla, S., Barbara Victor, M., Roemgens, A., Beyer, C., and Arnold, S. (2011). Sex- and brain region-specific role of cytochrome c oxidase in 1-methyl-4-phenylpyridinium-mediated astrocyte vulnerability. J. Neurosci. Res. 89, 2068–2082.10.1002/jnr.22669Search in Google Scholar PubMed

Suuronen, T., Ojala, J., Hyttinen, J.M., Kaarniranta, K., Thornell, A., Kyrylenko, S., Salminen, A. (2008). Regulation of ER α signaling pathway in neuronal HN10 cells: role of protein acetylation and Hsp90. Neurochem. Res. 33, 1768–1775.10.1007/s11064-008-9622-zSearch in Google Scholar PubMed

Suzuki, S., Brown, C.M., Dela Cruz, C.D., Yang, E., Bridwell, D.A., and Wise, P.M. (2007). Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions. Proc. Natl. Acad. Sci. USA 104, 6013–6018.10.1073/pnas.0610394104Search in Google Scholar PubMed PubMed Central

Takano, T., Oberheim, N., Cotrina, M.L., and Nedergaard, M. (2009). Astrocytes and ischemic injury. Stroke 40, S8–S12.10.1161/STROKEAHA.108.533166Search in Google Scholar PubMed PubMed Central

Tan, X.J., Dai, Y.B., Wu, W.F., Kim, H.J., Barros, R.P., Richardson, T.I., Yaden, B.C., Warner, M., McKinzie, D.L., Krishnan, V., et al. (2012). Reduction of dendritic spines and elevation of GABAergic signaling in the brains of mice treated with an estrogen receptor β ligand. Proc. Natl. Acad. Sci. USA 109, 1708–1712.10.1073/pnas.1121162109Search in Google Scholar PubMed PubMed Central

Tapia-Gonzalez, S., Carrero, P., Pernia, O., Garcia-Segura, L.M., and Diz-Chaves, Y. (2008). Selective oestrogen receptor (ER) modulators reduce microglia reactivity in vivo after peripheral inflammation: potential role of microglial ERs. J. Endocrinol. 198, 219–230.10.1677/JOE-07-0294Search in Google Scholar PubMed

Tasker, J.G., Oliet, S.H., Bains, J.S., Brown, C.H., and Stern, J.E. (2012). Glial regulation of neuronal function: from synapse to systems physiology. J. Neuroendocrinol. 24, 566–576.10.1111/j.1365-2826.2011.02259.xSearch in Google Scholar PubMed PubMed Central

Tenenbaum, M., Azab, A.N., and Kaplanski, J. (2007). Effects of estrogen against LPS-induced inflammation and toxicity in primary rat glial and neuronal cultures. J. Endotoxin Res. 13, 158–166.10.1177/0968051907080428Search in Google Scholar PubMed

Tomas-Camardiel, M., Venero, J.L., Herrera, A.J., De Pablos, R.M., Pintor-Toro, J.A., Machado, A., and Cano, J. (2005). Blood-brain barrier disruption highly induces aquaporin-4 mRNA and protein in perivascular and parenchymal astrocytes: protective effect by estradiol treatment in ovariectomized animals. J. Neurosci. Res. 80, 235–246.10.1002/jnr.20443Search in Google Scholar PubMed

Toung, T.J., Chen, T.Y., Littleton-Kearney, M.T., Hurn, P.D., and Murphy, S.J. (2004). Effects of combined estrogen and progesterone on brain infarction in reproductively senescent female rats. J. Cereb. Blood Flow Metab. 24, 1160–1166.10.1097/01.WCB.0000135594.13576.D2Search in Google Scholar

Turgeon, J.L., Carr, M.C., Maki, P.M., Mendelsohn, M.E., and Wise, P.M. (2006). Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: insights from basic science and clinical studies. Endocr. Rev. 27, 575–605.10.1210/er.2005-0020Search in Google Scholar

Vegeto, E., Belcredito, S., Ghisletti, S., Meda, C., Etteri, S., and Maggi, A. (2006). The endogenous estrogen status regulates microglia reactivity in animal models of neuroinflammation. Endocrinology 147, 2263–2272.10.1210/en.2005-1330Search in Google Scholar

Wappler, E.A., Felszeghy, K., Szilagyi, G., Gal, A., Skopal, J., Mehra, R.D., Nyakas, C., and Nagy, Z. (2010). Neuroprotective effects of estrogen treatment on ischemia-induced behavioural deficits in ovariectomized gerbils at different ages. Behav. Brain Res. 209, 42–48.10.1016/j.bbr.2010.01.010Search in Google Scholar

Wilson, M.E., Dubal, D.B., and Wise, P.M. (2000). Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors. Brain Res. 873, 235–242.10.1016/S0006-8993(00)02479-3Search in Google Scholar

Wu, D.C., Xiao, X.Q., Ng, A.K., Chen, P.M., Chung, W., Lee, N.T., Carlier, P.R., Pang, Y.P., Yu, A.C., and Han, Y.F. (2000). Protection against ischemic injury in primary cultured mouse astrocytes by bis(7)-tacrine, a novel acetylcholinesterase inhibitor [corrected]. Neurosci. Lett. 288, 95–98.10.1016/S0304-3940(00)01198-8Search in Google Scholar

Wu, T.W., Wang, J.M., Chen, S., and Brinton, R.D. (2005). 17β-estradiol induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expression in rat hippocampal neurons: a potential initiation mechanism for estrogen-induced neuroprotection. Neuroscience 135, 59–72.10.1016/j.neuroscience.2004.12.027Search in Google Scholar PubMed

Xu, Z.C., Chwang, W., Li, X., Chen, X., and He, P. (1999). Gender difference in dopamine concentration and postischemic neuronal damage in neostriatum after unilateral dopamine depletion. Exp. Neurol. 158, 182–191.10.1006/exnr.1999.7074Search in Google Scholar PubMed

Yang, S.H., Liu, R., Perez, E.J., Wang, X., and Simpkins, J.W. (2005). Estrogens as protectants of the neurovascular unit against ischemic stroke. Curr. Drug Targets CNS Neurol. Disord. 4, 169–177.10.2174/1568007053544174Search in Google Scholar PubMed

Yi, J.M., Kwon, H.Y., Cho, J.Y., and Lee, Y.J. (2009). Estrogen and hypoxia regulate estrogen receptor α in a synergistic manner. Biochem. Biophys. Res. Commun. 378, 842–846.10.1016/j.bbrc.2008.11.142Search in Google Scholar PubMed

Zhang, J.Q., Cai, W.Q., Zhou, D.S., and Su, B.Y. (2002a). Distribution and differences of estrogen receptor β immunoreactivity in the brain of adult male and female rats. Brain Res. 935, 73–80.10.1016/S0006-8993(02)02460-5Search in Google Scholar

Zhang, L., Li, B., Zhao, W., Chang, Y.H., Ma, W., Dragan, M., Barker, J.L., Hu, Q., and Rubinow, D.R. (2002b). Sex-related differences in MAPKs activation in rat astrocytes: effects of estrogen on cell death. Brain Res. Mol. Brain Res. 103, 1–11.10.1016/S0169-328X(02)00130-4Search in Google Scholar

Zhang, Q.G., Raz, L., Wang, R., Han, D., De Sevilla, L., Yang, F., Vadlamudi, R.K., and Brann, D.W. (2009). Estrogen attenuates ischemic oxidative damage via an estrogen receptor α-mediated inhibition of NADPH oxidase activation. J. Neurosci. 29, 13823–13836.10.1523/JNEUROSCI.3574-09.2009Search in Google Scholar PubMed PubMed Central

Zhang, B., Subramanian, S., Dziennis, S., Jia, J., Uchida, M., Akiyoshi, K., Migliati, E., Lewis, A.D., Vandenbark, A.A., Offner, H., et al. (2010). Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke. J. Immunol. 184, 4087–4094.10.4049/jimmunol.0902339Search in Google Scholar PubMed PubMed Central

Zhang, Q.G., Han, D., Wang, R.M., Dong, Y., Yang, F., Vadlamudi, R.K., and Brann, D.W. (2011). C terminus of Hsc70-interacting protein (CHIP)-mediated degradation of hippocampal estrogen receptor-α and the critical period hypothesis of estrogen neuroprotection. Proc. Natl. Acad. Sci. USA 108, E617–E624.10.1073/pnas.1104391108Search in Google Scholar PubMed PubMed Central

Zhao, L. and Brinton, R.D. (2007). Estrogen receptor α and β differentially regulate intracellular Ca2+ dynamics leading to ERK phosphorylation and estrogen neuroprotection in hippocampal neurons. Brain Res. 1172, 48–59.10.1016/j.brainres.2007.06.092Search in Google Scholar PubMed

Received: 2013-11-18
Accepted: 2014-1-29
Published Online: 2014-2-22
Published in Print: 2014-4-1

©2014 by Walter de Gruyter Berlin/Boston

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