Insulin-like growth factor-I receptors and estrogen receptors interact in the promotion of neuronal survival and neuroprotection

ANDO'S, S., PANNO, M. L., SALERNO, M., SISCI, D., MAURO, L., LANZINO, M. & SURMACZ, E. (1998) Role of IRS-1 signaling in insulin-induced modulation of estrogen receptors in breast cancer cells. Biochemical and Biophysical Research Communications 253, 315–319. ARIMATSU, Y. & HATANAKA, H. (1986) Estrogen treatment enhances survival of cultured fetal rat amygdala neurons in a defined medium. Developmental Brain Research 26, 151–159. ARONICA, S. M. & KATZENELLENBOGEN, B. S. (1993) Stimulation of estrogen receptor-mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate, and insulin-like growth factor-I. Molecular Endocrinology 7, 743–752. AZCOITIA, I., SIERRA, A. & GARCIA-SEGURA, L. M. (1998) Estradiol prevents kainic acid-induced neuronal loss in the rat dentate gyrus. NeuroReport 9, 3075–3079. AZCOITIA, I., SIERRA, A. & GARCIA-SEGURA, L. M. (1999b) Neuroprotective effects of estradiol in the adult rat hippocampus: Interaction with insulin-like growth factor-I signalling. Journal of Neuroscience Research 58, 815–822. AZCOITIA, I., FERNANDEZ-GALAZ, C., SIERRA, A. & GARCIA-SEGURA, L. M. (1999a) Gonadal hormones affect neuronal vulnerability to excitotoxin-induced degeneration. Journal of Neurocytology 28, 699–710. BASKIN, D. G., WILCOX, B. J., FIGLEWICZ, D. P. & DORSA, D. M. (1988) Insulin and insulin-like growth factors in the CNS. Trends in Neuroscience 11, 608–612. BECK, K. D., POWELL-BRAXTON, L., WIDMER, H. R., VALVERDE, J. & HEFTI, F. (1995) Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 14, 717–730. BEHL, C. & HOLSBOER, F. (1999) The female sex hormone oestrogen as a neuroprotectant. Trends in Pharmacological Sciences 20, 441–444. BEHL, C. & MANTHEY, D. (2000) Neuroprotective activities of estrogen: An update. Journal of Neurocytology 29, 351–358. BEHL, C., SKUTELLA, T., LEZOUALC'H, F., POST, A., WIDMANN, M., NEWTON, C. J. & HOLSBOER, F. (1997) Neuroprotection against oxidative stress by estrogens: Structure-activity relationship. Molecular Pharmacology 51, 535–541. BEHL, C., WIDMANN, M., TRAPP, T. & HOLSBOER, F. (1995) 17-? estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochemical and Biophysical Research Communications 216, 473–482. BEILHARZ, E. J., RUSSO, V. C., BUTLER, G., BAKER, N. L., CONNOR, B., SIRIMANNE, E. S., DRAGUNOW, M., WERTHER, G. A., GLUCKMAN, P. D., WILLIAMS, C. E. & SCHEEPENS, A. (1998) Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury. Molecular Brain Research 59, 119–134. BRINTON, R. D, TRAN, J., PROFFITT, P. & MONTOYA, M. (1997) 17 ?-Estradiol enhances the outgrowth and survival of neocortical neurons in culture. Neurochemical Research 22, 1339–1351. BUCKMASTER, P. S. & DUDEK, F. E. (1997) Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. Journal of Comparative Neurology 385, 385–404. CARDONA-GOMEZ, G. P., DONCARLOS, L. L. & GARCIA-SEGURA, L. M. (2000) Insulin-like growth factor receptors and estrogen receptors colocalize in female rat brain. Neuroscience 99, 751–760. CARRO, E., NUÑEZ, A., BUSIGUINA, S. & TORRES-ALEMAN, I. (2000) Circulating insulin-like growth factor I mediates effects of exercise on the brain. Journal of Neuroscience 20, 2926–2933. CASTRO-ALAMANCOS, C. A. & TORRES-ALEMÁN, I. (1994) Blockade of eye-blink conditioned responses by an antisense oligonucleotide of insulin-like growth factor I. Proceedings of the National Academy of Sciences of the USA 91, 10203–10207. CHEN, J., ADACHI, N., LIU, K. & ARAI, T. (1998) The effects of 17?-estradiol on ischemia-induced neuronal damage in the gerbil hippocampus. Neuroscience 87, 817–822. CHENG, H. L. & FELDMAN, E. L. (1998) Bidirectional regulation of p38 kinase and c-Jun N-terminal protein kinase by insulin-like growth factor-I. Journal of Biological Chemistry 273, 14560–14565. CHOWEN, J. A., TORRES-ALEMAN, I. & GARCIA-SEGURA, L. M. (1992) Trophic effects of estradiol on fetal rat hypothalamic neurons. Neuroendocrinology 56, 895–901. CHOWEN-BREED, J., STEINER, R. A. & CLIFTON, D. K. (1989) Sexual dimorphism and testosterone-dependent regulation of somatostatin gene expression in the periventricular nucleus of the rat hypothalamus. Endocrinology 125, 357–362. CULMSEE, C., VEDDER, H., RAVATI, A., JUNKER, V., OTTO, D., AHLEMEYER, B., KRIEG, J. C. & KRIEGLSTEIN, J. (1999) Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: Evidence for a receptor-independent antioxidative mechanism. Journal of Cerebral Blood Flow and Metabolism 19, 1263–1269. DAUGHADAY, W. H. & ROTWEIN, P. (1989) Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocrine Reviews 10, 68–91. DE PABLO, F. & DE LA ROSA, E. J. (1995) The developing CNS: A scenario for the action of proinsulin, insulin and insulin-like growth factors. Trends in Neuroscience 18, 143–150. DLUZEN, D. E. (1997) Estrogen decreases corpus striatal neurotoxicity in response to 6-hydroxydopamine. Brain Research 767, 340–344. DLUZEN, D. E. (2000) Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system. Journal of Neurocytology 29, 387–399. DLUZEN, D. E., MCDERMOTT, J. L. & LIU, B. (1996a) Estrogen as a neuroprotectant against MPTP-induced neurotoxicity in C57/B1 mice. Neurotoxicology and Teratology 18, 603–606. DLUZEN, D. E., MCDERMOTT, J. L. & LIU, B. (1996b) Estrogen alters MPTP-induced neurotoxicity in female mice: Effects on striatal dopamine concentrations and release. Journal of Neurochemistry 66, 658–666. DONG, L., WANG, W., WANG, F., STONER, M., REED, J. C., HARIGAI, M., SAMUDIO, I., KLADDE, M. P., VYHLIDAL, C. & SAFE, S. (1999) Mechanisms of transcriptional activation of bcl-2 gene expression by 17?-estradiol in breast cancer cells. Journal of Biological Chemistry 274, 32099–32107. DORÉ, S., KAR, S. & QUIRION, R. (1997) Rediscovering an old friend, IGF-I: Potential use in the treatment of neurodegenerative diseases. Trends in Neuroscience 20, 326–331. DUBAL, D. B., KASHON, M. L., PETTIGREW, L. C., REN, J. M., FINKLESTEIN, S. P., RAU, S. W. & WISE, P. M. (1998) Estradiol protects against ischemic injury. Journal of Cerebral Blood Flow and Metabolism 18, 1253–1258. DUBAL, D. B., SHUGHRUE, P. J., WILSON, M. E., MERCHENTHALER, I. & WISE, P. M. (1999) Estradiol modulates bcl-2 in cerebral ischemia: A potential role for estrogen receptors. Journal of Neuroscience 19, 6385–6393. DUEÑAS, M., LUQUIN, S., CHOWEN, J. A., TORRESALEMAN, I., NAFTOLIN, F. & GARCIA-SEGURA L. M. (1994) Gonadal hormone regulation of insulin-like growth factor-I-like immunoreactivity in hypothalamic astroglia of developing and adult rats. Neuroendocrinology 59, 528–538. DUEÑAS, M., TORRES-ALEMAN, I., NAFTOLIN, F. & GARCIA-SEGURA, L. M. (1996) Interaction of insulin-like growth factor-1 and estradiol signaling pathways on hypothalamic neuronal differentiation. Neuroscience 74, 531–539. FAIVRE-BAUMAN, A., ROSENBAUM, E., PUYMIRAT, J., GROUSELLE, D. & TIXIER-VIDAL, A. (1981) Differentiation of fetal mouse hypothalamic cells in serum-free medium. Developmental Neuroscience 4, 118–129. FERNANDEZ, A. M., GARCIA-ESTRADA, J., GARCIA-SEGURA, L. M. & TORRES-ALEMAN, I. (1997) Insulin-like growth factor I modulates c-Fos induction and astrocytosis in response to neurotoxic insult. Neuroscience 76, 117–122. FERNANDEZ, A. M., GONZALEZ DE LA VEGA, A. G., PLANAS, B. & TORRES-ALEMAN, I. (1999) Neuroprotective actions of peripherally administered insulin-like growth factor I in the injured olivo-cerebellar pathway. European Journal of Neuroscience 11, 2019–2030. FERNANDEZ, A. M., GONZALEZ DE LA VEGA, A. & TORRES-ALEMAN, I. (1998) Insulin-like growth factor restores motor coordination in a rat model of cerebellar ataxia. Proceedings of the National Academy of Sciences of the USA 95, 1253–1258. FERNANDEZ-GALAZ, M. C., NAFTOLIN, F. & GARCIA-SEGURA, L. M. (1999) Phasic synaptic remodeling of the rat arcuate nucleus during the estrous cycle depends on insulin-like growth factor-I receptor activation. Journal of Neuroscience Research 55, 286–292. FILLIT, H. (1984) Observations in a preliminary open trial of estradiol therapy for senile dementia-Alzheimer's type. Psychoneuroendocrinology 11, 337–345. GARCIA-ESTRADA, J., GARCIA-SEGURA, L. M. & TORRES-ALEMAN, I. (1992) Expression of insulin-like growth factor I by astrocytes in response to injury. Brain Research 592, 343–347. GARCIA-SEGURA, L. M., CARDONA-GÓMEZ, P., NAFTOLIN, F. & CHOWEN, J. A. (1998) Estradiol upregulates Bcl-2 expression in adult brain neurons. NeuroReport 9, 593–597. GARCIA-SEGURA, L. M., NAFTOLIN, F., HUTCHISON, J. B., AZCOITIA, I. & CHOWEN, J. A. (1999) Role of astroglia in estrogen regulation of synaptic plasticity and brain repair. Journal of Neurobiology 40, 574–584. GIBBS, R. B. (1998) Levels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous cycle and increase in response to acute hormone replacement. Brain Research 787, 259–268. GIBBS, R. B., WU, D., HERSH, L. B. & PFAFF, D. W. (1994) Effects of estrogen replacement on the relative levels of choline acetyltransferase, trkA, and nerve growth factor messenger RNAs in the basal forebrain and hippocampal formation of adult rats. Experimental Neurology 129, 70–80. GOLLAPUDI, L. & OBLINGER, M. M. (1999a) Stable transfection of PC12 cells with estrogen receptor (ER?): Protective effects of estrogen on cell survival after serum deprivation. Journal of Neuroscience Research 56, 99–108. GOLLAPUDI, L. & OBLINGER, M. M. (1999b) Estrogen and NGF synergistically protect terminally differentiated ER?-transfected PC12 cells from apoptosis. Journal of Neuroscience Research 56, 471–481. GOMEZ-MANCILLA, B. & BEDARD, P. J. (1992) Effect of estrogen and progesterone on L-dopa induced dyskinesia in MPTP-treated monkeys. Neuroscience Letters 135, 129–132. HAFNER, F., HOLLER, E. & VON ANGERER, E. (1996) Effect of growth factors on estrogen receptor mediated gene expression. Journal of Steroid Biochemistry and Molecular Biology 58, 385–393. HECK, S., LEZOULAC'H, F., ENGERT, S. & BEHL, C. (1999) Insulin-like growth factor-1-mediated neuroprotection against oxidative stress is associated with activation of nuclear factor kappaB. Journal of Biological Chemistry 274, 9828–9835. HENDERSON, V. W., PAGANINI-HILL, A., EMANUEL, C. K., DUNN, M. E. & BUCKWALTER, G. (1994) Estrogen replacement therapy in older women. Archives of Neurology 51, 896–900. HINEY, J. K., SRIVASTAVA, V., NYBERG, C. L., OJEDA, S. R. & DEES, W. L. (1996) Insulin-like growth factor I of peripheral origin acts centrally to accelerate the initiation of female puberty. Endocrinology 137, 3717–3728. HONJO, H., OGINO, Y., NAITOH, K., URABE, M., KITAWAKI, J., YASUDA, J., YAMAMOTO, T., ISHIHARA, S., OKADA, H., YONEZAWA, T., HAYASHI, K. & NAMBARA, T. (1989) In vivo effects by estrone sulfate on the central nervous system senile dementia (Alzheimer's type). Journal of Steroid Biochemistry 34, 521–525. HUYNH, H., NICKERSON, T., POLLAK, M. & YANG, X. (1996) Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182780. Clinical Cancer Research 2, 2037–2042. IGNAR-TROWBRIDGE, D. M., PIMENTEL, M., PARKER, M. G., MCLACHLAN, J. A. & KORACH, K. S. (1996) Peptide growth factor cross-talk with the estrogen receptor requires the A/B domain and occurs independently of protein kinase C or estradiol. Endocrinology 137, 1735–1744. JONES, J. I. & CLEMMONS, D. R. (1995) Insulin-like growth factors and their binding proteins: Biological actions. Endocrine Reviews 16, 3–34. JORDAN, C. L. (1999) Glia as mediators of steroid hormone action on the nervous system: An overview. Journal of Neurobiology 40, 434–445. KAR, S., SETO, D., DORE, S., CHABOT, J. G. & QUIRION, R. (1997) Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation. Neuroscience 80, 1041–1055. KATO, S., ENDOH, H., MASUHIRO, Y., KITAMOTO, T., UCHIYAMA, S., SASAKI, H., MASUSHIGE, S., GOTOH, Y., NISHIDA, E. & KAWASHIMA, H. (1995) Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270, 1491–1494. KERMER, P., KLOCKER, N., LABES, M. & BAHR, M. (2000) Insulin-like growth factor-I protects axotomized rat retinal ganglion cells from secondary death via PI3-K-dependent Akt phosphorylation and inhibition of caspase-3 in vivo. Journal of Neuroscience 20, 722–728. KUIPER, G. G. J. M., ENMARK, E., PELTO-HUIKKO, M., NILSSON, S. & GUSTAFSSON, J.-A. (1996) Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proceedings of the National Academy of Sciences of the USA 93, 5925–5930. KUIPER, G. G. J. M., SHUGRUE, P. J., PELTKOHUIKKO, M., MERCHENTHALER, I. & GUSTAFSSON, J.-A. (1998) The estrogen receptor ? subtype: A novel mediator of estrogen action in neuroendocrine systems. Frontiers in Neuroendocrinology 19, 253–286. LAMBERTS, S. W., VAN DEN BELD, A. W. & VAN DER LELY. A. J. (1997) The endocrinology of aging. Science 278, 419–424. LEROITH, D., WERNER, H., BEITNER-JOHNSON, D. & ROBERTS, C. D. (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocrine Reviews 16, 143–163. MA, Z. Q., SANTAGATI, S., PATRONE, C., POLLIO, G., VEGETO, E. & MAGGI, A. (1994) Insulin-like growth factors activate estrogen receptor to control the growth and differentiation of the human neuroblastoma cell line SK-ER3. Molecular Endocrinology 8, 910–918. MCMILLAN, P. J., SINGER, C. A. & DORSA, D. M. (1996) The effect of ovariectomy and estrogen replacement on trkA and choline acetyltransferase mRNA expression in the basal forebrain of the adult female Sprague-Dawley rat. Journal of Neuroscience 16, 1860–1865. MIGLIACCIO, A., DI, D. M., CASTORIA, G., DE FALCO, A., BONTEMPO, P., NOLA, E. & AURICCHIO, F. (1996) Tyrosine kinase/p21ras/MAP-Kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO Journal 15, 1292–1300. MIRANDA, R. C., SOHRABJI, F. & TORAN-ALLERAND, D. (1994) Interactions of estrogen with the neurotrophins and their receptors during neural development. Hormones and Behavior 28, 367–375. MONG, J. A. & MCCARTHY, M. M. (1999) Steroid-induced developmental plasticity in hypothalamic astrocytes: Implications for synaptic patterning. Journal of Neurobiology 40, 602–619. MURPHY, D. D., COLE, N. B. & SEGAL, M. (1998) Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons. Proceedings of the National Academy of Sciences of the USA 95, 11412–11417. NEWTON, C. J., BURIC, R., TRAPP, T., BROCKMEIER, S., PAGOTTO, U. & STALLA, G. K. (1994) The unligand estrogen receptor (ER) transduces growth factor signals. Journal of Steroid Biochemistry and Molecular Biology 48, 481–486. OHKURA, T., ISSE, K., AKAZAWA, K., HAMAMOTO, M., YAOI, Y. & HAGINO, N. (1994) Evaluation of estrogen treatment in female patients with dementia of the Alzheimer type. Endocrine Journal 41, 361–371. OJEDA, S. R. & MA, Y. J. (1999) Glial-neuronal interactions in the neuroendocrine control of mammalian puberty: Facilitatory effects of gonadal steroids. Journal of Neurobiology 40, 528–540. PAGANINI-HILL, A. & HENDERSON, V. W. (1994) Estrogen deficiency and risk of AD in women. American Journal of Epidemiology 140, 256–261. PATRONE, C., ANDERSSON, S., KORHONEN, L. & LINDHOLM, D. (1999) Estrogen receptor-dependent regulation of sensory neuron survival in developing dorsal root ganglion. Proceedings of the National Academy of Sciences of the USA 96, 10905–10910. PATRONE, C., MA, Z. Q., POLLIO, G., AGRATI, P., PARKER, M. G. & MAGGI, A. (1996) Cross-coupling between insulin and estrogen receptor in human neuroblastoma cells. Molecular Endocrinology 10, 499–507. PELLIGRINO, D. A., SANTIZO, R., BAUGHMAN, V. L. & WANG, Q. (1998) Cerebral vasodilating capacity during forebrain ischemia: Effects of chronic estrogen depletion and repletion and the role of neuronal nitric oxide synthase. NeuroReport 9, 3285–3291. PIETRZKOWSKI, Z., WERMICKE, D., PORCU, P., JAMESON, B. A. & BASERGA, R. (1992) Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor I. Cancer Research 52, 6447–6451. PUGAZHENTHI, S., MILLER, E., SABLE, C., YOUNG, P., HEIDENREICH, K. A., BOXER, L. M. & REUSCH, J. E. (1999) Insulin-like growth factor-I induces bcl-2 promoter through the transcription factor cAMP-response element-binding protein. Journal of Biological Chemistry 274, 27529–27535. RABBANI, O., PANICKAR, K. S., RAJAKUMAR, G., KING, M. A., BODOR, N., MEYER, E. M. & SIMPKINS, J. W. (1997) 17 ?-estradiol attenuates fimbrial lesion-induced decline of ChAT-immunoreactive neurons in the rat medial septum. Experimental Neurology 146, 179–186. REGAN, R. F. & GUO, Y. (1997) Estrogens attenuate neuronal injury due to hemoglobin, chemical hypoxia, and excitatory amino acids in murine cortical cultures. Brain Research 764, 133–140. REINHARDT, R. R. & BONDY, C. A. (1994) Insulin-like growth factors cross the blood-brain barrier. Endocrinology 135, 1753–1761. RICHARDS, R. G., WALKER, M. P., SEBASTIAN, J. & DIAUGUSTINE, R. P. (1998) Insulin-like growth factor-1 (IGF-I) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-I (m/m) mouse. Journal of Biological Chemistry 273, 11962–11969. RUSA, R., ALKAYED, N. J., CRAIN, B. J., TRAYSTMAN, R. J., KIMES, A. S., LONDON, E. D., KLAUS, J. A. & HURN, P. D. (1999) 17?-estradiol reduces stroke injury in estrogen-deficient female animals. Stroke 30, 1665–1670. SAHLIN, L., NORSTEDT, G. & ERIKSSON, H. (1994) Estrogen regulation of the estrogen receptor and insulin-like growth factor-I in the rat uterus: A potential coupling between effects of estrogen and IGF-I. Steroids 59, 421–430. SALERNO, M, SISCI, D., MAURO, L., GUVAKOVA, M. A., ANDO'S, S. & SURMACZ, E. (1999) Insulin receptor substrate 1 is a target for the pure antiestrogen ICI 182, 780 in breast cancer cells. International Journal of Cancer 81, 229–304. SAWADA, H., IBI, M., KIHARA, T., URUSHITANI, M., AKAIKE, A. & SHIMOHAMA, S. (1998) Estradiol protects mesencephalic dopaminergic neurons from oxidative stress-induced neuronal death. Journal of Neuroscience Research 54, 707–719. SCHNEIDER, L. S., FARLOW, M. R., HENDERSON, V. W. & POGODA J. M. (1996) Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease. Neurology 46, 1580–1584. SCULLY, J. L. & OTTEN, U. (1995) Neurotrophin expression modulated by glucocorticoids and oestrogen in immortalized hippocampal neurons. Molecular Brain Research 31, 158–164. SHUGRUE, P. J., LANE, M. V. & MERCHENTHALER, I. (1997) Comparative distribution of estrogen receptor-? and-? mRNA in the rat central nervous system. Journal of Comparative Neurology 388, 507–525. SIMPKINS, J. W., RAJAKUMAR, G., ZHANG, Y. Q., SIMPKINS, C. E., GREENWALD, D., YU, C. J., BODOR, N. & DAY, A. L. (1997) Estrogens may reduce mortality and ischemic damage caused by middle cerebral artery occlusion in the female rat. Journal of Neurosurgery 87, 724–730. SINGER, C. A, FIGEROA-MASOT, X. A., BATCHELOR, R. H. & DORSA, D. M. (1999) The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. Journal of Neuroscience 19, 2455–2463. SINGER, C. A., ROGERS, K. L., STRICKLAND, T. M. & DORSA, D. M. (1996) Estrogen protects primary cortical neurons from glutamate toxicity. Neuroscience Letters 212, 13–16. SINGH, M., MEYER, E. M. & SIMPKINS, J. W. (1995) The effect of ovariectomy and estrogen replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female Sprague Dawley rats. Endocrinology 136, 2320–2324. SINGH, M., SÉTÁLÓ, G., GUAN, X., WARREN, M. & TORAN-ALLERAND, C. D. (1999) Estrogen-induced activation of mitogen-activated protein-kinase in cerebral cortical explants: Convergence of estrogen and neurotrophin signaling pathways. Journal of Neuroscience 19, 1179–1188. SMITH, C. L. (1998) Cross-talk between peptide growth factor and estrogen receptor signaling pathways. Biology of Reproduction 58, 627–632. SOHRABJI, F., GREENE, L. A., MIRANDA, R. C. & TORAN-ALLERAND, C. D. (1994a) Reciprocal regulation of estrogen and NGF receptors by their ligands in PC12 cells. Journal of Neurobiology 25, 974–988. SOHRABJI, F., MIRANDA, R. C. & TORAN-ALLERAND, C. D. (1994b) Estrogen differentially regulates estrogen and nerve growth factor receptor mRNAs in adult sensory neurons. Journal of Neuroscience 14, 459–471. SOHRABJI, F., MIRANDA, R. C. & TORAN-ALLERAND, C. D. (1995) Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor. Proceedings of the National Academy of Sciences of the USA 92, 11110–11114. SPERK, G. (1994) Kainic acid seizures in the rat. Progress in Neurobiology 42, 1–32. SUDO, S., WEN, T. C., DESAKI, J., MATSUDA, S., TANAKA, J., ARAI, T., MAEDA, N. & SAKANAKA, M. (1997) Beta-estradiol protects hippocampal CA1 neurons against transient forebrain ischemia in gerbil. Neuroscience Research 29, 345–354. TAMATANI, M., OGAWA, S. & TOHYAMA, M. (1998) Roles of Bcl-2 and caspases in hypoxia-induced neuronal cell death: A possible neuroprotective mechanism of Role of receptors for IGF-1 and estrogen in neuroprotection 437 peptide growth factors. Molecular Brain Research 15, 27–39. TANG, M. X., JACOBS, D., STERN, Y., MARDER, K., SCHOFIELD, P., GURLAND, B., ANDREWS, H. & MAYEUX, R. (1996) Effect of estrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 348, 429–432. TORAN-ALLERAND, C. D. (1996) Mechanisms of estrogen action during neural development: Mediation by interactions with the neurotrophins and their receptors? Journal of Steroid Biochemistry and Molecular Biology 56, 169–178. TORAN-ALLERAND, C. D., ELLIS, L. & PFENNINGER K. H. (1988) Estrogen and insulin synergism in neurite growth enhancement in vitro: Mediation of steroid effects by interactions with growth factor?. Brain Research 469, 87–100. TORAN-ALLERAND, C. D., MIRANDA, R. C., BENTHAM, W. D., SOHRABJI, F., BROWN, T. J., HOCHBERG, R. B. & MACLUSKY, N. J. (1992) Estrogen receptors colocalize with low-affinity growth factor receptors in cholinergic neurons of the basal forebrain. Proceedings of the National Academy of Sciences of the USA 89, 4668–4672. TORAN-ALLERAND, C. D., SINGH, M. & SETALO, G. (1999) Novel mechanisms of estrogen action in the brain: New players in an old story. Frontiers in Neuroendocrinology 20, 97–121. TORRES-ALEMAN, I., NAFTOLIN, F. & ROBBINS, R. J. (1990) Trophic effects of insulin-like growth factor-I on fetal rat hypothalamic cells in culture. Neuroscience 35, 601–608. TORRES-ALEMAN, I., PONS, S. & AREVALO, M. A. (1994) The insulin-like growth factor I system in the rat cerebellum: Developmental regulation and role in neuronal survival and differentiation. Journal of Neuroscience Research 39, 117–126. TORRES-ALEMAN, I. (1999) Insulin-like growth factors as mediators of functional plasticity in the adult brain. Hormone and Metabolic Research 31, 114–119. TRANQUE, P., NAFTOLIN, F. & ROBBINS, R. (1994) Differential regulation of astrocyte plasminogen activators by insulin-like growth factor-I and epidermal growth factor. Endocrinology 134, 2606–2613. VEDDER, H., ANTHES, N., STUMM, G., WURZ, C., BEHL, C. & KRIEG, J. C. (1999) Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system. Journal of Neurochemistry 72, 2531–2538. WANG, Q., SANTIZO, R., BAUGHMAN, V. L., PELLIGRINO, D. A. & IADECOLA, C. (1999) Estrogen provides neuroprotection in transient forebrain ischemia through perfusion-independent mechanisms in rats. Stroke 30, 630–637. WEAVER, C. E., PARK-CHUNG, M., GIBBS, T. T. & FARB, D. H. (1997) 17?-Estradiol protects against NMDA-induced excitotoxicity by direct inhibition of NMDA receptors. Brain Research 761, 338–341. WISE, P. M., DUBAL, D. B., WILSON, M. E. & RAU, S. W. (2000) Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury. Journal of Neurocytology 29, 401–410. YANG, D. D., KUAN, C. Y., WHITMARSH, A. J., RINCON, M., ZHENG, T. S., DAVIS, R. J., RAKIC, P. & FLAVELL, R. A. (1998) Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 389, 865–870. ZAULYANOV, L. L., GREEN, P. S. & SIMPKINS, J. W. (1999) Glutamate receptor requirement for neuronal cell death from anoxia-reoxygenation: An in vitro model for assessment of the neuroprotective effects of estrogens. Cellular and Molecular. Neurobiology 19, 705–718. ZEITLER, P., ARGENTE, J., CHOWEN-BREED, J. A., CLIFTON, D. K. & STEINER, R. A. (1990) Growth hormone-releasing hormone messenger ribonucleic acid in the hypothalamus of the adult male rat is increased by testosterone. Endocrinology 127, 1362–1368. ZHANG, Y. Q., SHI, J., RAJAKUMAR, G., DAY, A. L. & SIMPKINS, J. W. (1998) Effects of gender and estradiol treatment on focal brain ischemia. Brain Research 784, 321–324.