Periodic Estrogen Receptor-Beta Activation: A Novel Approach to Prevent Ischemic Brain Damage

Neurochemical Research

Volumn 40, Issue 10, 2014, Pages 2009-2017

  Cue, Lauren ^a   Diaz, Francisca ^a   Briegel, Karoline J ^b   Patel, Hersila H ^a   Raval, Ami P ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MIAMI   (United States)

Author keywords

Complex IV; Estrogen; Hippocampus; Mammary gland; Mitochondria; Neuroprotection; Women

Indexed keywords

CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE; COMPLEMENTARY RNA; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; ESTROGEN; NEUROPROTECTIVE AGENT;

AGING; AMNESIA; BRAIN BLOOD VESSEL; BRAIN DAMAGE; BRAIN FUNCTION; BRAIN ISCHEMIA; DRUG MECHANISM; ENZYME ACTIVATION; ESTROGEN THERAPY; FEMALE; HIPPOCAMPUS; INTRACELLULAR SIGNALING; ISCHEMIC BRAIN DAMAGE; LEARNING DISORDER; LONG TERM MEMORY; NEUROPROTECTION; NONHUMAN; PRIMARY PREVENTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; TRANSLATIONAL RESEARCH; ANIMAL; BRAIN; BRAIN DAMAGE, CHRONIC; DRUG EFFECTS; HUMAN; METABOLISM;

ANIMALS; BRAIN; BRAIN DAMAGE, CHRONIC; BRAIN ISCHEMIA; ESTROGEN RECEPTOR BETA; ESTROGENS; HUMANS; NEUROPROTECTIVE AGENTS;

EID: 84946496302     PISSN: 03643190     EISSN: 15736903     Source Type: Journal    
DOI: 10.1007/s11064-014-1346-7     Document Type: Review

References (97)

1. Alkayed NJ, Harukuni I, Kimes AS, London ED, Traystman RJ, Hurn PD (1998) Gender-linked brain injury in experimental stroke. Stroke 29:159–165; discussion 166
2. Alkayed NJ, Murphy SJ, Traystman RJ, Hurn PD, Miller VM (2000) Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke 31:161–168
3. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O’Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 291:1701–1712
4. Arimoto JM, Wong A, Rozovsky I, Lin SW, Morgan TE, Finch CE (2013) Age increase of estrogen receptor-α (ERα) in cortical astrocytes impairs neurotrophic support in male and female rats. Endocrinology 154:2101–2113
5. Bath PM, Gray LJ (2005) Association between hormone replacement therapy and subsequent stroke: a meta-analysis. BMJ 330:342
6. Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39
7. Boulware MI, Weick JP, Becklund BR, Kuo SP, Groth RD, Mermelstein PG (2005) Estradiol activates group I and II metabotropic glutamate receptor signaling, leading to opposing influences on cAMP response element-binding protein. J Neurosci 25:5066–5078
8. Bramlett HM (2005) Sex differences and the effect of hormonal therapy on ischemic brain injury. Pathophysiology 12:17–27
9. Brinton RD (2009) Estrogen-induced plasticity from cells to circuits: predictions for cognitive function. Trends Pharmacol Sci 30:212–222
10. Cardinaux JR, Notis JC, Zhang Q, Vo N, Craig JC, Fass DM, Brennan RG, Goodman RH (2000) Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation. Mol Cell Biol 20:1546–1552
11. Carswell HV, Macrae IM, Gallagher L, Harrop E, Horsburgh KJ (2004) Neuroprotection by a selective estrogen receptor beta agonist in a mouse model of global ischemia. Am J Physiol Heart Circ Physiol 287:H1501–H1504
12. Chan PH (2004) Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res 29:1943–1949
13. Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855–859
14. Cramer DW, Harlow BL, Xu H, Fraer C, Barbieri R (1995) Cross-sectional and case-controlled analyses of the association between smoking and early menopause. Maturitas 22:79–87
15. Dai X, Chen L, Sokabe M (2007) Neurosteroid estradiol rescues ischemia-induced deficit in the long-term potentiation of rat hippocampal CA1 neurons. Neuropharmacology 52:1124–1138
16. De Rasmo D, Signorile A, Papa F, Roca E, Papa S (2010) cAMP/Ca2+ response element-binding protein plays a central role in the biogenesis of respiratory chain proteins in mammalian cells. IUBMB Life 62:447–452
17. del Zoppo GJ (2006) Stroke and neurovascular protection. N Engl J Med 354:553–555
18. Diaz F, Moraes CT (2008) Mitochondrial biogenesis and turnover. Cell Calcium 44:24–35
19. Dubal DB, Kashon ML, Pettigrew LC, Ren JM, Finklestein SP, Rau SW, Wise PM (1998) Estradiol protects against ischemic injury. J Cereb Blood Flow Metab 18:1253–1258
20. Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal SB, Merchanthaler I, Kindy MS, Wise PM (2006) Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death. Endocrinology 147:3076–3084
21. Duckles SP, Krause DN, Stirone C, Procaccio V (2006) Estrogen and mitochondria: a new paradigm for vascular protection? Mol Interv 6:26–35
22. Edwards BJ, Li J (2013) Endocrinology of menopause. Periodontology 2000(61):177–194
23. Finkbeiner S (2000) Calcium regulation of the brain-derived neurotrophic factor gene. Cell Mol Life Sci 57:394–401
24. Finkbeiner S (2000) CREB couples neurotrophin signals to survival messages. Neuron 25:11–14
25. Frasor J, Barnett DH, Danes JM, Hess R, Parlow AF, Katzenellenbogen BS (2003) Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) alpha activity by ERbeta in the uterus. Endocrinology 144:3159–3166
26. Frasor J, Danes JM, Komm B, Chang KC, Lyttle CR, Katzenellenbogen BS (2003) Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype. Endocrinology 144:4562–4574
27. Gibson CL, Gray LJ, Murphy SP, Bath PM (2006) Estrogens and experimental ischemic stroke: a systematic review. J Cereb Blood Flow Metab 26:1103–1113
28. Gulinello M, Lebesgue D, Jover-Mengual T, Zukin RS, Etgen AM (2006) Acute and chronic estradiol treatments reduce memory deficits induced by transient global ischemia in female rats. Horm Behav 49:246–260
29. Guo J, Duckles SP, Weiss JH, Li X, Krause DN (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
30. Guo J, Krause DN, Horne J, Weiss JH, Li X, Duckles SP (2010) Estrogen-receptor-mediated protection of cerebral endothelial cell viability and mitochondrial function after ischemic insult in vitro. J Cereb Blood Flow Metab 30:545–554
31. Guo S, Lo EH (2009) Dysfunctional cell–cell signaling in the neurovascular unit as a paradigm for central nervous system disease. Stroke 40:S4–S7
32. Han X, Aenlle KK, Bean LA, Rani A, Semple-Rowland SL, Kumar A, Foster TC (2013) Role of estrogen receptor alpha and beta in preserving hippocampal function during aging. J Neurosci 33:2671–2683
33. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, Tujague M, Strom A, Treuter E, Warner M, Gustafsson JA (2007) Estrogen receptors: how do they signal and what are their targets. Physiol Rev 87:905–931
34. Helguero LA, Faulds MH, Gustafsson JA, Haldosen LA (2005) Estrogen receptors alfa (ERalpha) and beta (ERbeta) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11. Oncogene 24:6605–6616
35. Higaki S, Takumi K, Itoh M, Watanabe G, Taya K, Shimizu K, Hayashi M, Oishi T (2012) Response of ERbeta and aromatase expression in the monkey hippocampal formation to ovariectomy and menopause. Neurosci Res 72:148–154
36. Hotchkiss J, Knobil E (1994) The Physiology of reproduction. Physiol Reprod 2:711–749
37. Hu BR, Fux CM, Martone ME, Zivin JA, Ellisman MH (1999) Persistent phosphorylation of cyclic AMP responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain. Neuroscience 89:437–452
38. Jensen J, Christiansen C, Rodbro P (1985) Cigarette smoking, serum estrogens, and bone loss during hormone-replacement therapy early after menopause. N Engl J Med 313:973–975
39. Jover-Mengual T, Zukin RS, Etgen AM (2007) MAPK signaling is critical to estradiol protection of CA1 neurons in global ischemia. Endocrinology 148:1131–1143. doi:10.1210/en.2006-1137
40. Jover T, Tanaka H, Calderone A, Oguro K, Bennett MV, Etgen AM, Zukin RS (2002) Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1. J Neurosci 22:2115–2124
41. Kelly MJ, Levin ER (2001) Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab 12:152–156
42. Kernan WN, Brass LM, Viscoli CM, Sarrel PM, Makuch R, Horwitz RI (1998) Estrogen after ischemic stroke: clinical basis and design of The Women’s Estrogen for Stroke Trial. J Stroke Cerebrovasc Dis 7:85–95
43. Kofler J, Hurn PD, Traystman RJ (2005) SOD1 overexpression and female sex exhibit region-specific neuroprotection after global cerebral ischemia due to cardiac arrest. J Cereb Blood Flow Metab 25:1130–1137
44. Kristian T (2004) Metabolic stages, mitochondria and calcium in hypoxic/ischemic brain damage. Cell Calcium 36:221–233
45. Lebesgue D, Chevaleyre V, Zukin RS, Etgen AM (2009) Estradiol rescues neurons from global ischemia-induced cell death: multiple cellular pathways of neuroprotection. Steroids 74:555–561
46. LeBlanc ES, Viscoli CM, Henrich JB (1999) Postmenopausal estrogen replacement therapy is associated with adverse breast cancer prognostic indices. J Womens Health Gend Based Med 8:815–823
47. Lee J, Kim CH, Simon DK, Aminova LR, Andreyev AY, Kushnareva YE, Murphy AN, Lonze BE, Kim KS, Ginty DD, Ferrante RJ, Ryu H, Ratan RR (2005) Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J Biol Chem 280:40398–40401
48. Lee SJ, Campomanes CR, Sikat PT, Greenfield AT, Allen PB, McEwen BS (2004) Estrogen induces phosphorylation of cyclic AMP response element binding (pCREB) in primary hippocampal cells in a time-dependent manner. Neuroscience 124:549–560
49. Liu F, Day M, Muniz LC, Bitran D, Arias R, Revilla-Sanchez R, Grauer S, Zhang G, Kelley C, Pulito V, Sung A, Mervis RF, Navarra R, Hirst WD, Reinhart PH, Marquis KL, Moss SJ, Pangalos MN, Brandon NJ (2008) Activation of estrogen receptor-beta regulates hippocampal synaptic plasticity and improves memory. Nat Neurosci 11:334–343. doi:10.1038/nn2057
50. Mabuchi T, Kitagawa K, Kuwabara K, Takasawa K, Ohtsuki T, Xia Z, Storm D, Yanagihara T, Hori M, Matsumoto M (2001) Phosphorylation of cAMP response element-binding protein in hippocampal neurons as a protective response after exposure to glutamate in vitro and ischemia in vivo. J Neurosci 21:9204–9213
51. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, Anderson G, Howard BV, Thomson CA, Lacroix AZ, Wactawski-Wende J, Jackson RD, Limacher M, Margolis KL, Wassertheil-Smoller S, Beresford SA, Cauley JA, Eaton CB, Gass M, Hsia J, Johnson KC, Kooperberg C, Kuller LH, Lewis CE, Liu S, Martin LW, Ockene JK, O’Sullivan MJ, Powell LH, Simon MS, Van Horn L, Vitolins MZ, Wallace RB (2013) Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 310:1353–1368
52. McEwen B, Akama K, Alves S, Brake WG, Bulloch K, Lee S, Li C, Yuen G, Milner TA (2001) Tracking the estrogen receptor in neurons: implications for estrogen-induced synapse formation. Proc Natl Acad Sci USA 98:7093–7100
53. Miller NR, Jover T, Cohen HW, Zukin RS, Etgen AM (2005) Estrogen can act via estrogen receptor alpha and beta to protect hippocampal neurons against global ischemia-induced cell death. Endocrinology 146:3070–3079
54. Moraes CT, Srivastava S, Kirkinezos I, Oca-Cossio J, van Waveren C, Woischnick M, Diaz F (2002) Mitochondrial DNA structure and function. Int Rev Neurobiol 53:3–23
55. Mott NN, Pak TR (2013) Estrogen signaling and the aging brain: context-dependent considerations for postmenopausal hormone therapy. ISRN Endocrinol 2013:814690
56. Mueck AO, Seeger H (2005) Smoking, estradiol metabolism and hormone replacement therapy. Curr Med Chem Cardiovasc Hematol Agents 3:45–54. doi:10.2174/1568016052773270
57. Murphy DD, Segal M (1997) Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein. Proc Natl Acad Sci USA 94:1482–1487
58. Niizuma K, Endo H, Chan PH (2009) Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. J Neurochem 109(Suppl 1):133–138
59. Nilsson S, Koehler KF, Gustafsson JA (2011) Development of subtype-selective oestrogen receptor-based therapeutics. Nat Rev Drug Discov 10:778–792
60. Noppens RR, Kofler J, Grafe MR, Hurn PD, Traystman RJ (2009) Estradiol after cardiac arrest and cardiopulmonary resuscitation is neuroprotective and mediated through estrogen receptor-beta. J Cereb Blood Flow Metab 29:277–286
61. Panickar KS, Guan G, King MA, Rajakumar G, Simpkins JW (1997) 17beta-estradiol attenuates CREB decline in the rat hippocampus following seizure. J Neurobiol 33:961–967
62. Pelligrino DA, Santizo R, Baughman VL, 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
63. Raval AP, Bhatt A, Saul I (2009) Chronic nicotine exposure inhibits 17beta-estradiol-mediated protection of the hippocampal CA1 region against cerebral ischemia in female rats. Neurosci Lett 458:65–69. doi:10.1016/j.neulet.2009.1004.1021
64. Raval AP, Borges-Garcia R, Diaz F, Sick TJ, Bramlett H (2013) Oral contraceptives and nicotine synergistically exacerbate cerebral ischemic injury in the female brain. Transl Stroke Res 4:402–412
65. Raval AP, Borges-Garcia R, Javier Moreno W, Perez-Pinzon MA, Bramlett H (2013) Periodic 17β-estradiol pretreatment protects rat brain from cerebral ischemic damage via estrogen receptor-β. PLoS One 8:e60716
66. Raval AP, Bramlett H, Perez-Pinzon MA (2006) Estrogen preconditioning protects the hippocampal CA1 against ischemia. Neuroscience 141:1721–1730
67. Raval AP, Dave KR, Saul I, Gonzalez GJ, Diaz F (2012) Synergistic inhibitory effect of nicotine plus oral contraceptive on mitochondrial complex-IV is mediated by estrogen receptor beta in female rats. J Neurochem 121:157–167
68. Raval AP, Hirsch N, Dave KR, Yavagal DR, Bramlett H, Saul I (2011) Nicotine and estrogen synergistically exacerbate cerebral ischemic injury. Neuroscience 181:216–225
69. Raval AP, Saul I, Dave KR, DeFazio RA, Perez-Pinzon MA, Bramlett H (2009) Pretreatment with a single estradiol-17beta bolus activates cyclic-AMP response element binding protein and protects CA1 neurons against global cerebral ischemia. Neuroscience 160:307–318
70. Rissman EF, Heck AL, Leonard JE, Shupnik MA, Gustafsson JA (2002) Disruption of estrogen receptor beta gene impairs spatial learning in female mice. Proc Natl Acad Sci USA 99:3996–4001
71. Ritzel RM, Capozzi LA, McCullough LD (2013) Sex, stroke, and inflammation: the potential for estrogen-mediated immunoprotection in stroke. Horm Behav 63:238–253
72. Roof RL, Hall ED (2000) Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. J Neurotrauma 17:367–388
73. Rusa R, Alkayed NJ, Crain BJ, Traystman RJ, Kimes AS, London ED, Klaus JA, Hurn PD (1999) 17beta-estradiol reduces stroke injury in estrogen-deficient female animals. Stroke 30:1665–1670
74. Ryu H, Lee J, Impey S, Ratan RR, Ferrante RJ (2005) Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons. Proc Natl Acad Sci USA 102:13915–13920
75. Sacco RL, Benjamin EJ, Broderick JP, Dyken M, Easton JD, Feinberg WM, Goldstein LB, Gorelick PB, Howard G, Kittner SJ, Manolio TA, Whisnant JP, Wolf PA (1997) American Heart Association Prevention Conference. IV: prevention and rehabilitation of stroke. Risk factors. Stroke 28:1507–1517
76. Schreihofer DA, Ma Y (2013) Estrogen receptors and ischemic neuroprotection: who, what, where, and when? Brain Res 1514:107–122
77. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J (2003) 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 289:2651–2662
78. Simpkins JW, Dykens JA (2008) Mitochondrial mechanisms of estrogen neuroprotection. Brain Res Rev 57(2):421–430
79. Simpkins JW, Rajakumar G, Zhang YQ, Simpkins CE, Greenwald D, Yu CJ, Bodor N, Day AL (1997) Estrogens may reduce mortality and ischemic damage caused by middle cerebral artery occlusion in the female rat. J Neurosurg 87:724–730
80. Simpkins JW, Singh M, Brock C, Etgen AM (2012) Neuroprotection and estrogen receptors. Neuroendocrinology 96:19–30
81. Soderling TR (1999) The Ca–calmodulin-dependent protein kinase cascade. Trends Biochem Sci 24:232–236
82. Takano T, Oberheim N, Cotrina ML, Nedergaard M (2009) Astrocytes and ischemic injury. Stroke 40:S8–S12
83. Utian WH (2007) NIH and WHI: time for a mea culpa and steps beyond. Menopause 14:1056–1059
84. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI (2001) A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med 345:1243–1249
85. Wade CB, Dorsa DM (2003) Estrogen activation of cyclic adenosine 5′-monophosphate response element-mediated transcription requires the extracellularly regulated kinase/mitogen-activated protein kinase pathway. Endocrinology 144:832–838
86. Walf AA, Ciriza I, Garcia-Segura LM, Frye CA (2008) Antisense oligodeoxynucleotides for estrogen receptor-beta and alpha attenuate estradiol’s modulation of affective and sexual behavior, respectively. Neuropsychopharmacology 33:431–440
87. Walton MR, Dragunow I (2000) Is CREB a key to neuronal survival? Trends Neurosci 23:48–53
88. Wang JM, Hou X, Adeosun S, Hill R, Henry S, Paul I, Irwin RW, Ou XM, Bigler S, Stockmeier C, Brinton RD, Gomez-Sanchez E (2012) A dominant negative ERbeta splice variant determines the effectiveness of early or late estrogen therapy after ovariectomy in rats. PLoS One 7:e33493
89. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, Kotchen T, Curb JD, Black H, Rossouw JE, Aragaki A, Safford M, Stein E, Laowattana S, Mysiw WJ (2003) Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 289:2673–2684
90. Waters EM, Yildirim M, Janssen WG, Lou WY, McEwen BS, Morrison JH, Milner TA (2011) Estrogen and aging affect the synaptic distribution of estrogen receptor beta-immunoreactivity in the CA1 region of female rat hippocampus. Brain Res 1379:86–97
91. Wise PM (2002) Estrogens and neuroprotection. Trends Endocrinol Metab 13:229–230
92. Wise PM, Dubal DB, Wilson ME, Rau SW, Bottner M (2001) Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action. Endocrinology 142:969–973
93. Wu TW, Wang JM, Chen S, Brinton RD (2005) 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 135:59–72
94. Zhang QG, Raz L, Wang R, Han D, De Sevilla L, Yang F, Vadlamudi RK, Brann DW (2009) Estrogen attenuates ischemic oxidative damage via an estrogen receptor alpha-mediated inhibition of NADPH oxidase activation. J Neurosci 29:13823–13836
95. Zhao C, Dahlman-Wright K, Gustafsson JA (2008) Estrogen receptor beta: an overview and update. Nucl Recept Signal 6:e003
96. Zhou Y, Watters JJ, Dorsa DM (1996) Estrogen rapidly induces the phosphorylation of the cAMP response element binding protein in rat brain. Endocrinology 137:2163–2166
97. Zuloaga DG, Zuloaga KL, Hinds LR, Carbone DL, Handa RJ (2014) Estrogen receptor beta expression in the mouse forebrain: age and sex differences. J Comp Neurol 522(2):358–371