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PMID: 22133892 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation.

Neuroscience ·Vol. 202 ·2012-01-27 ·Pages 131-46

Spencer-Segal JL, Tsuda MC, Mattei L, Waters EM, Romeo RD, Milner TA, McEwen BS, Ogawa S

Abstract

Estradiol affects hippocampal-dependent spatial memory and underlying structural and electrical synaptic plasticity in female mice and rats. Using estrogen receptor (ER) alpha and beta knockout mice and wild-type littermates, we investigated the role of ERs in estradiol effects on multiple pathways important for hippocampal plasticity and learning. Six hours of estradiol administration increased immunoreactivity for phosphorylated Akt throughout the hippocampal formation, whereas 48 h of estradiol increased immunoreactivity for phosphorylated TrkB receptor. Estradiol effects on phosphorylated Akt and TrkB immunoreactivities were abolished in ER alpha and ER beta knockout mice. Estradiol also had distinct effects on immunoreactivity for post-synaptic density 95 (PSD-95) and brain derived-neurotrophic factor (BDNF) mRNA in ER alpha and beta knockout mice. Thus, estradiol acts through both ERs alpha and beta in several subregions of the hippocampal formation. The different effects of estradiol at 6 and 48 h indicate that several mechanisms of estrogen receptor signaling contribute to this female hormone's influence on hippocampal synaptic plasticity. By further delineating these mechanisms, we will better understand and predict the effects of endogenous and exogenous ovarian steroids on mood, cognition, and other hippocampal-dependent behaviors.

MeSH Terms
Animals Brain-Derived Neurotrophic Factor/biosynthesis,genetics Data Interpretation, Statistical Densitometry Disks Large Homolog 4 Protein Estradiol/pharmacology Estrogen Receptor alpha/drug effects,genetics Estrogen Receptor beta/drug effects,genetics Estrous Cycle/drug effects,physiology Female Guanylate Kinases/metabolism Hippocampus/cytology,drug effects Hormone Replacement Therapy Immunohistochemistry In Situ Hybridization Membrane Proteins/metabolism Mice Mice, Inbred C57BL Mice, Knockout Neural Pathways/drug effects Neuronal Plasticity/drug effects Ovariectomy Proto-Oncogene Proteins c-akt/metabolism Receptor, trkB/biosynthesis,genetics Synapses/drug effects
Chemicals
Brain-Derived Neurotrophic Factor Disks Large Homolog 4 Protein Dlg4 protein, mouse Estrogen Receptor alpha Estrogen Receptor beta Membrane Proteins Estradiol Receptor, trkB Proto-Oncogene Proteins c-akt Guanylate Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Spencer-Segal J L
Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA. [email protected]
Tsuda M C
Mattei L
Waters E M
Romeo R D
Milner T A
McEwen B S
Ogawa S
References (125)
125 references, click to expand
  1. Analysis of transcription and estrogen insensitivity in the female mouse after targeted disruption of the estrogen receptor gene.
    Mol Endocrinol. 1995 Nov;9(11):1441-54 PMID: 8584021
  2. Translational control of long-lasting synaptic plasticity and memory.
    Neuron. 2009 Jan 15;61(1):10-26 PMID: 19146809
  3. Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors.
    J Neurosci. 2006 Aug 16;26(33):8517-22 PMID: 16914677
  4. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats.
    Brain Res. 1994 May 2;644(2):305-12 PMID: 8050041
  5. Associative memory formation increases the observation of dendritic spines in the hippocampus.
    J Neurosci. 2003 Jan 15;23(2):659-65 PMID: 12533625
  6. Expression of estrogen receptor alpha and beta transcripts in female monkey hippocampus and hypothalamus.
    Brain Res. 1998 Mar 30;788(1-2):320-2 PMID: 9555076
  7. Mechanisms of estrogen action.
    Physiol Rev. 2001 Oct;81(4):1535-65 PMID: 11581496
  8. Different modes of hippocampal plasticity in response to estrogen in young and aged female rats.
    Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8071-6 PMID: 11427724
  9. Spatial memory retention is enhanced by acute and continuous estradiol replacement.
    Horm Behav. 2004 Feb;45(2):128-35 PMID: 15019800
  10. Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity.
    J Biol Chem. 2008 Feb 1;283(5):2631-43 PMID: 18057005
  11. Morphometry of a peptidergic transmitter system: dynorphin B-like immunoreactivity in the rat hippocampal mossy fiber pathway before and after seizures.
    Hippocampus. 1999;9(3):255-76 PMID: 10401641
  12. Spine-type densities of hippocampal CA1 neurons vary in proestrus and estrus rats.
    Neurosci Lett. 2005 Apr 29;379(1):52-4 PMID: 15814198
  13. Learning induces long-term potentiation in the hippocampus.
    Science. 2006 Aug 25;313(5790):1093-7 PMID: 16931756
  14. Dendritic spine changes associated with hippocampal long-term synaptic plasticity.
    Nature. 1999 May 6;399(6731):66-70 PMID: 10331391
  15. Intra-hippocampal estradiol infusion enhances memory in ovariectomized rats.
    Neuroreport. 1997 Sep 29;8(14):3009-13 PMID: 9331907
  16. Activation of estrogen receptor-beta regulates hippocampal synaptic plasticity and improves memory.
    Nat Neurosci. 2008 Mar;11(3):334-43 PMID: 18297067
  17. Impact of the selective estrogen receptor modulator, tamoxifen, on neuronal outgrowth and survival following toxic insults associated with aging and Alzheimer's disease.
    Exp Neurol. 2004 Aug;188(2):268-78 PMID: 15246826
  18. Proestrous compared to diestrous wildtype, but not estrogen receptor beta knockout, mice have better performance in the spontaneous alternation and object recognition tasks and reduced anxiety-like behavior in the elevated plus and mirror maze.
    Behav Brain Res. 2009 Jan 23;196(2):254-60 PMID: 18926853
  19. Novel effects of estradiol and estrogen receptor alpha and beta on cognitive function.
    Brain Res. 2000 Nov 17;883(2):258-64 PMID: 11074057
  20. Integration of the extranuclear and nuclear actions of estrogen.
    Mol Endocrinol. 2005 Aug;19(8):1951-9 PMID: 15705661
  21. Disruption of estrogen receptor beta gene impairs spatial learning in female mice.
    Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3996-4001 PMID: 11891272
  22. Estrogen signaling: a subtle balance between ER alpha and ER beta.
    Mol Interv. 2003 Aug;3(5):281-92 PMID: 14993442
  23. Role of the phosphoinositide 3-kinase-Akt-mammalian target of the rapamycin signaling pathway in long-term potentiation and trace fear conditioning memory in rat medial prefrontal cortex.
    Learn Mem. 2008 Oct 02;15(10):762-76 PMID: 18832563
  24. Selective estrogen receptor modulator effects in the rat brain.
    Neuroendocrinology. 2002 Jan;75(1):24-33 PMID: 11810032
  25. LIM kinase mediates estrogen action on the actin depolymerization factor Cofilin.
    Brain Res. 2011 Mar 16;1379:44-52 PMID: 20696146
  26. Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha.
    Endocrinology. 2003 May;144(5):2055-67 PMID: 12697714
  27. Characterization of a cerebellar granule progenitor cell line, EtC.1, and its responsiveness to 17-beta-estradiol.
    Brain Res. 2007 Dec;1186:29-40 PMID: 17980864
  28. Spatial reference memory and neocortical neurochemistry vary with the estrous cycle in C57BL/6 mice.
    Behav Neurosci. 2001 Feb;115(1):229-37 PMID: 11256446
  29. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.
    Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11162-6 PMID: 8248223
  30. Estrogen regulates the development of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus.
    J Neurosci. 2002 Apr 1;22(7):2650-9 PMID: 11923430
  31. CNS: sex steroids and SERMs.
    Ann N Y Acad Sci. 2003 Nov;997:378-88 PMID: 14644845
  32. Distribution of phosphorylated TrkB receptor in the mouse hippocampal formation depends on sex and estrous cycle stage.
    J Neurosci. 2011 May 4;31(18):6780-90 PMID: 21543608
  33. ERbeta-selective SERMs produce mnemonic-enhancing effects in the inhibitory avoidance and water maze tasks.
    Neurobiol Learn Mem. 2006 Mar;85(2):183-91 PMID: 16326119
  34. Estrogen and aging affect the subcellular distribution of estrogen receptor-alpha in the hippocampus of female rats.
    J Neurosci. 2002 May 1;22(9):3608-14 PMID: 11978836
  35. PSD-95 involvement in maturation of excitatory synapses.
    Science. 2000 Nov 17;290(5495):1364-8 PMID: 11082065
  36. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood.
    J Neurosci. 1990 Apr;10(4):1286-91 PMID: 2329377
  37. Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism.
    Neurobiol Learn Mem. 1997 Sep;68(2):172-88 PMID: 9322259
  38. 17beta-Estradiol potentiates field excitatory postsynaptic potentials within each subfield of the hippocampus with greatest potentiation of the associational/commissural afferents of CA3.
    Neuroscience. 2006 Aug 11;141(1):391-406 PMID: 16725270
  39. Membrane-initiated actions of estrogens in neuroendocrinology: emerging principles.
    Endocr Rev. 2007 Feb;28(1):1-19 PMID: 17018839
  40. Increased estrogen receptor beta expression correlates with decreased spine formation in the rat hippocampus.
    Hippocampus. 2006;16(5):453-63 PMID: 16526034
  41. Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.
    J Neurosci. 2003 Mar 15;23(6):2340-7 PMID: 12657693
  42. Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors.
    Neuroscience. 2009 Mar 3;159(1):204-16 PMID: 19150393
  43. Estrogen and aging affect synaptic distribution of phosphorylated LIM kinase (pLIMK) in CA1 region of female rat hippocampus.
    Neuroscience. 2008 Mar 18;152(2):360-70 PMID: 18294775
  44. Select estrogens within the complex formulation of conjugated equine estrogens (Premarin) are protective against neurodegenerative insults: implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer's disease.
    BMC Neurosci. 2006 Mar 13;7:24 PMID: 16533397
  45. Spine changes associated with long-term potentiation.
    Hippocampus. 2000;10(5):596-604 PMID: 11075830
  46. Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors.
    J Neurosci. 2008 Aug 27;28(35):8660-7 PMID: 18753366
  47. 17beta-estradiol modifies stress-induced and age-related changes in hippocampal synaptic plasticity.
    Behav Neurosci. 2008 Apr;122(2):301-9 PMID: 18410170
  48. Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice.
    Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2185-90 PMID: 14766964
  49. Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters.
    Horm Behav. 1998 Oct;34(2):149-62 PMID: 9799625
  50. Toward a functional neuroanatomy of premenstrual dysphoric disorder.
    J Affect Disord. 2008 May;108(1-2):87-94 PMID: 18031826
  51. The effects of cocaine on CART expression in the rat nucleus accumbens: a possible role for corticosterone.
    Eur J Pharmacol. 2005 Jul 4;517(1-2):45-50 PMID: 15972209
  52. Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines.
    Science. 2008 Mar 21;319(5870):1683-7 PMID: 18309046
  53. Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone.
    Endocrinology. 1992 Sep;131(3):1458-66 PMID: 1505477
  54. BDNF variant Val66Met interacts with estrous cycle in the control of hippocampal function.
    Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4395-400 PMID: 20142488
  55. Critical role for estrogen receptor alpha in negative feedback regulation of gonadotropin-releasing hormone mRNA expression in the female mouse.
    Neuroendocrinology. 2003 Oct;78(4):204-9 PMID: 14583652
  56. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus.
    Science. 1995 Mar 17;267(5204):1658-62 PMID: 7886457
  57. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat.
    J Neurosci. 1992 Jul;12(7):2549-54 PMID: 1613547
  58. Essential role for TrkB receptors in hippocampus-mediated learning.
    Neuron. 1999 Oct;24(2):401-14 PMID: 10571233
  59. Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats.
    Brain Res. 1997 Dec 19;778(2):430-8 PMID: 9459564
  60. Intracellular signaling pathways: nongenomic actions of estrogens and ligand-independent activation of estrogen receptors.
    Front Biosci. 2001 Oct 01;6:D1379-91 PMID: 11578956
  61. Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task.
    Neurobiol Learn Mem. 2007 Sep;88(2):208-16 PMID: 17507257
  62. Estrogen receptor beta mediates rapid estrogen actions on gonadotropin-releasing hormone neurons in vivo.
    J Neurosci. 2003 Jul 2;23(13):5771-7 PMID: 12843281
  63. Uncovering the mechanisms of estrogen effects on hippocampal function.
    Front Neuroendocrinol. 2008 May;29(2):219-37 PMID: 18078984
  64. Rapid enhancement of visual and place memory by estrogens in rats.
    Endocrinology. 2003 Jul;144(7):2836-44 PMID: 12810538
  65. A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC.
    Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19571-6 PMID: 18073185
  66. Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination.
    Neuron. 2006 May 18;50(4):549-59 PMID: 16701206
  67. LTP varies across the estrous cycle: enhanced synaptic plasticity in proestrus rats.
    Brain Res. 1995 Dec 12;703(1-2):26-30 PMID: 8719612
  68. 17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation.
    J Neurophysiol. 1999 Feb;81(2):925-9 PMID: 10036289
  69. Estrogen modulates place learning through estrogen receptors in the hippocampus.
    Neurobiol Learn Mem. 2006 Nov;86(3):336-43 PMID: 16979357
  70. Estrogen and aging affect the synaptic distribution of estrogen receptor β-immunoreactivity in the CA1 region of female rat hippocampus.
    Brain Res. 2011 Mar 16;1379:86-97 PMID: 20875808
  71. Estrogen enhances performance of female rats during acquisition of a radial arm maze.
    Horm Behav. 1997 Dec;32(3):217-25 PMID: 9454673
  72. Nuclear and extranuclear pathway inputs in the regulation of global gene expression by estrogen receptors.
    Mol Endocrinol. 2008 Sep;22(9):2116-27 PMID: 18617595
  73. Kappa opioid receptors in rat spinal cord vary across the estrous cycle.
    Brain Res. 2000 Apr 7;861(1):168-72 PMID: 10751578
  74. beta-Estradiol induces synaptogenesis in the hippocampus by enhancing brain-derived neurotrophic factor release from dentate gyrus granule cells.
    Brain Res. 2007 May 30;1150:108-20 PMID: 17433270
  75. Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line.
    Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12267-71 PMID: 11572951
  76. Cellular and subcellular localization of estrogen and progestin receptor immunoreactivities in the mouse hippocampus.
    J Comp Neurol. 2010 Jul 15;518(14):2729-43 PMID: 20506473
  77. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system.
    J Comp Neurol. 1997 Dec 1;388(4):507-25 PMID: 9388012
  78. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons.
    J Neurosci. 1990 Dec;10(12):4035-9 PMID: 2269895
  79. Critical in vivo roles for classical estrogen receptors in rapid estrogen actions on intracellular signaling in mouse brain.
    Endocrinology. 2004 Jul;145(7):3055-61 PMID: 14976146
  80. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons.
    Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):865-70 PMID: 14694190
  81. Estrogen-induced changes in place and response learning in young adult female rats.
    Behav Neurosci. 2002 Jun;116(3):411-20 PMID: 12049322
  82. Spatial and nonspatial learning across the rat estrous cycle.
    Behav Neurosci. 1997 Apr;111(2):259-66 PMID: 9106666
  83. Shifts in preferred learning strategy across the estrous cycle in female rats.
    Horm Behav. 2004 May;45(5):330-8 PMID: 15109907
  84. Hippocampal structural changes across the menstrual cycle.
    Hippocampus. 2008;18(10):985-8 PMID: 18767068
  85. Brain-derived neurotrophic factor triggers transcription-dependent, late phase long-term potentiation in vivo.
    J Neurosci. 2002 Sep 1;22(17):7453-61 PMID: 12196567
  86. Estrogens and age-related memory decline in rodents: what have we learned and where do we go from here?
    Horm Behav. 2009 Jan;55(1):2-23 PMID: 18835561
  87. Impairment of spatial learning by estradiol treatment in female mice is attenuated by estradiol exposure during development.
    Horm Behav. 2006 Dec;50(5):693-8 PMID: 16884724
  88. Hippocampal formation: shedding light on the influence of sex and stress on the brain.
    Brain Res Rev. 2007 Oct;55(2):343-55 PMID: 17395265
  89. PSD-95 is required for activity-driven synapse stabilization.
    Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4176-81 PMID: 17360496
  90. Cyclical changes in endogenous levels of oestrogen modulate the induction of LTD and LTP in the hippocampal CA1 region.
    Eur J Neurosci. 1999 Dec;11(12):4476-80 PMID: 10594677
  91. Expression of aromatase in the embryonic and postnatal mouse striatum.
    Brain Res Mol Brain Res. 1998 Dec 10;63(1):184-8 PMID: 9838103
  92. BDNF is essential to promote persistence of long-term memory storage.
    Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2711-6 PMID: 18263738
  93. Changes in hippocampal function of ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge.
    Eur J Neurosci. 2007 Nov;26(9):2595-612 PMID: 17970745
  94. Estradiol-induced object memory consolidation in middle-aged female mice requires dorsal hippocampal extracellular signal-regulated kinase and phosphatidylinositol 3-kinase activation.
    J Neurosci. 2010 Mar 24;30(12):4390-400 PMID: 20335475
  95. Estrogen enhances retrograde transport of brain-derived neurotrophic factor in the rodent forebrain.
    Endocrinology. 2003 Nov;144(11):5022-9 PMID: 12960034
  96. Estrogen receptor alpha and beta specific agonists regulate expression of synaptic proteins in rat hippocampus.
    Brain Res. 2009 Sep 22;1290:1-11 PMID: 19596275
  97. Estrogen stimulates postsynaptic density-95 rapid protein synthesis via the Akt/protein kinase B pathway.
    J Neurosci. 2003 Mar 15;23(6):2333-9 PMID: 12657692
  98. Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor.
    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11110-4 PMID: 7479947
  99. Post-training estrogen enhances spatial and object memory consolidation in female mice.
    Pharmacol Biochem Behav. 2006 May;84(1):112-9 PMID: 16759685
  100. Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: differences with the effect of estradiol.
    J Neurobiol. 2004 Nov;61(2):209-21 PMID: 15389604
  101. Estrogen and cognitive functioning in women.
    Endocr Rev. 2003 Apr;24(2):133-51 PMID: 12700177
  102. Impact of oral contraceptive pill use on premenstrual mood: predictors of improvement and deterioration.
    Am J Obstet Gynecol. 2003 Dec;189(6):1523-30 PMID: 14710055
  103. The influence of gonadal hormones on neuronal excitability, seizures, and epilepsy in the female.
    Epilepsia. 2006 Sep;47(9):1423-40 PMID: 16981857
  104. Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha.
    Mol Endocrinol. 1997 Sep;11(10):1486-96 PMID: 9280064
  105. Levels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous cycle and increase in response to acute hormone replacement.
    Brain Res. 1998 Mar 23;787(2):259-68 PMID: 9518642
  106. Extranuclear steroid receptors: nature and actions.
    Endocr Rev. 2007 Dec;28(7):726-41 PMID: 17916740
  107. Production of proinflammatory cytokines and chemokines during neuroinflammation: novel roles for estrogen receptors alpha and beta.
    Endocrinology. 2010 Oct;151(10):4916-25 PMID: 20685874
  108. Phosphatidylinositol 3-kinase is required for the expression but not for the induction or the maintenance of long-term potentiation in the hippocampal CA1 region.
    J Neurosci. 2002 May 1;22(9):3359-65 PMID: 11978812
  109. Expression of estrogen receptor (ER)-alpha and -beta immunoreactivity in hippocampal cell cultures with special attention to GABAergic neurons.
    J Neurosci Res. 2001 Sep 1;65(5):396-402 PMID: 11536322
  110. Effects of estradiol benzoate on learning-memory behavior and synaptic structure in ovariectomized mice.
    Life Sci. 2006 Sep 13;79(16):1553-60 PMID: 16750837
  111. Estrogen- and tamoxifen-associated effects on brain structure and function.
    Neuroimage. 2004 Jan;21(1):364-71 PMID: 14741674
  112. Distribution and hormone regulation of estrogen receptor immunoreactive cells in the hippocampus of male and female rats.
    J Comp Neurol. 1997 Dec 1;388(4):603-12 PMID: 9388019
  113. Regulation of dendritic spine density in cultured rat hippocampal neurons by steroid hormones.
    J Neurosci. 1996 Jul 1;16(13):4059-68 PMID: 8753868
  114. Premenstrual syndrome.
    Lancet. 2008 Apr 5;371(9619):1200-10 PMID: 18395582
  115. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.
    Science. 1995 Sep 22;269(5231):1737-40 PMID: 7569905
  116. Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: a unified mechanism of estrogen action.
    J Neurosci. 2006 Sep 13;26(37):9439-47 PMID: 16971528
  117. Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor.
    J Neurosci. 2003 Dec 17;23(37):11641-52 PMID: 14684866
  118. GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance.
    Brain Res. 2011 Mar 16;1379:53-60 PMID: 21138734
  119. Estrous cycle regulates activation of hippocampal Akt, LIM kinase, and neurotrophin receptors in C57BL/6 mice.
    Neuroscience. 2008 Sep 9;155(4):1106-19 PMID: 18601981
  120. Generation and reproductive phenotypes of mice lacking estrogen receptor beta.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15677-82 PMID: 9861029
  121. Estrogen induces phosphorylation of cyclic AMP response element binding (pCREB) in primary hippocampal cells in a time-dependent manner.
    Neuroscience. 2004;124(3):549-60 PMID: 14980726
  122. Ovariectomized rats show decreased recognition memory and spine density in the hippocampus and prefrontal cortex.
    Brain Res. 2006 Dec 18;1126(1):176-82 PMID: 16934233
  123. Variant brain-derived neurotrophic factor (Val66Met) alters adult olfactory bulb neurogenesis and spontaneous olfactory discrimination.
    J Neurosci. 2008 Mar 5;28(10):2383-93 PMID: 18322085
  124. Hippocampal synapses depend on hippocampal estrogen synthesis.
    J Neurosci. 2004 Jun 30;24(26):5913-21 PMID: 15229239
  125. Beta estrogen receptor knockout (BERKO) mice present attenuated hippocampal CA1 long-term potentiation and related memory deficits in contextual fear conditioning.
    Behav Brain Res. 2005 Oct 14;164(1):128-31 PMID: 16054246
Article Info
Journal
Neuroscience
Abbr.
Neuroscience
ISSN
1873-7544
DOI
10.1016/j.neuroscience.2011.11.035
Email
[email protected]
Published
2012-01-27
Epub
2011-00-23
Pages
131-46
Language
English
Region
United States
NLM ID
7605074
PMCID
PMC3505616
Subset
IM
Grants
NIDA NIH HHS · DA08259 · United States
NINDS NIH HHS · R01 NS007080 · United States
NIGMS NIH HHS · GM07739 · United States
NINDS NIH HHS · NS007080 · United States
NIDA NIH HHS · R01 DA008259 · United States
NIMH NIH HHS · MH082528 · United States
NIDDK NIH HHS · T32 DK007313 · United States
NIMH NIH HHS · F30 MH082528 · United States
NIA NIH HHS · P01 AG016765 · United States
NIDDK NIH HHS · DK07313 · United States
NIA NIH HHS · AG016765 · United States
NIGMS NIH HHS · T32 GM007739 · United States
External Links
PubMed source DOI: 10.1016/j.neuroscience.2011.11.035 PMC Full Text View journal details
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