Benefits of hormone therapy estrogens depend on estrogen type: 17ß-estradiol and conjugated equine estrogens have differential effects on cognitive, anxiety-like, and depressive-like behaviors and increase tryptophan hydroxylase-2 mRNA levels in dorsal raphe nucleus subregions

Frontiers in Neuroscience

Volumn 10, Issue DEC, 2016, Pages

  Hiroi, Ryoko ^a,b   Weyrich, Giulia ^a,b   Koebele, Stephanie V ^a,b   Mennenga, Sarah E ^a,b   Talboom, Joshua S ^a,b   Hewitt, Lauren T ^a,b   Lavery, Courtney N ^a,b   Mendoza, Perla ^a,b   Jordan, Ambra ^a,b   Bimonte Nelson, Heather A ^a,b  

^a ARIZONA STATE UNIVERSITY   (United States)

^b ARIZONA ALZHEIMER S CONSORTIUM   (United States)

Author keywords

Cognition; Estrogen; Learning and memory; Mood; Premarin; Serotonin; Spatial; TpH2

Indexed keywords

CONJUGATED ESTROGEN; ESTRADIOL; MESSENGER RNA; SEROTONIN; TRYPTOPHAN HYDROXYLASE 2;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIDEPRESSANT ACTIVITY; ANXIETY; ARTICLE; BRAIN REGION; COGNITION; CONTROLLED STUDY; CORRELATION ANALYSIS; DELAYED MATCHING TO POSITION TEST; DEPRESSION; DORSAL RAPHE NUCLEUS; ELEVATED PLUS MAZE TEST; FEMALE; FORCED SWIM TEST; GENE EXPRESSION; HORMONAL THERAPY; MAZE TEST; NONHUMAN; OPEN FIELD TEST; OVARIECTOMY; RADIAL ARM MAZE TEST; RAT; SEROTONINERGIC SYSTEM; TASK PERFORMANCE; TISSUE SPECIFICITY; TRANQUILIZING ACTIVITY; UTERUS WEIGHT;

EID: 85009726440     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2016.00517     Document Type: Article

References (133)

1. Acosta, J. I., Hiroi, R., Camp, B. W., Talboom, J. S., and Bimonte-Nelson, H. A. (2013). An update on the cognitive impact of clinically-used hormone therapies in the female rat: models, mazes, and mechanisms. Brain Res. 1514, 18-39. doi: 10.1016/j.brainres.2013.01.016
2. Acosta, J. I., Mayer, L. P., Braden, B. B., Nonnenmacher, S., Mennenga, S. E., and Bimonte-Nelson, H. A. (2010). The cognitive effects of conjugated equine estrogens depend on whether menopause etiology is transitional or surgical. Endocrinology 151, 3795-3804. doi: 10.1210/en.2010-0055
3. Acosta, J. I., Mayer, L., Talboom, J. S., Tsang, C. W., Smith, C. J., Enders, C. K., et al. (2009). Transitional versus surgical menopause in a rodent model: etiology of ovarian hormone loss impacts memory and the acetylcholine system. Endocrinology 150, 4248-4259. doi: 10.1210/en.2008-1802
4. Acosta, M. T., Kardel, P. G., Walsh, K. S., Rosenbaum, K. N., Gioia, G. A., and Packer, R. J. (2011). Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study. Pediatr. Neurol. 45, 241-245. doi: 10.1016/j.pediatrneurol.2011.06.016
5. Alves, S. E., Lopez, V., McEwen, B. S., and Weiland, N. G. (1998). Differential colocalization of estrogen receptor beta (ERbeta) with oxytocin and vasopressin in the paraventricular and supraoptic nuclei of the female rat brain: an immunocytochemical study. Proc. Natl. Acad. Sci. U.S.A. 95, 3281-3286. doi: 10.1073/pnas.95.6.3281
6. Arpels, J. C. (1996). The female brain hypoestrogenic continuum from the premenstrual syndrome to menopause. A hypothesis and review of supporting data. J. Reprod. Med. 41, 633-639.
7. Best, N. R., Rees, M. P., Barlow, D. H., and Cowen, P. J. (1992). Effect of estradiol implant on noradrenergic function and mood in menopausal subjects. Psychoneuroendocrinology 17, 87-93. doi: 10.1016/0306-4530(92)90079-M
8. Bethea, C. L., Mirkes, S. J., Shively, C. A., and Adams, M. R. (2000). Steroid regulation of tryptophan hydroxylase protein in the dorsal raphe of macaques. Biol. Psychiatry 47, 562-576. doi: 10.1016/S0006-3223(99)00156-0
9. Bimonte, H. A., and Denenberg, V. H. (1999). Estradiol facilitates performance as working memory load increases. Psychoneuroendocrinology 24, 161-173. doi: 10.1016/S0306-4530(98)00068-7
10. Bimonte, H. A., Hyde, L. A., Hoplight, B. J., and Denenberg, V. H. (2000). In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze. Physiol. Behav. 70, 311-317. doi: 10.1016/S0031-9384(00)00259-6
11. Bimonte-Nelson, H. A. (2015). The Maze Book: Theories, Practice, and Protocols for Testing Rodent Cognition. New York, NY: Springer; Humana Press.
12. Bimonte-Nelson, H. A., Acosta, J. I., and Talboom, J. S. (2010). Neuroscientists as cartographers: mapping the crossroads of gonadal hormones, memory and age using animal models. Molecules 15, 6050-6105. doi: 10.3390/molecules15096050
13. Bimonte-Nelson, H. A., Francis, K. R., Umphlet, C. D., and Granholm, A. C. (2006). Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats. Eur. J. Neurosci. 24, 229-242. doi: 10.1111/j.1460-9568.2006.04867.x
14. Bimonte-Nelson, H. A., Nelson, M. E., and Granholm, A. C. (2004). Progesterone counteracts estrogen-induced increases in neurotrophins in the aged female rat brain. Neuroreport 15, 2659-2663. doi: 10.1097/00001756-200412030-00021
15. Bimonte-Nelson, H. A., Singleton, R. S., Hunter, C. L., Price, K. L., Moore, A. B., and Granholm, A. C. (2003a). Ovarian hormones and cognition in the aged female rat: I. Long-term, but not short-term, ovariectomy enhances spatial performance. Behav. Neurosci. 117, 1395-1406. doi: 10.1037/0735-7044.117.6.1395
16. Bimonte-Nelson, H. A., Singleton, R. S., Nelson, M. E., Eckman, C. B., Barber, J., Scott, T. Y., et al. (2003b). Testosterone, but not nonaromatizable dihydrotestosterone, improves working memory and alters nerve growth factor levels in aged male rats. Exp. Neurol. 181, 301-312. doi: 10.1016/S0014-4886(03)00061-X
17. Bohacek, J., and Daniel, J. M. (2007). Increased daily handling of ovariectomized rats enhances performance on a radial-maze task and obscures effects of estradiol replacement. Horm. Behav. 52, 237-243. doi: 10.1016/j.yhbeh.2007.04.010
18. Brinton, R. D. (2004). Impact of estrogen therapy on Alzheimer's disease: a fork in the road? CNS Drugs 18, 405-422. doi: 10.2165/00023210-200418070-00001
19. Caldwell, B. M., and Watson, R. I. (1952). An evaluation of psychologic effects of sex hormone administration in aged women. I. Results of therapy after six months. J. Gerontol. 7, 228-244. doi: 10.1093/geronj/7.2.228
20. Campbell, S., and Whitehead, M. (1977). Oestrogen therapy and the menopausal syndrome. Clin. Obstet. Gynaecol. 4, 31-47.
21. Chisholm, N. C., and Juraska, J. M. (2012). Long-term replacement of estrogen in combination with medroxyprogesterone acetate improves acquisition of an alternation task in middle-aged female rats. Behav. Neurosci. 126, 128-136. doi: 10.1037/a0026461
22. Chisholm, N. C., and Juraska, J. M. (2013). Factors influencing the cognitive and neural effects of hormone treatment during aging in a rodent model. Brain Res. 1514, 40-49. doi: 10.1016/j.brainres.2013.02.020
23. Coker, L. H., Hogan, P. E., Bryan, N. R., Kuller, L. H., Margolis, K. L., Bettermann, K., et al. (2009). Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study. Neurology 72, 125-134. doi: 10.1212/01.wnl.0000339036.88842.9e
24. Daniel, J. M., Fader, A. J., Spencer, A. L., and Dohanich, G. P. (1997). Estrogen enhances performance of female rats during acquisition of a radial arm maze. Horm. Behav. 32, 217-225. doi: 10.1006/hbeh.1997.1433
25. Daniel, J. M., Hulst, J. L., and Lee, C. D. (2005). Role of hippocampal M2 muscarinic receptors in the estrogen-induced enhancement of working memory. Neuroscience 132, 57-64. doi: 10.1016/j.neuroscience.2005.01.002
26. Daniel, J. M., Sulzer, J. K., and Hulst, J. L. (2006). Estrogen increases the sensitivity of ovariectomized rats to the disruptive effects produced by antagonism of D2 but not D1 dopamine receptors during performance of a response learning task. Horm. Behav. 49, 38-44. doi: 10.1016/j.yhbeh.2005.05.001
27. Díaz-Véliz, G., Benavides, M. S., Butrón, S., Dussaubat, N., and Mora, S. (1999). Behavioral effects of dopamine agonists and antagonists: influence of estrous cycle, ovariectomy, and estrogen replacement in rats. Pharmacol. Biochem. Behav. 62, 21-29. doi: 10.1016/S0091-3057(98)00097-5
28. Diaz-Veliz, G., Urresta, F., Dussaubat, N., and Mora, S. (1991). Effects of estradiol replacement in ovariectomized rats on conditioned avoidance responses and other behaviors. Physiol. Behav. 50, 61-65. doi: 10.1016/0031-9384(91)90498-D
29. Donner, N., and Handa, R. J. (2009). Estrogen receptor beta regulates the expression of tryptophan-hydroxylase 2 mRNA within serotonergic neurons of the rat dorsal raphe nuclei. Neuroscience 163, 705-718. doi: 10.1016/j.neuroscience.2009.06.046
30. El-Bakri, N. K., Islam, A., Zhu, S., Elhassan, A., Mohammed, A., Winblad, B., et al. (2004). Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: relationship to Morris water maze performance. J. Cell. Mol. Med. 8, 537-544. doi: 10.1111/j.1582-4934.2004.tb00478.x
31. Engler-Chiurazzi, E. B., Talboom, J. S., Braden, B. B., Tsang, C. W., Mennenga, S., Andrews, M., et al. (2012). Continuous estrone treatment impairs spatial memory and does not impact number of basal forebrain cholinergic neurons in the surgically menopausal middle-aged rat. Horm. Behav. 62, 1-9. doi: 10.1016/j.yhbeh.2012.04.004
32. Engler-Chiurazzi, E., Tsang, C., Nonnenmacher, S., Liang, W. S., Corneveaux, J. J., Prokai, L., et al. (2011). Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats. Neurobiol. Aging 32, 680-697. doi: 10.1016/j.neurobiolaging.2009.09.005
33. Estrada-Camarena, E., Fernández-Guasti, A., and López-Rubalcava, C. (2003). Antidepressant-like effect of different estrogenic compounds in the forced swimming test. Neuropsychopharmacology 28, 830-838. doi: 10.1038/sj.npp.1300097
34. Fader, A. J., Johnson, P. E., and Dohanich, G. P. (1999). Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine of a radial-arm maze. Pharmacol. Biochem. Behav. 62, 711-717. doi: 10.1016/S0091-3057(98)00219-6
35. Feng, Z., Cheng, Y., and Zhang, J. T. (2004). Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. J. Pineal Res. 37, 198-206. doi: 10.1111/j.1600-079X.2004.00158.x
36. Files, J. A., Ko, M. G., and Pruthi, S. (2011). Bioidentical hormone therapy. Mayo Clin. Proc. 86, 673-680. doi: 10.4065/mcp.2010.0714
37. Fischer, S., Papageorgiou, A. C., Lloyd, J. A., Oh, S. C., Diller, K., Allegretti, F., et al. (2014). Self-assembly and chemical modifications of bisphenol a on Cu(111): interplay between ordering and thermally activated stepwise deprotonation. ACS Nano 8, 207-215. doi: 10.1021/nn4030493
38. Frick, K. M., Baxter, M. G., Markowska, A. L., Olton, D. S., and Price, D. L. (1995). Age-related spatial reference and working memory deficits assessed in the water maze. Neurobiol. Aging 16, 149-160. doi: 10.1016/0197-4580(94)00155-3
39. Frye, C. A., Walf, A. A., and Paris, J. J. (2010). Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation of 5alpha-reduced progestogens and reduces anxiety-like behavior of middle-aged rats. Behav. Pharmacol. 21, 530-539. doi: 10.1097/FBP.0b013e32833e0a23
40. Garcia-Alloza, M., Gil-Bea, F. J., Diez-Ariza, M., Chen, C. P., Francis, P. T., Lasheras, B., et al. (2005). Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease. Neuropsychologia 43, 442-449. doi: 10.1016/j.neuropsychologia.2004.06.007
41. Gibbs, R. B. (2000). Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol. Aging 21, 107-116. doi: 10.1016/S0197-4580(00)00103-2
42. Gibbs, R. B., and Gabor, R. (2003). Estrogen and cognition: applying preclinical findings to clinical perspectives. J. Neurosci. Res. 74, 637-643. doi: 10.1002/jnr.10811
43. Gleason, C. E., Dowling, N. M., Wharton, W., Manson, J. E., Miller, V. M., Atwood, C. S., et al. (2015). Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled keeps-cognitive and affective study. PLoS Med. 12:e1001833. discussion:e1001833. doi: 10.1371/journal.pmed.1001833
44. Gregoire, A. J., Kumar, R., Everitt, B., Henderson, A. F., and Studd, J. W. (1996). Transdermal oestrogen for treatment of severe postnatal depression. Lancet 347, 930-933. doi: 10.1016/S0140-6736(96)91414-2
45. Gresack, J. E., and Frick, K. M. (2004). Environmental enrichment reduces the mnemonic and neural benefits of estrogen. Neuroscience 128, 459-471. doi: 10.1016/j.neuroscience.2004.06.011
46. Halbreich, U., Rojansky, N., Palter, S., Tworek, H., Hissin, P., and Wang, K. (1995). Estrogen augments serotonergic activity in postmenopausal women. Biol. Psychiatry 37, 434-441. doi: 10.1016/0006-3223(94)00181-2
47. Harburger, L. L., Bennett, J. C., and Frick, K. M. (2007). Effects of estrogen and progesterone on spatial memory consolidation in aged females. Neurobiol. Aging 28, 602-610. doi: 10.1016/j.neurobiolaging.2006.02.019
48. Hersh, A. L., Stefanick, M. L., and Stafford, R. S. (2004). National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA 291, 47-53. doi: 10.1001/jama.291.1.47
49. Hiroi, R., and Neumaier, J. F. (2006). Differential effects of ovarian steroids on anxiety versus fear as measured by open field test and fear-potentiated startle. Behav. Brain Res. 166, 93-100. doi: 10.1016/j.bbr.2005.07.021
50. Hiroi, R., McDevitt, R. A., and Neumaier, J. F. (2006). Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in distinct subregions of rat dorsal raphe nucleus: association between gene expression and anxiety behavior in the open field. Biol. Psychiatry 60, 288-295. doi: 10.1016/j.biopsych.2005.10.019
51. Hiroi, R., McDevitt, R. A., Morcos, P. A., Clark, M. S., and Neumaier, J. F. (2011). Overexpression or knockdown of rat tryptophan hyroxylase-2 has opposing effects on anxiety behavior in an estrogen-dependent manner. Neuroscience 176, 120-131. doi: 10.1016/j.neuroscience.2010.12.019
52. Holmes, M. M., Wide, J. K., and Galea, L. A. (2002). Low levels of estradiol facilitate, whereas high levels of estradiol impair, working memory performance on the radial arm maze. Behav. Neurosci. 116, 928-934. doi: 10.1037/0735-7044.116.5.928
53. Hruska, Z., and Dohanich, G. P. (2007). The effects of chronic estradiol treatment on working memory deficits induced by combined infusion of beta-amyloid (1-42) and ibotenic acid. Horm. Behav. 52, 297-306. doi: 10.1016/j.yhbeh.2007.05.010
54. Hyde, J. F., Morrison, D. G., Drake, K. W., Moore, J. P. Jr., and Maley, B. E. (1996). Vasoactive intestinal polypeptide mRNA and peptide levels are decreased in the anterior pituitary of the human growth hormone-releasing hormone transgenic mouse. J. Neuroendocrinol. 8, 9-15. doi: 10.1111/j.1365-2826.1996.tb00681.x
55. Hyde, L. A., Hoplight, B. J., and Denenberg, V. H. (1998). Water version of the radial-arm maze: learning in three inbred strains of mice. Brain Res. 785, 236-244. doi: 10.1016/S0006-8993(97)01417-0
56. Imai, H., Steindler, D. A., and Kitai, S. T. (1986). The organization of divergent axonal projections from the midbrain raphe nuclei in the rat. J. Comp. Neurol. 243, 363-380. doi: 10.1002/cne.902430307
57. Jarrard, L. E., Okaichi, H., Steward, O., and Goldschmidt, R. B. (1984). On the role of hippocampal connections in the performance of place and cue tasks: comparisons with damage to hippocampus. Behav. Neurosci. 98, 946-954. doi: 10.1037/0735-7044.98.6.946
58. Jones, M. W. (2002). A comparative review of rodent prefrontal cortex and working memory. Curr. Mol. Med. 2, 639-647. doi: 10.2174/1566524023361989
59. Kassis, J. A., and Gorski, J. (1981). Estrogen receptor replenishment. Evidence for receptor recycling. J. Biol. Chem. 256, 7378-7382.
60. Klink, R., Robichaud, M., and Debonnel, G. (2002). Gender and gonadal status modulation of dorsal raphe nucleus serotonergic neurons. Part I: effects of gender and pregnancy. Neuropharmacology 43, 1119-1128. doi: 10.1016/S0028-3908(02)00219-8
61. Koebele, S. V., and Bimonte-Nelson, H. A. (2015). Trajectories and phenotypes with estrogen exposures across the lifespan: what does Goldilocks have to do with it? Horm. Behav. 74, 86-104. doi: 10.1016/j.yhbeh.2015.06.009
62. Kok, H. S., Kuh, D., Cooper, R., Van der Schouw, Y. T., Grobbee, D. E., Wadsworth, M. E., et al. (2006). Cognitive function across the life course and the menopausal transition in a British birth cohort. Menopause 13, 19-27. doi: 10.1097/01.gme.0000196592.36711.a0
63. Korol, D. L., and Kolo, L. L. (2002). Estrogen-induced changes in place and response learning in young adult female rats. Behav. Neurosci. 116, 411-420. doi: 10.1037/0735-7044.116.3.411
64. Kuhl, H. (2005). Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 8(Suppl. 1), 3-63. doi: 10.1080/13697130500148875
65. Lenze, E. J., and Wetherell, J. L. (2011). A lifespan view of anxiety disorders. Dialogues Clin. Neurosci. 13, 381-399.
66. Lindberg, M. K., Movérare, S., Skrtic, S., Gao, H., Dahlman-Wright, K., Gustafsson, J. A., et al. (2003). Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice. Mol. Endocrinol. 17, 203-208. doi: 10.1210/me.2002-0206
67. Liu, M. M., Albanese, C., Anderson, C. M., Hilty, K., Webb, P., Uht, R. M., et al. (2002). Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression. J. Biol. Chem. 277, 24353-24360. doi: 10.1074/jbc.M201829200
68. Lowry, C. A. (2002). Functional subsets of serotonergic neurones: implications for control of the hypothalamic-pituitary-adrenal axis. J. Neuroendocrinol. 14, 911-923. doi: 10.1046/j.1365-2826.2002.00861.x
69. Lowry, N. C., Pardon, L. P., Yates, M. A., and Juraska, J. M. (2010). Effects of long-term treatment with 17 beta-estradiol and medroxyprogesterone acetate on water maze performance in middle aged female rats. Horm. Behav. 58, 200-207. doi: 10.1016/j.yhbeh.2010.03.018
70. Lu, H., Ozawa, H., Nishi, M., Ito, T., and Kawata, M. (2001). Serotonergic neurones in the dorsal raphe nucleus that project into the medial preoptic area contain oestrogen receptor beta. J. Neuroendocrinol. 13, 839-845. doi: 10.1046/j.1365-2826.2001.00695.x
71. Luine, V. N. (2014). Estradiol and cognitive function: past, present and future. Horm. Behav. 66, 602-618. doi: 10.1016/j.yhbeh.2014.08.011
72. Luine, V. N., Richards, S. T., Wu, V. Y., and Beck, K. D. (1998). Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters. Horm. Behav. 34, 149-162. doi: 10.1006/hbeh.1998.1473
73. Luine, V., and Rodriguez, M. (1994). Effects of estradiol on radial arm maze performance of young and aged rats. Behav. Neural Biol. 62, 230-236. doi: 10.1016/S0163-1047(05)80021-4
74. Lund, T. D., Hinds, L. R., and Handa, R. J. (2006). The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus. J. Neurosci. 26, 1448-1456. doi: 10.1523/JNEUROSCI.3777-05.2006
75. Lund, T. D., Rovis, T., Chung, W. C., and Handa, R. J. (2005). Novel actions of estrogen receptor-beta on anxiety-related behaviors. Endocrinology 146, 797-807. doi: 10.1210/en.2004-1158
76. Maki, P. M. (2012). Minireview: effects of different HT formulations on cognition. Endocrinology 153, 3564-3570. doi: 10.1210/en.2012-1175
77. Markham, J. A., and Juraska, J. M. (2002). Aging and sex influence the anatomy of the rat anterior cingulate cortex. Neurobiol. Aging 23, 579-588. doi: 10.1016/S0197-4580(02)00004-0
78. Markham, J. A., Pych, J. C., and Juraska, J. M. (2002). Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the morris water maze. Horm. Behav. 42, 284-293. doi: 10.1006/hbeh.2002.1819
79. Markowska, A. L. (1999). Sex dimorphisms in the rate of age-related decline in spatial memory: relevance to alterations in the estrous cycle. J. Neurosci. 19, 8122-8133.
80. Markowska, A. L., and Savonenko, A. V. (2002). Protective effect of practice on cognition during aging: implications for predictive characteristics of performance and efficacy of practice. Neurobiol. Learn. Mem. 78, 294-320. doi: 10.1006/nlme.2002.4064
81. Matthews, J., and Gustafsson, J. A. (2003). Estrogen signaling: a subtle balance between ER alpha and ER beta. Mol. Interv. 3, 281-292. doi: 10.1124/mi.3.5.281
82. McCarrey, A. C., and Resnick, S. M. (2015). Postmenopausal hormone therapy and cognition. Horm. Behav. 74, 167-172. doi: 10.1016/j.yhbeh.2015.04.018
83. McLaughlin, K. J., Bimonte-Nelson, H., Neisewander, J. L., and Conrad, C. D. (2008). Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: evidence that the duration of hormone deprivation after ovariectomy compromises 17beta-estradiol effectiveness in altering CA1 spines. Horm. Behav. 54, 386-395. doi: 10.1016/j.yhbeh.2008.04.010
84. Mennenga, S. E., Gerson, J. E., Koebele, S. V., Kingston, M. L., Tsang, C. W., Engler-Chiurazzi, E. B., et al. (2015). Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity. Psychoneuroendocrinology 54, 1-13. doi: 10.1016/j.psyneuen.2015.01.002
85. Miotto, E. C., Bullock, P., Polkey, C. E., and Morris, R. G. (1996). Spatial working memory and strategy formation in patients with frontal lobe excisions. Cortex 32, 613-630. doi: 10.1016/S0010-9452(96)80034-7
86. Mørch, L. S., Kjaer, S. K., Keiding, N., Løkkegaard, E., and Lidegaard, Ø. (2016). The influence of hormone therapies on type I and II endometrial cancer: a nationwide cohort study. Int. J. Cancer 138, 1506-1515. doi: 10.1002/ijc.29878
87. Mowla, A., Mosavinasab, M., Haghshenas, H., and Borhani Haghighi, A. (2007). Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer's dementia? A double-blind, placebo-controlled clinical trial. J. Clin. Psychopharmacol. 27, 484-487. doi: 10.1097/jcp.0b013e31814b98c1
88. Nash, M. W., Sugden, K., Huezo-Diaz, P., Williamson, R., Sterne, A., Purcell, S., et al. (2005). Association analysis of monoamine genes with measures of depression and anxiety in a selected community sample of siblings. Am. J. Med. Genet. B Neuropsychiatr. Genet. 135, 33-37. doi: 10.1002/ajmg.b.30063
89. Nomikos, G. G., and Spyraki, C. (1988). Influence of oestrogen on spontaneous and diazepam-induced exploration of rats in an elevated plus maze. Neuropharmacology 27, 691-696. doi: 10.1016/0028-3908(88)90077-9
90. Noristani, H. N., Meadows, R. S., Olabarria, M., Verkhratsky, A., and Rodríguez, J. J. (2011). Increased hippocampal CA1 density of serotonergic terminals in a triple transgenic mouse model of Alzheimer's disease: an ultrastructural study. Cell Death Dis. 2, e210. doi: 10.1038/cddis.2011.79
91. Ohkura, T., Isse, K., Akazawa, K., Hamamoto, M., Yaoi, Y., and Hagino, N. (1995). Long-term estrogen replacement therapy in female patients with dementia of the Alzheimer type: 7 case reports. Dementia 6, 99-107. doi: 10.1159/000106929
92. Okazawa, H., Leyton, M., Benkelfat, C., Mzengeza, S., and Diksic, M. (2000). Statistical mapping analysis of serotonin synthesis images generated in healthy volunteers using positron-emission tomography and alpha-[11C]methyl-L-tryptophan. J. Psychiatry Neurosci. 25, 359-370.
93. Packard, M. G., and Teather, L. A. (1997). Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism. Neurobiol. Learn. Mem. 68, 172-188. doi: 10.1006/nlme.1997.3785
94. Paxinos, G., and Watson, C. (1986). The Rat Brain in Stereotaxic Coordinates, 2nd Edn. San Diego, CA: Academic Press, Inc.
95. Poucet, B. (1990). A further characterization of the spatial problem-solving deficit induced by lesions of the medial frontal cortex in the rat. Behav. Brain Res. 41, 229-237. doi: 10.1016/0166-4328(90)90110-Z
96. Poucet, B., and Herrmann, T. (1990). Septum and medial frontal cortex contribution to spatial problem-solving. Behav. Brain Res. 37, 269-280. doi: 10.1016/0166-4328(90)90139-6
97. Rapp, S. R., Espeland, M. A., Shumaker, S. A., Henderson, V. W., Brunner, R. L., Manson, J. E., et al. (2003). Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 289, 2663-2672. doi: 10.1001/jama.289.20.2663
98. Rissanen, A., Puoliväli, J., van Groen, T., and Riekkinen, P. Jr. (1999). In mice tonic estrogen replacement therapy improves non-spatial and spatial memory in a water maze task. Neuroreport 10, 1369-1372. doi: 10.1097/00001756-199904260-00039
99. Robichaud, M., and Debonnel, G. (2005). Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats. J. Neuroendocrinol. 17, 179-185. doi: 10.1111/j.1365-2826.2005.01292.x
100. Rocca, W. A., Grossardt, B. R., and Shuster, L. T. (2011). Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity. Brain Res. 1379, 188-198. doi: 10.1016/j.brainres.2010.10.031
101. Rodgers, S. P., Bohacek, J., and Daniel, J. M. (2010). Transient estradiol exposure during middle age in ovariectomized rats exerts lasting effects on cognitive function and the hippocampus. Endocrinology 151, 1194-1203. doi: 10.1210/en.2009-1245
102. Rosa-Neto, P., Diksic, M., Okazawa, H., Leyton, M., Ghadirian, N., Mzengeza, S., et al. (2004). Measurement of brain regional alpha-[11C]methyl-L-tryptophan trapping as a measure of serotonin synthesis in medication-free patients with major depression. Arch. Gen. Psychiatry 61, 556-563. doi: 10.1001/archpsyc.61.6.556
103. Rosser, M., Chorich, L., Howard, E., Zamorano, P., and Mahesh, V. B. (1993). Changes in rat uterine estrogen receptor messenger ribonucleic acid levels during estrogen-and progesterone-induced estrogen receptor depletion and subsequent replenishment. Biol. Reprod. 48, 89-98. doi: 10.1095/biolreprod48.1.89
104. Rubinow, D. R., Johnson, S. L., Schmidt, P. J., Girdler, S., and Gaynes, B. (2015). Efficacy of estradiol in perimenopausal depression: so much promise and so few answers. Depress. Anxiety 32, 539-549. doi: 10.1002/da.22391
105. Rubinow, D. R., Schmidt, P. J., and Roca, C. A. (1998). Estrogen-serotonin interactions: implications for affective regulation. Biol. Psychiatry 44, 839-850. doi: 10.1016/S0006-3223(98)00162-0
106. Sandstrom, N. J., and Williams, C. L. (2001). Memory retention is modulated by acute estradiol and progesterone replacement. Behav. Neurosci. 115, 384-393. doi: 10.1037/0735-7044.115.2.384
107. Sandstrom, N. J., and Williams, C. L. (2004). Spatial memory retention is enhanced by acute and continuous estradiol replacement. Horm. Behav. 45, 128-135. doi: 10.1016/j.yhbeh.2003.09.010
108. Sato, B., Nishizawa, Y., Noma, K., Kishimoto, S., and Matsumoto, K. (1983). Chronic estrogen treatment causes an alteration in uterine estrogen receptor dynamics of rats. Biochim. Biophys. Acta 755, 412-419. doi: 10.1016/0304-4165(83)90244-1
109. Sherwin, B. B. (2012). Estrogen and cognitive functioning in women: lessons we have learned. Behav. Neurosci. 126, 123-127. doi: 10.1037/a0025539
110. Shively, C. A., Mirkes, S. J., Lu, N. Z., Henderson, J. A., and Bethea, C. L. (2003). Soy and social stress affect serotonin neurotransmission in primates. Pharmacogenomics J. 3, 114-121. doi: 10.1038/sj.tpj.6500166
111. Shughrue, P. J., Lane, M. V., and Merchenthaler, I. (1997). Comparative distribution of estrogen receptor-alpha and-beta mRNA in the rat central nervous system. J. Comp. Neurol. 388, 507-525. doi: 10.1002/(SICI)1096-9861(19971201)388:4<507::AID-CNE1>3.0.CO;2-6
112. Shumaker, S. A., Legault, C., Kuller, L., Rapp, S. R., Thal, L., Lane, D. S., et al. (2004). Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 291, 2947-2958. doi: 10.1001/jama.291.24.2947
113. Shumaker, S. A., Legault, C., Rapp, S. R., Thal, L., Wallace, R. B., Ockene, J. K., et al. (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. doi: 10.1001/jama.289.20.2651
114. Sichel, D. A., Cohen, L. S., Robertson, L. M., Ruttenberg, A., and Rosenbaum, J. F. (1995). Prophylactic estrogen in recurrent postpartum affective disorder. Biol. Psychiatry 38, 814-818. doi: 10.1016/0006-3223(95)00063-1
115. Sitruk-Ware, R. (2002). Progestogens in hormonal replacement therapy: new molecules, risks, and benefits. Menopause 9, 6-15. doi: 10.1097/00042192-200201000-00003
116. Smith, D. C., Prentice, R., Thompson, D. J., and Herrmann, W. L. (1975). Association of exogenous estrogen and endometrial carcinoma. N. Engl. J. Med. 293, 1164-1167. doi: 10.1056/NEJM197512042932302
117. Sun, H. S., Tsai, H. W., Ko, H. C., Chang, F. M., and Yeh, T. L. (2004). Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women. Genes Brain Behav. 3, 328-336. doi: 10.1111/j.1601-183X.2004.00085.x
118. Swanepoel, A. C., Visagie, A., de Lange, Z., Emmerson, O., Nielsen, V. G., and Pretorius, E. (2016). The clinical relevance of altered fibrinogen packaging in the presence of 17beta-estradiol and progesterone. Thromb. Res. 146, 23-34. doi: 10.1016/j.thromres.2016.08.022
119. Talboom, J. S., West, S. G., Engler-Chiurazzi, E. B., Enders, C. K., Crain, I., and Bimonte-Nelson, H. A. (2014). Learning to remember: cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains. Neurobiol. Aging 35, 2791-2802. doi: 10.1016/j.neurobiolaging.2014.06.008
120. Talboom, J. S., Williams, B. J., Baxley, E. R., West, S. G., and Bimonte-Nelson, H. A. (2008). Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats. Neurobiol. Learn. Mem. 90, 155-163. doi: 10.1016/j.nlm.2008.04.002
121. Tsai, S. A., Stefanick, M. L., and Stafford, R. S. (2011). Trends in menopausal hormone therapy use of US office-based physicians, 2000-2009. Menopause 18, 385-392. doi: 10.1097/gme.0b013e3181f43404
122. Vertes, R. P. (1991). A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat. J. Comp. Neurol. 313, 643-668. doi: 10.1002/cne.903130409
123. Vertes, R. P. (2004). Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51, 32-58. doi: 10.1002/syn.10279
124. Vertes, R. P., Fortin, W. J., and Crane, A. M. (1999). Projections of the median raphe nucleus in the rat. J. Comp. Neurol. 407, 555-582. doi: 10.1002/(SICI)1096-9861(19990517)407:4<555::AID-CNE7>3.0.CO;2-E
125. Waider, J., Araragi, N., Gutknecht, L., and Lesch, K. P. (2011). Tryptophan hydroxylase-2 (TPH2) in disorders of cognitive control and emotion regulation: a perspective. Psychoneuroendocrinology 36, 393-405. doi: 10.1016/j.psyneuen.2010.12.012
126. Walf, A. A., and Frye, C. A. (2008). Conjugated equine estrogen enhances rats' cognitive, anxiety, and social behavior. Neuroreport 19, 789-792. doi: 10.1097/WNR.0b013e3282fe209c
127. Walf, A. A., Rhodes, M. E., and Frye, C. A. (2004). Antidepressant effects of ERbeta-selective estrogen receptor modulators in the forced swim test. Pharmacol. Biochem. Behav. 78, 523-529. doi: 10.1016/j.pbb.2004.03.023
128. Walther, D. J., and Bader, M. (2003). A unique central tryptophan hydroxylase isoform. Biochem. Pharmacol. 66, 1673-1680. doi: 10.1016/S0006-2952(03)00556-2
129. Woolley, C. S., and McEwen, B. S. (1993). Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J. Comp. Neurol. 336, 293-306. doi: 10.1002/cne.903360210
130. You, J. S., Hu, S. Y., Chen, B., and Zhang, H. G. (2005). Serotonin transporter and tryptophan hydroxylase gene polymorphisms in Chinese patients with generalized anxiety disorder. Psychiatr. Genet. 15, 7-11. doi: 10.1097/00041444-200503000-00002
131. Zhang, X., Gainetdinov, R. R., Beaulieu, J. M., Sotnikova, T. D., Burch, L. H., Williams, R. B., et al. (2005). Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 45, 11-16. doi: 10.1016/j.neuron.2004.12.014
132. Ziel, H. K., and Finkle, W. D. (1975). Increased risk of endometrial carcinoma among users of conjugated estrogens. N. Engl. J. Med. 293, 1167-1170. doi: 10.1056/NEJM197512042932303
133. Zweifel, J. E., and O'Brien, W. H. (1997). A meta-analysis of the effect of hormone replacement therapy upon depressed mood. Psychoneuroendocrinology 22, 189-212. doi: 10.1016/S0306-4530(96)00034-0