Bazedoxifene – a promising brain active SERM that crosses the blood brain barrier and enhances spatial memory

Berman, 1997, Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women, Proceedings of the National Academy of Sciences of the United States of America, 94, 8836, 10.1073/pnas.94.16.8836 Boulware, 2013, The memory-enhancing effects of hippocampal estrogen receptor activation involve metabotropic glutamate receptor signaling, The Journal of neuroscience : the official journal of the Society for Neuroscience, 33, 15184, 10.1523/JNEUROSCI.1716-13.2013 Brann, 2007, Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications, Steroids, 72, 381, 10.1016/j.steroids.2007.02.003 Burguete, 2019, The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17beta-oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway, Journal of neuroendocrinology, 31, 10.1111/jne.12751 Cada, 2014, Conjugated estrogens and bazedoxifene, Hosp Pharm, 49, 273, 10.1310/hpj4903-273 Callier, 2000, Stereospecific prevention by 17beta-estradiol of MPTP-induced dopamine depletion in mice, Synapse, 37, 245, 10.1002/1098-2396(20000915)37:4<245::AID-SYN1>3.0.CO;2-5 Chen, 2017, Bazedoxifene and conjugated estrogen combination maintains metabolic homeostasis and benefits liver health, PloS one, 12, 10.1371/journal.pone.0189911 Ciana, 2005, Estrogenic activities in rodent estrogen-free diets, Endocrinology, 146, 5144, 10.1210/en.2005-0660 Ciana, 2001, Engineering of a mouse for the in vivo profiling of estrogen receptor activity, Mol Endocrinol, 15, 1104, 10.1210/mend.15.7.0658 Ciana, 2003, In vivo imaging of transcriptionally active estrogen receptors, Nature medicine, 9, 82, 10.1038/nm809 Colangeli, 2016, Cognitive Reserve in Healthy Aging and Alzheimer’s Disease: A Meta-Analysis of fMRI Studies, American journal of Alzheimer’s disease and other dementias, 31, 443, 10.1177/1533317516653826 de Jong, 2012, Ventral striatal volume is associated with cognitive decline in older people: a population based MR-study, Neurobiology of aging, 33, e421 Du, 2016, The Potential of Gonadal Hormone Signalling Pathways as Therapeutics for Dementia, Journal of molecular neuroscience : MN, 60, 336, 10.1007/s12031-016-0813-9 Duff, 2000, A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy, Hormones and behavior, 38, 262, 10.1006/hbeh.2000.1625 Evans, 2018, Subregional volumes of the hippocampus in relation to cognitive function and risk of dementia, NeuroImage, 178, 129, 10.1016/j.neuroimage.2018.05.041 Fernandez, 2008, Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors, The Journal of neuroscience : the official journal of the Society for Neuroscience, 28, 8660, 10.1523/JNEUROSCI.1968-08.2008 Frick, 2015, Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents, Learn Mem, 22, 472, 10.1101/lm.037267.114 Fuentes, 2019, Estrogen receptor signaling mechanisms, Adv Protein Chem Struct Biol, 116, 135, 10.1016/bs.apcsb.2019.01.001 Gibbs, 2000, Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats, Neurobiology of aging, 21, 107, 10.1016/S0197-4580(00)00103-2 Gonzalez-Burgos, 2012, Selective estrogen receptor modulators regulate dendritic spine plasticity in the hippocampus of male rats, Neural Plast, 2012, 10.1155/2012/309494 Goodall, 2018, Age-associated changes in the blood-brain barrier: comparative studies in human and mouse, Neuropathol Appl Neurobiol, 44, 328, 10.1111/nan.12408 Gruber, 2004, Bazedoxifene (Wyeth), Current opinion in investigational drugs, 5, 1086 Hall, 1999, The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens, Endocrinology, 140, 5566, 10.1210/endo.140.12.7179 Hao, 2007, Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex, Proceedings of the National Academy of Sciences of the United States of America, 104, 11465, 10.1073/pnas.0704757104 Hartley, 2014, Space in the brain: how the hippocampal formation supports spatial cognition, Philos Trans R Soc Lond B Biol Sci, 369, 10.1098/rstb.2012.0510 Heldt, 2007, Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories, Molecular psychiatry, 12, 656, 10.1038/sj.mp.4001957 Hussain, 2016, Modulation of spatial and response strategies by phase of the menstrual cycle in women tested in a virtual navigation task, Psychoneuroendocrinology, 70, 108, 10.1016/j.psyneuen.2016.05.008 Inagaki, 2012, Estrogen-induced memory enhancements are blocked by acute bisphenol A in adult female rats: role of dendritic spines, Endocrinology, 153, 3357, 10.1210/en.2012-1121 Jover-Mengual, 2017, Molecular mechanisms mediating the neuroprotective role of the selective estrogen receptor modulator, bazedoxifene, in acute ischemic stroke: A comparative study with 17beta-estradiol, The Journal of steroid biochemistry and molecular biology, 171, 296, 10.1016/j.jsbmb.2017.05.001 Khorsand, 2018, The Beneficial and Adverse Effects of Raloxifene in Menopausal Women: A Mini Review, J Menopausal Med, 24, 183, 10.6118/jmm.2018.24.3.183 Kim, 2016, 17beta-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms, The Journal of neuroscience : the official journal of the Society for Neuroscience, 36, 3309, 10.1523/JNEUROSCI.0257-15.2016 Komm, 2005, Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity, Endocrinology, 146, 3999, 10.1210/en.2005-0030 Komm, 2014, An overview of current and emerging SERMs, The Journal of steroid biochemistry and molecular biology, 143, 207, 10.1016/j.jsbmb.2014.03.003 Kuroki, 2000, Putative membrane-bound estrogen receptors possibly stimulate mitogen-activated protein kinase in the rat hippocampus, Eur J Pharmacol, 400, 205, 10.1016/S0014-2999(00)00425-8 Lan, 2019, Bazedoxifene protects cerebral autoregulation after traumatic brain injury and attenuates impairments in blood-brain barrier damage: involvement of anti-inflammatory pathways by blocking MAPK signaling, Inflamm Res, 68, 311, 10.1007/s00011-019-01217-z Li, 2004, Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice, Proceedings of the National Academy of Sciences of the United States of America, 101, 2185, 10.1073/pnas.0307313101 Lisman, 2017, Viewpoints: how the hippocampus contributes to memory, navigation and cognition, Nature neuroscience, 20, 1434, 10.1038/nn.4661 Luine, 2014, Estradiol and cognitive function: past, present and future, Hormones and behavior, 66, 602, 10.1016/j.yhbeh.2014.08.011 Luine, 1998, Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters, Hormones and behavior, 34, 149, 10.1006/hbeh.1998.1473 Manson, 2013, Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials, JAMA : the journal of the American Medical Association, 310, 1353, 10.1001/jama.2013.278040 Martinkovich, 2014, Selective estrogen receptor modulators: tissue specificity and clinical utility, Clin Interv Aging, 9, 1437 Maruyama, 2001, Suppression by estrogen receptor beta of AP-1 mediated transactivation through estrogen receptor alpha, The Journal of steroid biochemistry and molecular biology, 78, 177, 10.1016/S0960-0760(01)00083-8 McClure, 2013, 17beta-Estradiol, but not estrone, increases the survival and activation of new neurons in the hippocampus in response to spatial memory in adult female rats, Hormones and behavior, 63, 144, 10.1016/j.yhbeh.2012.09.011 McCutcheon, 2019, Schizophrenia, Dopamine and the Striatum: From Biology to Symptoms, Trends in neurosciences, 42, 205, 10.1016/j.tins.2018.12.004 Milner, 2001, Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites, The Journal of comparative neurology, 429, 355, 10.1002/1096-9861(20010115)429:3<355::AID-CNE1>3.0.CO;2-# Mitra, 2003, Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha, Endocrinology, 144, 2055, 10.1210/en.2002-221069 Mitterling, 2010, Cellular and subcellular localization of estrogen and progestin receptor immunoreactivities in the mouse hippocampus, The Journal of comparative neurology, 518, 2729 Nair, 2016, A simple practice guide for dose conversion between animals and human, J Basic Clin Pharm, 7, 27, 10.4103/0976-0105.177703 O’Brown, 2018, Bridging barriers: a comparative look at the blood-brain barrier across organisms, Genes Dev, 32, 466, 10.1101/gad.309823.117 Ott, 2019, Structural changes in the hippocampus as a biomarker for cognitive improvements in neuropsychiatric disorders: A systematic review, European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 29, 319, 10.1016/j.euroneuro.2019.01.105 Paech, 1997, Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites, Science, 277, 1508, 10.1126/science.277.5331.1508 Penades, 2019, Neuroimaging Studies of Cognitive Function in Schizophrenia, Adv Exp Med Biol, 1118, 117, 10.1007/978-3-030-05542-4_6 Peng, 2017, Efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: A systematic review and meta-analysis, Medicine, 96, e8659, 10.1097/MD.0000000000008659 Phan, 2012, Low doses of 17beta-estradiol rapidly improve learning and increase hippocampal dendritic spines, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 37, 2299, 10.1038/npp.2012.82 Phan, 2011, Rapid effects of estrogen receptor alpha and beta selective agonists on learning and dendritic spines in female mice, Endocrinology, 152, 1492, 10.1210/en.2010-1273 Phan, 2015, Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements, Proceedings of the National Academy of Sciences of the United States of America, 112, 16018, 10.1073/pnas.1522150112 Postma, 1999, Sex differences and menstrual cycle effects in human spatial memory, Psychoneuroendocrinology, 24, 175, 10.1016/S0306-4530(98)00073-0 Quinlan, 2008, Use of cognitive strategies in rats: the role of estradiol and its interaction with dopamine, Hormones and behavior, 53, 185, 10.1016/j.yhbeh.2007.09.015 Reagan-Shaw, 2008, Dose translation from animal to human studies revisited, FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 22, 659, 10.1096/fj.07-9574LSF Rossouw, 2002, Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial, JAMA : the journal of the American Medical Association, 288, 321, 10.1001/jama.288.3.321 Rzemieniec, 2018, Bazedoxifene and raloxifene protect neocortical neurons undergoing hypoxia via targeting ERalpha and PPAR-gamma, Molecular and cellular endocrinology, 461, 64, 10.1016/j.mce.2017.08.014 Sanderson, 2007, Deletion of glutamate receptor-A (GluR-A) AMPA receptor subunits impairs one-trial spatial memory, Behavioral neuroscience, 121, 559, 10.1037/0735-7044.121.3.559 Sandstrom, 2004, Spatial memory retention is enhanced by acute and continuous estradiol replacement, Hormones and behavior, 45, 128, 10.1016/j.yhbeh.2003.09.010 Saville, 2000, Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements, The Journal of biological chemistry, 275, 5379, 10.1074/jbc.275.8.5379 Sbisa, 2017, Spatial working memory in the touchscreen operant platform is disrupted in female rats by ovariectomy but not estrous cycle, Neurobiology of learning and memory, 144, 147, 10.1016/j.nlm.2017.07.010 Schroeder, 2017, Estradiol and raloxifene modulate hippocampal gamma oscillations during a spatial memory task, Psychoneuroendocrinology, 78, 85, 10.1016/j.psyneuen.2017.01.022 Shanmugan, 2014, Estrogen and the prefrontal cortex: towards a new understanding of estrogen’s effects on executive functions in the menopause transition, Human brain mapping, 35, 847, 10.1002/hbm.22218 Sharifi, 2014, Conjugated estrogens combined with bazedoxifene: the first approved tissue selective estrogen complex therapy, Expert review of clinical pharmacology, 7, 281, 10.1586/17512433.2014.893819 Silverman, 2012, Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study, Osteoporos Int, 23, 351, 10.1007/s00198-011-1691-1 Simpson, 2010, A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia, Neuron, 65, 585, 10.1016/j.neuron.2010.02.014 Stell, 2008, Molecular imaging provides novel insights on estrogen receptor activity in mouse brain, Molecular imaging, 7, 283, 10.2310/7290.2008.00027 Summerfield, 2008, Toward an improved prediction of human in vivo brain penetration, Xenobiotica, 38, 1518, 10.1080/00498250802499459 Velazquez-Zamora, 2012, Effects of selective estrogen receptor modulators on allocentric working memory performance and on dendritic spines in medial prefrontal cortex pyramidal neurons of ovariectomized rats, Hormones and behavior, 61, 512, 10.1016/j.yhbeh.2012.01.010 Wang, 2018, Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a meta-analysis of randomized controlled trials, Archives of women’s mental health, 21, 31, 10.1007/s00737-017-0773-2 Wang, 2016, Estrogen’s Effects on Excitatory Synaptic Transmission Entail Integrin and TrkB Transactivation and Depend Upon beta1-integrin function, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 41, 2723, 10.1038/npp.2016.83 Webb, 1995, Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens, Mol Endocrinol, 9, 443 Weickert, 2017, Raloxifene Improves Cognition in Schizophrenia: Spurious Result or Valid Effect?, Frontiers in psychiatry, 8, 202, 10.3389/fpsyt.2017.00202 Weickert, 2015, Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia, Molecular psychiatry, 20, 685, 10.1038/mp.2015.11 Wu, 2014, Sex differences in the adolescent developmental trajectory of parvalbumin interneurons in the hippocampus: a role for estradiol, Psychoneuroendocrinology, 45, 167, 10.1016/j.psyneuen.2014.03.016 Wu, 2015, Analyzing the influence of BDNF heterozygosity on spatial memory response to 17beta-estradiol, Translational psychiatry, 5, e498, 10.1038/tp.2014.143 Yang, 2013, Effects of raloxifene on cognition, mental health, sleep and sexual function in menopausal women: a systematic review of randomized controlled trials, Maturitas, 75, 341, 10.1016/j.maturitas.2013.05.010 Zhang, 2015, Central relaxin-3 receptor (RXFP3) activation reduces elevated, but not basal, anxiety-like behaviour in C57BL/6J mice, Behavioural brain research, 292, 125, 10.1016/j.bbr.2015.06.010 Zhu, 2018