Home LiteratureArticle Details
PMID: 18078984 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Uncovering the mechanisms of estrogen effects on hippocampal function.

Frontiers in neuroendocrinology ·Vol. 29 ·No. 2 ·2008-05-00 ·Pages 219-37

Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS

Abstract

Estrogens have direct effects on the brain areas controlling cognition. One of the most studied of these regions is the dorsal hippocampal formation, which governs the formation of spatial and episodic memories. In laboratory animals, most investigators report that estrogen enhances synaptic plasticity and improves performance on hippocampal-dependent cognitive behaviors. This review summarizes work conducted in our laboratory and others toward identifying estrogen's actions in the hippocampal formation, and the mechanisms for these actions. Physiologic and pharmacologic estrogen affects cognitive behavior in mammals, which may be applicable to human health and disease. The effects of estrogen in the hippocampal formation that lead to modulation of hippocampal function include effects on cell morphology, synapse formation, signaling, and excitability that have been studied in laboratory mice, rats, and primates. Finally, estrogen may signal through both nuclear and extranuclear hippocampal estrogen receptors to achieve its downstream effects.

MeSH Terms
Acetylcholine/physiology Aging/physiology Animals Calcium-Calmodulin-Dependent Protein Kinase Type 2/physiology Cognition/drug effects Cyclic AMP Response Element-Binding Protein/physiology Estradiol/pharmacology Estrogens/physiology Estrous Cycle/physiology Female Genome Hippocampus/drug effects,physiology Humans Long-Term Potentiation/drug effects,physiology Mitogen-Activated Protein Kinase Kinases/physiology Nerve Growth Factors/physiology Neurotransmitter Agents/physiology Ovariectomy Ovary/physiology Postmenopause/physiology Prefrontal Cortex/physiology Receptors, Estrogen/physiology Receptors, N-Methyl-D-Aspartate/physiology gamma-Aminobutyric Acid/physiology
Chemicals
Cyclic AMP Response Element-Binding Protein Estrogens Nerve Growth Factors Neurotransmitter Agents Receptors, Estrogen Receptors, N-Methyl-D-Aspartate Estradiol gamma-Aminobutyric Acid Calcium-Calmodulin-Dependent Protein Kinase Type 2 Mitogen-Activated Protein Kinase Kinases Acetylcholine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Spencer Joanna L
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1300 York Avenue, New York, NY 10065, USA.
Waters Elizabeth M
Romeo Russell D
Wood Gwendolyn E
Milner Teresa A
McEwen Bruce S
References (178)
178 references, click to expand
  1. A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior.
    Neuropsychopharmacology. 2006 Jun;31(6):1097-111 PMID: 16554740
  2. Estradiol's effects on learning and neuronal morphology vary with route of administration.
    Behav Neurosci. 2006 Aug;120(4):905-16 PMID: 16893296
  3. Ultrastructural localization of full-length trkB immunoreactivity in rat hippocampus suggests multiple roles in modulating activity-dependent synaptic plasticity.
    J Neurosci. 1999 Sep 15;19(18):8009-26 PMID: 10479701
  4. Interaction of rapid signal transduction cascades and gene expression in mediating estrogen effects on memory over the life span.
    Front Neuroendocrinol. 2005 Sep;26(2):51-64 PMID: 16023185
  5. 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
  6. Ovarian steroids and selective estrogen receptor modulators activity on rat brain NMDA and AMPA receptors.
    Brain Res Brain Res Rev. 2001 Nov;37(1-3):153-61 PMID: 11744083
  7. Mitogen-activated protein kinases in synaptic plasticity and memory.
    Curr Opin Neurobiol. 2004 Jun;14(3):311-7 PMID: 15194111
  8. 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
  9. Rapid stimulation of the PI3-kinase/Akt signalling pathway in developing midbrain neurones by oestrogen.
    J Neuroendocrinol. 2002 Jan;14(1):73-9 PMID: 11903815
  10. Synapse-specific regulation of AMPA receptor function by PSD-95.
    Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19535-40 PMID: 17148601
  11. Associative memory formation increases the observation of dendritic spines in the hippocampus.
    J Neurosci. 2003 Jan 15;23(2):659-65 PMID: 12533625
  12. 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
  13. Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA receptor-mediated synaptic input: correlation with dendritic spine density.
    J Neurosci. 1997 Mar 1;17(5):1848-59 PMID: 9030643
  14. 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
  15. Spatial memory retention is enhanced by acute and continuous estradiol replacement.
    Horm Behav. 2004 Feb;45(2):128-35 PMID: 15019800
  16. Spine-type densities of hippocampal CA1 neurons vary in proestrus and estrus rats.
    Neurosci Lett. 2005 Apr 29;379(1):52-4 PMID: 15814198
  17. Sex differences in hippocampal estradiol-induced N-methyl-D-aspartic acid binding and ultrastructural localization of estrogen receptor-alpha.
    Neuroendocrinology. 2005;81(6):391-9 PMID: 16276117
  18. Learning induces long-term potentiation in the hippocampus.
    Science. 2006 Aug 25;313(5790):1093-7 PMID: 16931756
  19. Neurotrophic factors and estradiol interact to control axogenic growth in hypothalamic neurons.
    Ann N Y Acad Sci. 2003 Dec;1007:306-16 PMID: 14993063
  20. Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation.
    Endocrinology. 2006 Jan;147(1):607-14 PMID: 16239296
  21. Intra-hippocampal estradiol infusion enhances memory in ovariectomized rats.
    Neuroreport. 1997 Sep 29;8(14):3009-13 PMID: 9331907
  22. Tamoxifen enhances choline acetyltransferase mRNA expression in rat basal forebrain cholinergic neurons.
    Brain Res Mol Brain Res. 2002 Jun 30;103(1-2):140-5 PMID: 12106699
  23. Glutamic acid decarboxylase messenger ribonucleic acid is regulated by estradiol and progesterone in the hippocampus.
    Endocrinology. 1992 Dec;131(6):2697-702 PMID: 1446611
  24. Novel effects of estradiol and estrogen receptor alpha and beta on cognitive function.
    Brain Res. 2000 Nov 17;883(2):258-64 PMID: 11074057
  25. Autoradiographic localization of estradiol-binding neurons in the rat hippocampal formation and entorhinal cortex.
    Brain Res. 1988 Apr 1;467(2):245-51 PMID: 3378173
  26. Estradiol affects spinophilin protein differently in gonadectomized males and females.
    Neuroscience. 2004;127(4):983-8 PMID: 15312910
  27. Integration of the extranuclear and nuclear actions of estrogen.
    Mol Endocrinol. 2005 Aug;19(8):1951-9 PMID: 15705661
  28. 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
  29. Changes in interneuronal phenotypes regulated by estradiol in the adult rat hippocampus: a potential role for neuropeptide Y.
    Neuroscience. 2005;136(1):357-69 PMID: 16198490
  30. Investigative models for determining hormone therapy-induced outcomes in brain: evidence in support of a healthy cell bias of estrogen action.
    Ann N Y Acad Sci. 2005 Jun;1052:57-74 PMID: 16024751
  31. Ultrastructural evidence for mu-opioid modulation of cholinergic pathways in rat dentate gyrus.
    Brain Res. 2004 Sep 3;1019(1-2):28-38 PMID: 15306235
  32. Estrogen activation of cyclic adenosine 5'-monophosphate response element-mediated transcription requires the extracellularly regulated kinase/mitogen-activated protein kinase pathway.
    Endocrinology. 2003 Mar;144(3):832-8 PMID: 12586759
  33. Differential effects of estrogen on hippocampal- and striatal-dependent learning.
    Neurobiol Learn Mem. 2005 Sep;84(2):132-7 PMID: 16054404
  34. Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats.
    J Neurobiol. 2003 May;55(2):247-60 PMID: 12672021
  35. The effect of different doses of micronized 17beta-estradiol on C-reactive protein, interleukin-6, and lipids in older women.
    J Gerontol A Biol Sci Med Sci. 2004 Aug;59(8):827-32 PMID: 15345733
  36. Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: complexity of steroid hormone-growth factor interactions in the adult CNS.
    Front Neuroendocrinol. 2006 Dec;27(4):415-35 PMID: 17055560
  37. Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha.
    Endocrinology. 2003 May;144(5):2055-67 PMID: 12697714
  38. Raloxifene and estradiol benzoate both fully restore hippocampal choline acetyltransferase activity in ovariectomized rats.
    Brain Res. 1999 Nov 13;847(1):98-104 PMID: 10564741
  39. 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
  40. Inhibition of tyrosine kinase receptor type B synthesis blocks axogenic effect of estradiol on rat hypothalamic neurones in vitro.
    Eur J Neurosci. 2004 Jul;20(2):331-7 PMID: 15233742
  41. Estrogenic agonist activity of ICI 182,780 (Faslodex) in hippocampal neurons: implications for basic science understanding of estrogen signaling and development of estrogen modulators with a dual therapeutic profile.
    J Pharmacol Exp Ther. 2006 Dec;319(3):1124-32 PMID: 16951259
  42. Non-nuclear estrogen receptor beta and alpha in the hippocampus of male and female rats.
    Hippocampus. 2005;15(3):404-12 PMID: 15669092
  43. Dose and temporal pattern of estrogen exposure determines neuroprotective outcome in hippocampal neurons: therapeutic implications.
    Endocrinology. 2006 Nov;147(11):5303-13 PMID: 16916950
  44. Estrogen regulation of mu-opioid receptor mRNA in the forebrain of female rats.
    Brain Res Mol Brain Res. 1997 Jul;47(1-2):134-8 PMID: 9221910
  45. Effects of estrogen treatment on expression of brain-derived neurotrophic factor and cAMP response element-binding protein expression and phosphorylation in rat amygdaloid and hippocampal structures.
    Neuroendocrinology. 2005;81(5):294-310 PMID: 16179807
  46. Acetylcholine mediates the estrogen-induced increase in NMDA receptor binding in CA1 of the hippocampus and the associated improvement in working memory.
    J Neurosci. 2001 Sep 1;21(17):6949-56 PMID: 11517282
  47. PSD-95 involvement in maturation of excitatory synapses.
    Science. 2000 Nov 17;290(5495):1364-8 PMID: 11082065
  48. Rapid modulation of long-term depression and spinogenesis via synaptic estrogen receptors in hippocampal principal neurons.
    J Neurochem. 2007 Feb;100(4):950-67 PMID: 17266735
  49. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood.
    J Neurosci. 1990 Apr;10(4):1286-91 PMID: 2329377
  50. Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein.
    Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1482-7 PMID: 9037079
  51. 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
  52. Prefrontal cortex as the site of estrogen's effect on cognition.
    Psychoneuroendocrinology. 2001 Aug;26(6):577-90 PMID: 11403979
  53. Postsynaptic TrkB signaling has distinct roles in spine maintenance in adult visual cortex and hippocampus.
    Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1071-6 PMID: 16418274
  54. "Add-back" estrogen reverses cognitive deficits induced by a gonadotropin-releasing hormone agonist in women with leiomyomata uteri.
    J Clin Endocrinol Metab. 1996 Jul;81(7):2545-9 PMID: 8675575
  55. 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 Nov 9;810(1-2):294 PMID: 9813376
  56. Characterization of the ovariectomized rat model for the evaluation of estrogen effects on plasma cholesterol levels.
    Endocrinology. 1997 Apr;138(4):1552-8 PMID: 9075715
  57. Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism.
    Neurobiol Learn Mem. 1997 Sep;68(2):172-88 PMID: 9322259
  58. Distinctive features of Trk neurotrophin receptor transactivation by G protein-coupled receptors.
    Cytokine Growth Factor Rev. 2002 Feb;13(1):11-7 PMID: 11750876
  59. 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
  60. Membrane-initiated actions of estrogens in neuroendocrinology: emerging principles.
    Endocr Rev. 2007 Feb;28(1):1-19 PMID: 17018839
  61. Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.
    J Neurosci. 2003 Mar 15;23(6):2340-7 PMID: 12657693
  62. Increased estrogen receptor beta expression correlates with decreased spine formation in the rat hippocampus.
    Hippocampus. 2006;16(5):453-63 PMID: 16526034
  63. Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women.
    Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8836-41 PMID: 9238064
  64. 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
  65. 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
  66. 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
  67. BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development.
    J Neurosci. 2004 Aug 18;24(33):7366-77 PMID: 15317862
  68. Differential regulation of NMDAR1 mRNA and protein by estradiol in the rat hippocampus.
    J Neurosci. 1996 Nov 1;16(21):6830-8 PMID: 8824322
  69. Estradiol selectively regulates agonist binding sites on the N-methyl-D-aspartate receptor complex in the CA1 region of the hippocampus.
    Endocrinology. 1992 Aug;131(2):662-8 PMID: 1353442
  70. Biochemical mechanisms for translational regulation in synaptic plasticity.
    Nat Rev Neurosci. 2004 Dec;5(12):931-42 PMID: 15550948
  71. Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor-dependent mechanism.
    J Neurosci. 1994 Dec;14(12):7680-7 PMID: 7996203
  72. Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice.
    Neuron. 2002 Jul 3;35(1):121-33 PMID: 12123613
  73. Neurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation.
    Neurobiol Aging. 2001 Mar-Apr;22(2):309-19 PMID: 11182481
  74. Hormone therapy and cognitive function: is there a critical period for benefit?
    Neuroscience. 2006;138(3):1027-30 PMID: 16488547
  75. Effects of steroids on the brain opioid system.
    J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):343-8 PMID: 7626478
  76. 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
  77. Inhibition of dendritic spine induction on hippocampal CA1 pyramidal neurons by a nonsteroidal estrogen antagonist in female rats.
    Endocrinology. 1999 Mar;140(3):1044-7 PMID: 10067823
  78. 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.
    Exp Neurol. 1994 Sep;129(1):70-80 PMID: 7925844
  79. Similarities between actions of estrogen and BDNF in the hippocampus: coincidence or clue?
    Trends Neurosci. 2005 Feb;28(2):79-85 PMID: 15667930
  80. ER-X: a novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury.
    J Neurosci. 2002 Oct 1;22(19):8391-401 PMID: 12351713
  81. Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats.
    Brain Res. 1997 Dec 19;778(2):430-8 PMID: 9459564
  82. Estrogen-BDNF interactions: implications for neurodegenerative diseases.
    Front Neuroendocrinol. 2006 Dec;27(4):404-14 PMID: 17069877
  83. Thinking outside the pyramidal cell: unexplored contributions of interneurons and neuropeptide Y to estrogen-induced synapse formation in the hippocampus.
    Rev Neurosci. 2007;18(1):1-13 PMID: 17405448
  84. Rapid enhancement of visual and place memory by estrogens in rats.
    Endocrinology. 2003 Jul;144(7):2836-44 PMID: 12810538
  85. Spinophilin is phosphorylated by Ca2+/calmodulin-dependent protein kinase II resulting in regulation of its binding to F-actin.
    J Neurochem. 2004 Jul;90(2):317-24 PMID: 15228588
  86. The Women's Health Initiative Memory Study: findings and implications for treatment.
    Lancet Neurol. 2005 Mar;4(3):190-4 PMID: 15721829
  87. LTP varies across the estrous cycle: enhanced synaptic plasticity in proestrus rats.
    Brain Res. 1995 Dec 12;703(1-2):26-30 PMID: 8719612
  88. Estrogen modulates place learning through estrogen receptors in the hippocampus.
    Neurobiol Learn Mem. 2006 Nov;86(3):336-43 PMID: 16979357
  89. Role of estrogen in balancing contributions from multiple memory systems.
    Neurobiol Learn Mem. 2004 Nov;82(3):309-23 PMID: 15464412
  90. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.
    JAMA. 2003 May 28;289(20):2651-62 PMID: 12771112
  91. Estrogen enhances performance of female rats during acquisition of a radial arm maze.
    Horm Behav. 1997 Dec;32(3):217-25 PMID: 9454673
  92. 17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation.
    J Neurophysiol. 1999 Feb;81(2):925-9 PMID: 10036289
  93. Estrogen regulates functional inhibition of hippocampal CA1 pyramidal cells in the adult female rat.
    J Neurosci. 2001 Sep 1;21(17):6532-43 PMID: 11517242
  94. Estrogen-like activity of tamoxifen and raloxifene on NMDA receptor binding and expression of its subunits in rat brain.
    Neuropsychopharmacology. 2001 Aug;25(2):242-57 PMID: 11425508
  95. Dendritic spine morphogenesis and plasticity.
    J Neurobiol. 2005 Jul;64(1):47-57 PMID: 15884005
  96. Hippocampal tyrosine kinase A receptors are restricted primarily to presynaptic vesicle clusters.
    J Comp Neurol. 2001 Feb 5;430(2):182-99 PMID: 11135255
  97. A role for the basal forebrain cholinergic system in estrogen-induced disinhibition of hippocampal pyramidal cells.
    J Neurosci. 2003 Jun 1;23(11):4479-90 PMID: 12805288
  98. The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats.
    Endocrinology. 2005 Jan;146(1):287-93 PMID: 15486220
  99. Estradiol increases spine density and NMDA-dependent Ca2+ transients in spines of CA1 pyramidal neurons from hippocampal slices.
    J Neurophysiol. 1999 Mar;81(3):1404-11 PMID: 10085365
  100. 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
  101. Cholinergic septal afferent terminals preferentially contact neuropeptide Y-containing interneurons compared to parvalbumin-containing interneurons in the rat dentate gyrus.
    J Neurosci. 1999 Nov 15;19(22):10140-52 PMID: 10559422
  102. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons.
    J Neurosci. 1990 Dec;10(12):4035-9 PMID: 2269895
  103. Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys.
    J Neurosci. 2003 Jul 2;23(13):5708-14 PMID: 12843274
  104. Estrogen induces estrogen receptor alpha-dependent cAMP response element-binding protein phosphorylation via mitogen activated protein kinase pathway in basal forebrain cholinergic neurons in vivo.
    J Neurosci. 2006 Apr 12;26(15):4104-10 PMID: 16611827
  105. Estradiol increases dendritic spine density by reducing GABA neurotransmission in hippocampal neurons.
    J Neurosci. 1998 Apr 1;18(7):2550-9 PMID: 9502814
  106. Estrogen mobilizes a subset of estrogen receptor-alpha-immunoreactive vesicles in inhibitory presynaptic boutons in hippocampal CA1.
    J Neurosci. 2007 Feb 21;27(8):2102-11 PMID: 17314305
  107. Effect of gonadal steroids on activities of monoamine oxidase and choline acetylase in rat brain.
    Brain Res. 1975 Mar 21;86(2):293-306 PMID: 1115999
  108. Estrogen-induced changes in place and response learning in young adult female rats.
    Behav Neurosci. 2002 Jun;116(3):411-20 PMID: 12049322
  109. Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions.
    Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6013-8 PMID: 17389368
  110. Localization of estrogen receptor beta-immunoreactivity in astrocytes of the adult rat brain.
    Glia. 1999 May;26(3):260-7 PMID: 10340766
  111. Estrogen-containing hormone therapy and Alzheimer's disease risk: understanding discrepant inferences from observational and experimental research.
    Neuroscience. 2006;138(3):1031-9 PMID: 16310963
  112. Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys.
    J Comp Neurol. 2003 Oct 27;465(4):540-50 PMID: 12975814
  113. Shifts in preferred learning strategy across the estrous cycle in female rats.
    Horm Behav. 2004 May;45(5):330-8 PMID: 15109907
  114. Opioid systems in the dentate gyrus.
    Prog Brain Res. 2007;163:245-63 PMID: 17765723
  115. Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism.
    Neuron. 1998 Apr;20(4):709-26 PMID: 9581763
  116. Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning.
    Neurobiol Learn Mem. 2003 Nov;80(3):315-22 PMID: 14521873
  117. Gonadal hormone modulation of hippocampal neurogenesis in the adult.
    Hippocampus. 2006;16(3):225-32 PMID: 16411182
  118. Estrogen and cognitive aging in women.
    Neuroscience. 2006;138(3):1021-6 PMID: 16310965
  119. 17Beta-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. 2005;135(1):59-72 PMID: 16084662
  120. Evidence for novel estrogen binding sites in the rat hippocampus.
    Neuroscience. 2000;99(4):605-12 PMID: 10974424
  121. 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
  122. Estrogen binding and estrogen receptor characterization (ERalpha and ERbeta) in the cholinergic neurons of the rat basal forebrain.
    Neuroscience. 2000;96(1):41-9 PMID: 10683408
  123. When is a sex difference not a sex difference?
    Front Neuroendocrinol. 2005 Sep;26(2):85-102 PMID: 16083951
  124. 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
  125. Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats.
    Neurobiol Aging. 2000 Jan-Feb;21(1):107-16 PMID: 10794855
  126. Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats.
    J Neurosci. 2002 Dec 15;22(24):10985-95 PMID: 12486194
  127. Electrical activity during the estrous cycle of the rat: cyclic changes in limbic structures.
    Endocrinology. 1968 Aug;83(2):207-16 PMID: 4874282
  128. 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
  129. Virtual and biomolecular screening converge on a selective agonist for GPR30.
    Nat Chem Biol. 2006 Apr;2(4):207-12 PMID: 16520733
  130. Estrogen is more than just a "sex hormone": novel sites for estrogen action in the hippocampus and cerebral cortex.
    Front Neuroendocrinol. 2000 Jan;21(1):95-101 PMID: 10662537
  131. Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats.
    Neuroscience. 2006 Sep 15;141(4):1793-800 PMID: 16797852
  132. Chronic oral estrogen affects memory and neurochemistry in middle-aged female mice.
    Behav Neurosci. 2004 Dec;118(6):1340-51 PMID: 15598143
  133. Involvement of BDNF receptor TrkB in spatial memory formation.
    Learn Mem. 2003 Mar-Apr;10(2):108-15 PMID: 12663749
  134. Effects of an estrogen antagonist on enzyme activities and [3H]estradiol nuclear binding in uterus, pituitary and brain.
    Endocrinology. 1977 Apr;100(4):903-10 PMID: 837886
  135. 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
  136. Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling.
    Nat Neurosci. 2003 Feb;6(2):153-60 PMID: 12496762
  137. Nature of functional estrogen receptors at the plasma membrane.
    Mol Endocrinol. 2006 Sep;20(9):1996-2009 PMID: 16645038
  138. Astrocytic volume fluctuates in the hippocampal CA1 region across the estrous cycle.
    Brain Res. 1995 Sep 4;690(2):269-74 PMID: 8535849
  139. TrkA immunoreactive astrocytes in dendritic fields of the hippocampal formation across estrous.
    Glia. 2002 Apr 1;38(1):36-44 PMID: 11921202
  140. Is there a link between adult neurogenesis and learning?
    Hippocampus. 2006;16(3):216-24 PMID: 16421862
  141. 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
  142. Subcellular relationships between cholinergic terminals and estrogen receptor-alpha in the dorsal hippocampus.
    J Comp Neurol. 2003 Sep 1;463(4):390-401 PMID: 12836175
  143. Gender and endogenous levels of estradiol do not influence adult hippocampal neurogenesis in mice.
    Hippocampus. 2007;17(3):175-80 PMID: 17286277
  144. Estrogen and cognitive functioning in women.
    Endocr Rev. 2003 Apr;24(2):133-51 PMID: 12700177
  145. Spinophilin regulates the formation and function of dendritic spines.
    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9287-92 PMID: 10922077
  146. Estradiol enhances neurogenesis in the dentate gyri of adult male meadow voles by increasing the survival of young granule neurons.
    Neuroscience. 2004;128(3):645-54 PMID: 15381292
  147. The influence of gonadal hormones on neuronal excitability, seizures, and epilepsy in the female.
    Epilepsia. 2006 Sep;47(9):1423-40 PMID: 16981857
  148. Mechanisms of neuroprotection by estrogen.
    Endocrine. 2006 Apr;29(2):209-15 PMID: 16785597
  149. Verbal and spatial functions across the menstrual cycle in healthy young women.
    Psychoneuroendocrinology. 2002 Oct;27(7):835-41 PMID: 12183218
  150. Rapid estrogen-induced phosphorylation of the SRC-3 coactivator occurs in an extranuclear complex containing estrogen receptor.
    Mol Cell Biol. 2005 Sep;25(18):8273-84 PMID: 16135815
  151. Glia mediates the neuroprotective action of estradiol on beta-amyloid-induced neuronal death.
    Endocrinology. 2004 Nov;145(11):5080-6 PMID: 15308615
  152. Molecular mechanisms of dendritic spine morphogenesis.
    Curr Opin Neurobiol. 2006 Feb;16(1):95-101 PMID: 16361095
  153. 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
  154. 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
  155. Regulation of dendritic spine density in cultured rat hippocampal neurons by steroid hormones.
    J Neurosci. 1996 Jul 1;16(13):4059-68 PMID: 8753868
  156. Novel target sites for estrogen action in the dorsal hippocampus: an examination of synaptic proteins.
    Endocrinology. 2001 Mar;142(3):1284-9 PMID: 11181546
  157. Both estrogen and raloxifene protect against beta-amyloid-induced neurotoxicity in estrogen receptor alpha-transfected PC12 cells by activation of telomerase activity via Akt cascade.
    J Endocrinol. 2004 Dec;183(3):605-15 PMID: 15590986
  158. 17beta-estradiol induces Ca2+ influx, dendritic and nuclear Ca2+ rise and subsequent cyclic AMP response element-binding protein activation in hippocampal neurons: a potential initiation mechanism for estrogen neurotrophism.
    Neuroscience. 2005;132(2):299-311 PMID: 15802184
  159. Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites.
    J Comp Neurol. 2001 Jan 15;429(3):355-71 PMID: 11116225
  160. Neurotrophins and their receptors: a convergence point for many signalling pathways.
    Nat Rev Neurosci. 2003 Apr;4(4):299-309 PMID: 12671646
  161. Estradiol, but not raloxifene, improves aspects of spatial working memory in aged ovariectomized rhesus monkeys.
    Neurobiol Aging. 2002 Jul-Aug;23(4):589-600 PMID: 12009508
  162. 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
  163. Estradiol increases pre- and post-synaptic proteins in the CA1 region of the hippocampus in female rhesus macaques (Macaca mulatta).
    Endocrinology. 2003 Nov;144(11):4734-8 PMID: 12960039
  164. Estrogen induces a rapid increase of calcium-calmodulin-dependent protein kinase II activity in the hippocampus.
    Brain Res. 2002 Sep 20;950(1-2):308-11 PMID: 12231258
  165. 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
  166. 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
  167. Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat.
    Psychoneuroendocrinology. 2004 Jul;29(6):741-8 PMID: 15110923
  168. Estradiol increases the frequency of multiple synapse boutons in the hippocampal CA1 region of the adult female rat.
    J Comp Neurol. 1996 Sep 09;373(1):108-17 PMID: 8876466
  169. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.
    JAMA. 2003 May 28;289(20):2663-72 PMID: 12771113
  170. 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
  171. Protein phosphatases and calcium/calmodulin-dependent protein kinase II-dependent synaptic plasticity.
    J Neurosci. 2004 Sep 29;24(39):8404-9 PMID: 15456812
  172. Evidence that disinhibition is associated with a decrease in number of vesicles available for release at inhibitory synapses.
    J Neurosci. 2005 Jan 26;25(4):971-6 PMID: 15673678
  173. Menstrual cycle phase modulates reward-related neural function in women.
    Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2465-70 PMID: 17267613
  174. 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
  175. Mechanism of TrkB-mediated hippocampal long-term potentiation.
    Neuron. 2002 Sep 26;36(1):121-37 PMID: 12367511
  176. Effects of estrogen on basal forebrain cholinergic neurons vary as a function of dose and duration of treatment.
    Brain Res. 1997 May 16;757(1):10-6 PMID: 9200493
  177. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications.
    Steroids. 2007 May;72(5):381-405 PMID: 17379265
  178. Ultrastructural localization of estrogen receptor beta immunoreactivity in the rat hippocampal formation.
    J Comp Neurol. 2005 Oct 17;491(2):81-95 PMID: 16127691
Article Info
Journal
Frontiers in neuroendocrinology
Abbr.
Front Neuroendocrinol
ISSN
1095-6808
DOI
10.1016/j.yfrne.2007.08.006
Published
2008-05-00
Epub
2007-00-15
Pages
219-37
Language
English
Region
United States
NLM ID
7513292
PMCID
PMC2440702
Subset
IM
Grants
NHLBI NIH HHS · HL18974 · United States
NINDS NIH HHS · R01 NS007080 · United States
NINDS NIH HHS · NS 007080 · United States
NIA NIH HHS · P01 AG016765-090001 · United States
NIDA NIH HHS · R01 DA008259 · United States
NHLBI NIH HHS · P01 HL018974 · United States
NIDA NIH HHS · DA 08259 · United States
NINDS NIH HHS · R01 NS007080-41 · United States
NIA NIH HHS · P01 AG016765 · United States
NIGMS NIH HHS · T32 GM007739 · United States
External Links
PubMed source DOI: 10.1016/j.yfrne.2007.08.006 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2