地塞米松（dexamethasone, DEX）是一種人工合成的糖皮質固醇（synthetic glucocorticoids），數十年來被廣泛用作抗發炎藥物 （anti-inflammatory drugs）。同時也用來治療及預防出生體重過低 （extreme low birth weight, ELBW）早產兒的慢性肺部疾病 （chronic respiratory disease）。許多研究指出，新生兒時期的地塞米松治療 （neonatal dexamethasone treatment, NDT）可能對早產兒的情緒 （emotional）和認知 （cognitive）功能產生長期不良的作用。
我們先前的研究指出NDT於雄鼠與雌鼠身上，均會造成長期的不良影響，包含類憂鬱行為（depression-like behavior）的增加，以及雌性大鼠海馬迴 （hippocampus）中α型雌激素受體 （estrogen receptor alpha, ERα）和G蛋白雌激素受體 （G-protein coupled estrogen receptor, GPER so-called GPR30）的表現量下降，且可能為NDT對雌鼠造成長期不良影響的重要原因。我們本研究中驗證是哪一種雌激素受體，為造成NDT青少年雌鼠長期不良反應的主因。
本實驗中使用新生的Wistar大鼠，從出生後第一天到第三天 （postnatal day 1~3, PND 1-3），給予劑量遞減式 （tapering）的DEX皮下注射，自PND 1-3其劑量依序為0.5、0.3和0.1 mg/kg。 於六周齡時，利用開放空間試驗（open field test, OFT）評估NDT大鼠自發性運動功能（spontaneous activity），另外透過強迫游泳試驗 （forced swimming test, FST），評測NDT大鼠的類憂鬱行為。 此外，準備平行組（parallel group）的NDT大鼠，於相同周齡時進行即時聚合酶鏈鎖反應 （real-time polymerase chain reaction, qPCR）評估海馬迴中Erα, Erβ, Gper, Grin1, Grin2a, Grin2b等基因表現。並利用西方墨點法（western blotting）評估mitogen activated protein kinase （MAPK） 的蛋白質表現量及其磷酸化水平（phosphorylation level）。 亦進行了離體胞外電生理記錄 （in vitro extracellular recording），測量海馬迴以高頻刺激誘導的長期增益作用（high frequency stimulation-induced long-term potentiation, HFS-LTP），以評估其海馬迴的神經可塑性（neuroplasticity）。最後利用強迫游泳試驗，以評估投予ERα致效劑（agonist），是否對NDT大鼠具有抗憂鬱（anti-depressant）的功能。
實驗結果顯示，NDT動物青春期前的體重顯著降低，這證明DEX的有效投藥。 OFT的結果顯示NDT動物的自發運動功能未受影響。FST的結果顯示NDT會導致類憂鬱行為的增加。雌性青少年大鼠NDT組的不掙扎的時間（immobility）與對照組相比有顯著增加。而雄性青少年NDT大鼠，則必須先給予高台曝露（platform exposure）之急性壓力處理後，其不掙扎的時間才有顯著增加。qPCR結果顯示，雌性青少年NDT大鼠海馬迴中Erα的表現顯著降低，而Erβ 和 Gper表現量則無明顯差異。NDT雄性青少年大鼠海馬迴中Erα, Erβ 及 Gper的表現量，與控制組間相較，皆無呈現顯著差異。雌性青少年NDT大鼠海馬迴中Grin1, Grin2a 及 Grin2b表現量皆沒有呈現差異。電生理實驗結果顯示NDT母鼠的海馬迴HFS-LTP有顯著下降的現象，而輸入和輸出曲線比值（input/output curve ratio, I/O curve）結果顯示，NDT老鼠與對照組相比有顯著下降的現象。而在配對脈衝促進 (pair-pulse facilitation, PPF) 實驗結果中並無呈現顯著差異。透過表面灌流 (suprafusion) ERα致效劑丙吡唑三醇 （propyl pyrazole triol, PPT）後，NDT雌性大鼠的海馬迴HFS-LTP恢復至正常範圍。而預先投予ERα的拮抗劑methyl-piperidino-pyrazole （MPP），可以阻擋PPT對HFS-LTP的恢復效果；而NDT組經皮下注射PPT後，其不掙扎的時間明顯減少，與對照組相比無顯著差異，顯示其具有降低類憂鬱行為的效果。最後我們利用GPER的致效劑同時為ERα和ERβ的抑制劑氟維司群（fulvestrant）進行驗證，投予fulvestrant無法使NDT雌性大鼠的海馬迴HFS-LTP恢復至正常範圍。 西方墨點法結果顯示，NDT並未影響雌性青少年大鼠海馬迴中MAPK 的蛋白質表現量及磷酸化水平。
綜合上述實驗結果，我們推論NDT青少年雌性大鼠的不良反應，較可能是藉由影響ERα的表現而造成。實驗結果可供後續臨床研究參考，例如投予PPT治療NDT所造成的長期不良反應。

Dexamethasone (DEX) is a synthetic glucocorticoid and frequently used as an anti-inflammation agent for decades. It is also applied neonatally as a therapeutic agent to prevent and cure chronic lung diseases in extremely low birth weight (ELBW) prematurely born infants. However, accumulated results pointed out that neonatal dexamethasone treatment (NDT) may have long-term deleterious effects on emotional and cognitive function.
Our previous results demonstrated that NDT might cause depression-like behavior and alter the hippocampal estrogen receptors (ERs) gene expression, including the alpha type estrogen receptor (ERα) and G-protein coupled estrogen receptor (GPER, so-called GPR30). The change of hippocampal ERs gene expression is responsible for the long-term adverse effect of NDT on female NDT rats. We decided to determine which type of ERs participated in the NDT adverse effects on juvenile female rats.
Briefly, newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3, and 0.1 mg/kg, respectively) from postnatal days one to three (PND 1-3). Animals were then subjected to an open field test (OFT) and forced swimming test (FST) for evaluating spontaneous motor function and depression-like behavior at the age of six weeks old. Additional NDT group animals were prepared and subjected to real-time PCR (qPCR) for evaluating the hippocampal Erα, Erβ, Gper, Grin1, Grin2a, Grin2b gene expression. The western blot was also applied to determine the protein expression and the phosphorylation level of the mitogen-activated protein kinase (MAPK). Furthermore, we used in vitro extracellular recording of the hippocampal high-frequency stimulation-induced long-term potentiation (HFS-LTP) to assess neuroplasticity in the hippocampus. Finally, the NDT animals were administered with ERα agonist then using the forced swimming test to evaluate its anti-depressive function.
Results showed a significant somatic growth impairment of the NDT animals, which proven a successful drug administration. The OFT results showed that NDT did not affect the spontaneous movement of animals. The FST results revealed that the immobility time in the NDT group of juvenile female rats was significantly increased compared with the control group. However, juvenile male rats must be given acute stress (flap-top exposure). The immobility time in the NDT group was significantly increased compared with the control group. Our qPCR results showed that NDT juvenile female rats significantly reduced Erα in the hippocampus. Still, there was no difference between Erβ and Gper. There was no difference in Erα, Erβ and Gper expression in the hippocampus of NDT juvenile male rats. There was no significant difference in the Grin1, Grin2a, and Grin2 expression in the hippocampus of NDT juvenile female rats.
The results of in vitro extracellular recording showed that the hippocampal HFS-LTP of the NDT juvenile female rats had a significant decrease, and the input/output curve ratio (I/O curve) results showed that the NDT rats had a significant decrease compared with the control group. In the pair-pulse facilitation (PPF) experiment, the results showed no significant difference.
Through superfusion (suprafusion) ERα agonist propyl pyrazole triol (PPT), the hippocampal HFS-LTP of NDT juvenile female rats restored to the normal range. Besides, the ERα antagonist methyl-piperidino-pyrazole (MPP) could block the restoration effect of PPT in the hippocampal HFS-LTP. Finally, we used GPER agonist as both ERα and ERβ antagonist fulvestrant, which could not restore the hippocampal HFS-LTP. Western blot results showed no difference in the hippocampal MAPK protein expression and phosphorylation level of NDT female rats. After subcutaneous injection of PPT, the percentage time of immobility of NDT female rats was reduced. There was no difference in the percentage time of immobility between the NDT combined PPT injection group (NDT+PPT) compared with control group animals.
In summary, we conclude that the adverse effect on NDT juvenile female rats could be ascribed to the function of ERα. Our results will be helpful for subsequent clinical administration as a reference, such as the administration of PPT as a pharmacological treatment to reduce adverse reactions caused by NDT.

Reference
Adams, M.M., Fink, S.E., Janssen, W.G., Shah, R.A. & Morrison, J.H. (2004) Estrogen modulates synaptic N-methyl-D-aspartate receptor subunit distribution in the aged hippocampus. J Comp Neurol, 474, 419-426.
Agorastos, A., Pervanidou, P., Chrousos, G.P. & Kolaitis, G. (2018) Early life stress and trauma: developmental neuroendocrine aspects of prolonged stress system dysregulation. Hormones (Athens), 17, 507-520.
Ajj, H., Chesnel, A., Pinel, S., Plenat, F., Flament, S. & Dumond, H. (2013) An alkylphenol mix promotes seminoma derived cell proliferation through an ERalpha36-mediated mechanism. PLoS One, 8, e61758.
Alkalay, A.L., Klein, A.H., Nagel, R.A. & Pomerance, J.J. (1996) Evaluation of hypothalamic-pituitary-adrenal axis in premature infants treated with dexamethasone. Am J Perinatol, 13, 473-477.
Anand, K.S. & Dhikav, V. (2012) Hippocampus in health and disease: An overview. Ann Indian Acad Neurol, 15, 239-246.
Babayan, A.H. & Kramar, E.A. (2013) Rapid effects of oestrogen on synaptic plasticity: interactions with actin and its signalling proteins. J Neuroendocrinol, 25, 1163- 1172.
Baes, C., Martins, C.M., Tofoli, S.M. & Juruena, M.F. (2014) Early Life Stress in Depressive Patients: HPA Axis Response to GR and MR Agonist. Front Psychiatry, 5, 2.
Baez, M.V., Cercato, M.C. & Jerusalinsky, D.A. (2018) NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition. Neural Plast, 2018, 5093048.
Bast, T. (2011) The hippocampal learning-behavior translation and the functional significance of hippocampal dysfunction in schizophrenia. Curr Opin Neurobiol, 21, 492-501.
Bazzari, A.H. & Parri, H.R. (2019) Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: A Steered-Glutamatergic Perspective. Brain Sci, 9.
Belleau, E.L., Treadway, M.T. & Pizzagalli, D.A. (2019) The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology. Biol Psychiatry, 85, 443-453.
Bick, J. & Nelson, C.A. (2016) Early Adverse Experiences and the Developing Brain. Neuropsychopharmacology, 41, 177-196.
Bocchio, M., Nabavi, S. & Capogna, M. (2017) Synaptic Plasticity, Engrams, and Network Oscillations in Amygdala Circuits for Storage and Retrieval of Emotional Memories. Neuron, 94, 731-743.
Borrow, A.P. & Handa, R.J. (2017) Estrogen Receptors Modulation of Anxiety-Like Behavior. Vitam Horm, 103, 27-52.
Boulware, M.I., Heisler, J.D. & Frick, K.M. (2013) The memory-enhancing effects of hippocampal estrogen receptor activation involve metabotropic glutamate receptor signaling. J Neurosci, 33, 15184-15194.
Bowman, R.E., Luine, V., Diaz Weinstein, S., Khandaker, H., DeWolf, S. & Frankfurt, M. (2015) Bisphenol-A exposure during adolescence leads to enduring alterations in cognition and dendritic spine density in adult male and female rats. Horm Behav, 69, 89-97.
Bowman, R.E., Luine, V., Khandaker, H., Villafane, J.J. & Frankfurt, M. (2014) Adolescent bisphenol-A exposure decreases dendritic spine density: role of sex and age. Synapse, 68, 498-507.
Buzsaki, G. (2015) Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning. Hippocampus, 25, 1073-1188.
Chang, K.H., Yeh, C.M., Yeh, C.Y., Huang, C.C. & Hsu, K.S. (2013) Neonatal dexamethasone treatment exacerbates hypoxic-ischemic brain injury. Mol Brain, 6, 18.
Chang, Y.P. (2014) Evidence for adverse effect of perinatal glucocorticoid use on the developing brain. Korean J Pediatr, 57, 101-109.
Chen, C., Gong, X., Yang, X., Shang, X., Du, Q., Liao, Q., Xie, R., Chen, Y. & Xu, J. (2019) The roles of estrogen and estrogen receptors in gastrointestinal disease. Oncol Lett, 18, 5673-5680.
Chen, Y. & Baram, T.Z. (2016) Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks. Neuropsychopharmacology, 41, 197-206.
Chiu, H.F., Chan, M.W.Y., Cheng, C.Y., Chou, J.L., Lin, J.M., Yang, Y.L. & Lu, K.T. (2019) Neonatal Dexamethasone Treatment Suppresses Hippocampal Estrogen Receptor alpha Expression in Adolescent Female Rats. Mol Neurobiol, 56, 2224-2233.
Choi, J.Y., Choi, Y.M., Kim, B., Lee, D.W., Gim, M.S. & Park, S.H. (2015) The effects of childhood abuse on self-reported psychotic symptoms in severe mental illness: Mediating effects of posttraumatic stress symptoms. Psychiatry Res, 229, 389-393.
Christoffel, D.J., Golden, S.A. & Russo, S.J. (2011) Structural and synaptic plasticity in stress-related disorders. Rev Neurosci, 22, 535-549.
Cover, K.K., Maeng, L.Y., Lebron-Milad, K. & Milad, M.R. (2014) Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology. Transl Psychiatry, 4, e422.
Crabtree, G.W. & Gogos, J.A. (2014) Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia. Front Synaptic Neurosci, 6, 28.
Criado-Marrero, M., Gebru, N.T., Gould, L.A., Smith, T.M., Kim, S., Blackburn, R.J., Dickey, C.A. & Blair, L.J. (2019) Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus. Int J Mol Sci, 20.
Cui, J., Shen, Y. & Li, R. (2013) Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends Mol Med, 19, 197-209.
Dahmen, B., Puetz, V.B., Scharke, W., von Polier, G.G., Herpertz-Dahlmann, B. & Konrad, K. (2018) Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions. Dev Neurosci, 40, 13-22.
Dalle, E. & Mabandla, M.V. (2018) Early Life Stress, Depression And Parkinson's Disease: A New Approach. Mol Brain, 11, 18.
Dare, J.B., Arogundade, B., Awoniyi, O.O., Adegoke, A.A. & Adekomi, D.A. (2018) Dexamethasone as endocrine disruptor; type I and type II (anti) oestrogenic actions on the ovary and uterus of adult Wistar rats (Rattus Novergicus). JBRA Assist Reprod, 22, 307-313.
De Vries, W.B., van den Borne, P., Goldschmeding, R., de Weger, R.A., Bal, M.P., van Bel, F. & van Oosterhout, M.F. (2010) Neonatal dexamethasone treatment in the rat leads to kidney damage in adulthood. Pediatr Res, 67, 72-76.
Delpech, J.C., Wei, L., Hao, J., Yu, X., Madore, C., Butovsky, O. & Kaffman, A. (2016) Early life stress perturbs the maturation of microglia in the developing hippocampus. Brain Behav Immun, 57, 79-93.
Derks, N.A., Krugers, H.J., Hoogenraad, C.C., Joels, M. & Sarabdjitsingh, R.A. (2016) Effects of Early Life Stress on Synaptic Plasticity in the Developing Hippocampus of Male and Female Rats. PLoS One, 11, e0164551.
Dhikav, V. & Anand, K. (2011) Potential predictors of hippocampal atrophy in Alzheimer's disease. Drugs Aging, 28, 1-11.
Diering, G.H. & Huganir, R.L. (2018) The AMPA Receptor Code of Synaptic Plasticity. Neuron, 100, 314-329.
Dong, Y., Jiang, A., Yang, H., Chen, H. & Wang, Y. (2014) Phytoestrogen alpha- zearalanol improves memory impairment and hippocampal neurogenesis in ovariectomized mice. ScientificWorldJournal, 2014, 862019.
Drozdowicz, L.B. & Bostwick, J.M. (2014) Psychiatric adverse effects of pediatric corticosteroid use. Mayo Clin Proc, 89, 817-834.
Duarte-Guterman, P., Yagi, S., Chow, C. & Galea, L.A. (2015) Hippocampal learning, memory, and neurogenesis: Effects of sex and estrogens across the lifespan in adults. Horm Behav, 74, 37-52.
Duenas, Z., Caicedo-Mera, J.C. & Torner, L. (2018) Global Effects of Early Life Stress on Neurons and Glial Cells. Curr Pharm Des, 23, 6042-6049.
Elwood, J., Murray, E., Bell, A., Sinclair, M., Kernohan, W.G. & Stockdale, J. (2019) A systematic review investigating if genetic or epigenetic markers are associated with postnatal depression. J Affect Disord, 253, 51-62.
Entringer, S., Buss, C. & Heim, C. (2016) [Early-life stress and vulnerability for disease in later life]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 59, 1255-1261.
Ericson-Neilsen, W. & Kaye, A.D. (2014) Steroids: pharmacology, complications, and practice delivery issues. Ochsner J, 14, 203-207.
Erli, F., Palmos, A.B., Raval, P., Mukherjee, J., Sellers, K.J., Gatford, N.J.F., Moss, S.J., Brandon, N.J., Penzes, P. & Srivastava, D.P. (2020) Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders. Transl Psychiatry, 10, 16.
Ervin, K.S., Lymer, J.M., Matta, R., Clipperton-Allen, A.E., Kavaliers, M. & Choleris, E. (2015a) Estrogen involvement in social behavior in rodents: Rapid and long- term actions. Horm Behav, 74, 53-76.
Ervin, K.S., Mulvale, E., Gallagher, N., Roussel, V. & Choleris, E. (2015b) Activation of the G protein-coupled estrogen receptor, but not estrogen receptor alpha or beta, rapidly enhances social learning. Psychoneuroendocrinology, 58, 51-66.
Eyster, K.M. (2016) The Estrogen Receptors: An Overview from Different Perspectives. Methods Mol Biol, 1366, 1-10.
Fareri, D.S. & Tottenham, N. (2016) Effects of early life stress on amygdala and striatal development. Dev Cogn Neurosci, 19, 233-247.
Feng, Y., Su, M., Si, Y.J., Guo, Q.W., Lin, J., Cao, T., Zhang, X., Fan, M. & Fang, D.Z. (2018) Longitudinal interplays of estrogen receptor alpha gene rs9340799 with social-environmental factors on post-traumatic stress disorder in Chinese Han adolescents after Wenchuan earthquake. Am J Med Genet B Neuropsychiatr Genet, 177, 337-345.
Ford, L.R., Willi, S.M., Hollis, B.W. & Wright, N.M. (1997) Suppression and recovery of the neonatal hypothalamic-pituitary-adrenal axis after prolonged dexamethasone therapy. J Pediatr, 131, 722-726.
Franklin, D.J. & Grossberg, S. (2017) A neural model of normal and abnormal learning and memory consolidation: adaptively timed conditioning, hippocampus, amnesia, neurotrophins, and consciousness. Cogn Affect Behav Neurosci, 17, 24-76.
Fryers, T. & Brugha, T. (2013) Childhood determinants of adult psychiatric disorder. Clin Pract Epidemiol Ment Health, 9, 1-50.
Furuta, M., Numakawa, T., Chiba, S., Ninomiya, M., Kajiyama, Y., Adachi, N., Akema, T. & Kunugi, H. (2013) Estrogen, predominantly via estrogen receptor alpha, attenuates postpartum-induced anxiety- and depression-like behaviors in female rats. Endocrinology, 154, 3807-3816.
Gabor, C., Lymer, J., Phan, A. & Choleris, E. (2015) Rapid effects of the G-protein coupled oestrogen receptor (GPER) on learning and dorsal hippocampus dendritic spines in female mice. Physiol Behav, 149, 53-60.
Goodwill, H.L., Manzano-Nieves, G., Gallo, M., Lee, H.I., Oyerinde, E., Serre, T. & Bath, K.G. (2019) Early life stress leads to sex differences in development of depressive-like outcomes in a mouse model. Neuropsychopharmacology, 44, 711-720.
Gordon, P.V., Young, M.L. & Marshall, D.D. (2001) Focal small bowel perforation: an adverse effect of early postnatal dexamethasone therapy in extremely low birth weight infants. J Perinatol, 21, 156-160.
Grad, I. & Picard, D. (2007) The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol, 275, 2-12.
Hara, Y., Waters, E.M., McEwen, B.S. & Morrison, J.H. (2015) Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse. Physiol Rev, 95, 785-807.
Hardy, R.S., Raza, K. & Cooper, M.S. (2020) Therapeutic glucocorticoids: mechanisms of actions in rheumatic diseases. Nat Rev Rheumatol, 16, 133-144.
Hawley, W.R., Grissom, E.M., Moody, N.M., Dohanich, G.P. & Vasudevan, N. (2014) Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats. Behav Brain Res, 262, 68-73.
Holderbach, R., Clark, K., Moreau, J.L., Bischofberger, J. & Normann, C. (2007) Enhanced long-term synaptic depression in an animal model of depression. Biol Psychiatry, 62, 92-100.
Hong, I., Kim, J., Lee, J., Park, S., Song, B., Kim, J., An, B., Park, K., Lee, H.W., Lee, S., Kim, H., Park, S.H., Eom, K.D., Lee, S. & Choi, S. (2011) Reversible plasticity of fear memory-encoding amygdala synaptic circuits even after fear memory consolidation. PLoS One, 6, e24260.
Hosang, G.M., Fisher, H.L., Hodgson, K., Maughan, B. & Farmer, A.E. (2018) Childhood maltreatment and adult medical morbidity in mood disorders: comparison of unipolar depression with bipolar disorder. Br J Psychiatry, 213, 645-653.
Hu, D., Yu, Z.L., Zhang, Y., Han, Y., Zhang, W., Lu, L. & Shi, J. (2017a) Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress. Sci Rep, 7, 11878.
Hu, Z., Jiang, Y., Huo, X., Yang, Y., Davies, H., Botchway, B.O.A. & Fang, M. (2017b) Prospective Role of MicroRNAs in Depression. Curr Med Chem, 24, 3508- 3521.
Huang, C.C., Lin, H.R., Liang, Y.C. & Hsu, K.S. (2007) Effects of neonatal corticosteroid treatment on hippocampal synaptic function. Pediatr Res, 62, 267-270.
Hwang, W.J., Lee, T.Y., Kim, N.S. & Kwon, J.S. (2020) The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders. Int J Mol Sci, 22.
Ichinohashi, Y., Sato, Y., Saito, A., Ito, M., Watanabe, K., Hayakawa, M., Nakanishi, K., Wakatsuki, A. & Oohira, A. (2013) Dexamethasone administration to the neonatal rat results in neurological dysfunction at the juvenile stage even at low doses. Early Hum Dev, 89, 283-288.
Israel, B.A., Sherman, F.S. & Guthrie, R.D. (1993) Hypertrophic cardiomyopathy associated with dexamethasone therapy for chronic lung disease in preterm infants. Am J Perinatol, 10, 307-310.
Jacome, L.F., Gautreaux, C., Inagaki, T., Mohan, G., Alves, S., Lubbers, L.S. & Luine, V. (2010) Estradiol and ERbeta agonists enhance recognition memory, and DPN, an ERbeta agonist, alters brain monoamines. Neurobiol Learn Mem, 94, 488-498.
Javitt, D.C. (2009) When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. Annu Rev Clin Psychol, 5, 249-275.
Jia, M., Dahlman-Wright, K. & Gustafsson, J.A. (2015) Estrogen receptor alpha and beta in health and disease. Best Pract Res Clin Endocrinol Metab, 29, 557-568.
Joels, M. (2018) Corticosteroids and the brain. J Endocrinol, 238, R121-R130.
Johnson, F.K. & Kaffman, A. (2018) Early life stress perturbs the function of microglia in the developing rodent brain: New insights and future challenges. Brain Behav Immun, 69, 18-27.
Jong, Y.I., Harmon, S.K. & O'Malley, K.L. (2018) Intracellular GPCRs Play Key Roles in Synaptic Plasticity. ACS Chem Neurosci, 9, 2162-2172.
Juruena, M.F. (2014) Early-life stress and HPA axis trigger recurrent adulthood depression. Epilepsy Behav, 38, 148-159.
Juruena, M.F., Eror, F., Cleare, A.J. & Young, A.H. (2020) The Role of Early Life Stress in HPA Axis and Anxiety. Adv Exp Med Biol, 1191, 141-153.
Karemaker, R., Kavelaars, A., ter Wolbeek, M., Tersteeg-Kamperman, M., Baerts, W., Veen, S., Samsom, J.F., Visser, G.H., van Bel, F. & Heijnen, C.J. (2008) Neonatal dexamethasone treatment for chronic lung disease of prematurity alters the hypothalamus-pituitary-adrenal axis and immune system activity at school age. Pediatrics, 121, e870-878.
Kim, J., Schalk, J.C., Koss, W.A., Gremminger, R.L., Taxier, L.R., Gross, K.S. & Frick, K.M. (2019) Dorsal Hippocampal Actin Polymerization Is Necessary for Activation of G-Protein-Coupled Estrogen Receptor (GPER) to Increase CA1 Dendritic Spine Density and Enhance Memory Consolidation. J Neurosci, 39, 9598-9610.
Kim, J., Szinte, J.S., Boulware, M.I. & Frick, K.M. (2016) 17beta-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms. J Neurosci, 36, 3309-3321.
Knierim, J.J. (2015) The hippocampus. Curr Biol, 25, R1116-1121.
Ko, M.C., Hung, Y.H., Ho, P.Y., Yang, Y.L. & Lu, K.T. (2014) Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats. Int J Neuropsychopharmacol, 17, 1995-2004.
Kramar, E.A., Babayan, A.H., Gall, C.M. & Lynch, G. (2013) Estrogen promotes learning-related plasticity by modifying the synaptic cytoskeleton. Neuroscience, 239, 3-16.
Kuo, T., McQueen, A., Chen, T.C. & Wang, J.C. (2015) Regulation of Glucose Homeostasis by Glucocorticoids. Adv Exp Med Biol, 872, 99-126.
Kutschera, J., Tomaselli, J., Maurer, U., Mueller, W. & Urlesberger, B. (2005) Minor neurological dysfunction, cognitive development, and somatic development at the age of 3 to 7 years after dexamethasone treatment in very-low birth-weight infants. Early Hum Dev, 81, 281-287.
Labaka, A., Goni-Balentziaga, O., Lebena, A. & Perez-Tejada, J. (2018) Biological Sex Differences in Depression: A Systematic Review. Biol Res Nurs, 20, 383-392.
Lahdepuro, A., Savolainen, K., Lahti-Pulkkinen, M., Eriksson, J.G., Lahti, J., Tuovinen, S., Kajantie, E., Pesonen, A.K., Heinonen, K. & Raikkonen, K. (2019) The Impact of Early Life Stress on Anxiety Symptoms in Late Adulthood. Sci Rep, 9, 4395.
Li, A., Yau, S.Y., Machado, S., Wang, P., Yuan, T.F. & So, K.F. (2019a) Enhancement of Hippocampal Plasticity by Physical Exercise as a Polypill for Stress and Depression: A Review. CNS Neurol Disord Drug Targets, 18, 294-306.
Li, L., Kang, Y.X., Ji, X.M., Li, Y.K., Li, S.C., Zhang, X.J., Cui, H.X. & Shi, G.M. (2018) Finasteride inhibited brain dopaminergic system and open-field behaviors in adolescent male rats. CNS Neurosci Ther, 24, 115-125.
Li, S.X., Fujita, Y., Zhang, J.C., Ren, Q., Ishima, T., Wu, J. & Hashimoto, K. (2014) Role of the NMDA receptor in cognitive deficits, anxiety and depressive-like behavior in juvenile and adult mice after neonatal dexamethasone exposure. Neurobiol Dis, 62, 124-134.
Li, X.H., Miao, H.H. & Zhuo, M. (2019b) NMDA Receptor Dependent Long-term Potentiation in Chronic Pain. Neurochem Res, 44, 531-538.
Lodish, H., Berk, A., Kaiser, C., Krieger, M., Scott, M. & Bretscher, A. (2008) Molecular cell biology. 6th ed, New York: W.H. Freeman and Company
Lu, Y., Sareddy, G.R., Wang, J., Wang, R., Li, Y., Dong, Y., Zhang, Q., Liu, J., O'Connor, J.C., Xu, J., Vadlamudi, R.K. & Brann, D.W. (2019) Neuron- Derived Estrogen Regulates Synaptic Plasticity and Memory. J Neurosci, 39, 2792-2809.
Luchkina, N.V. & Bolshakov, V.Y. (2019) Mechanisms of fear learning and extinction: synaptic plasticity-fear memory connection. Psychopharmacology (Berl), 236, 163-182.
Luine, V.N. (2014) Estradiol and cognitive function: past, present and future. Horm Behav, 66, 602-618.
Luscher, C. & Malenka, R.C. (2012) NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb Perspect Biol, 4.
Lymer, J., Robinson, A., Winters, B.D. & Choleris, E. (2017) Rapid effects of dorsal hippocampal G-protein coupled estrogen receptor on learning in female mice. Psychoneuroendocrinology, 77, 131-140.
Maeng, L.Y. & Milad, M.R. (2015) Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones. Horm Behav, 76, 106-117.
Magomedova, L. & Cummins, C.L. (2016) Glucocorticoids and Metabolic Control. Handb Exp Pharmacol, 233, 73-93.
Maharjan, S., Serova, L.I. & Sabban, E.L. (2010) Membrane-initiated estradiol signaling increases tyrosine hydroxylase promoter activity with ER alpha in PC12 cells. J Neurochem, 112, 42-55.
Mahmoodzadeh, S. & Dworatzek, E. (2019) The Role of 17beta-Estradiol and Estrogen Receptors in Regulation of Ca(2+) Channels and Mitochondrial Function in Cardiomyocytes. Front Endocrinol (Lausanne), 10, 310.
Maki, P.M. (2013) Critical window hypothesis of hormone therapy and cognition: a scientific update on clinical studies. Menopause, 20, 695-709.
Marques, A.A., Bevilaqua, M.C., da Fonseca, A.M., Nardi, A.E., Thuret, S. & Dias, G.P. (2016) Gender Differences in the Neurobiology of Anxiety: Focus on Adult Hippocampal Neurogenesis. Neural Plast, 2016, 5026713.
Marsden, W.N. (2013) Synaptic plasticity in depression: molecular, cellular and functional correlates. Prog Neuropsychopharmacol Biol Psychiatry, 43, 168- 184.
Matsuda, K.I. (2014) Epigenetic changes in the estrogen receptor alpha gene promoter: implications in sociosexual behaviors. Front Neurosci, 8, 344.
Matsuda, K.I., Mori, H., Nugent, B.M., Pfaff, D.W., McCarthy, M.M. & Kawata, M. (2011) Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior. Endocrinology, 152, 2760-2767.
Meduri, G.U. & Chrousos, G.P. (2020) General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections. Front Endocrinol (Lausanne), 11, 161.
Meijer, O.C., Koorneef, L.L. & Kroon, J. (2018) Glucocorticoid receptor modulators. Ann Endocrinol (Paris), 79, 107-111.
Menard, C., Hodes, G.E. & Russo, S.J. (2016) Pathogenesis of depression: Insights from human and rodent studies. Neuroscience, 321, 138-162.
Menshanov, P.N., Bannova, A.V. & Dygalo, N.N. (2017) Anoxia ameliorates the dexamethasone-induced neurobehavioral alterations in the neonatal male rat pups. Horm Behav, 87, 122-128.
Mieskonen, S., Eronen, M., Malmberg, L.P., Turpeinen, M., Kari, M.A. & Hallman, M. (2003) Controlled trial of dexamethasone in neonatal chronic lung disease: an 8-year follow-up of cardiopulmonary function and growth. Acta Paediatr, 92, 896-904.
Miller, W.L. (2018) The Hypothalamic-Pituitary-Adrenal Axis: A Brief History. Horm Res Paediatr, 89, 212-223.
Murakami, G., Tsurugizawa, T., Hatanaka, Y., Komatsuzaki, Y., Tanabe, N., Mukai, H., Hojo, Y., Kominami, S., Yamazaki, T., Kimoto, T. & Kawato, S. (2006) Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus. Biochem Biophys Res Commun, 351, 553-558.
Nilsson, S. & Gustafsson, J.A. (2011) Estrogen receptors: therapies targeted to receptor subtypes. Clin Pharmacol Ther, 89, 44-55.
Novick, A.M., Levandowski, M.L., Laumann, L.E., Philip, N.S., Price, L.H. & Tyrka, A.R. (2018) The effects of early life stress on reward processing. J Psychiatr Res, 101, 80-103.
Oakley, R.H. & Cidlowski, J.A. (2013) The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol, 132, 1033- 1044.
Onland, W., Cools, F., Kroon, A., Rademaker, K., Merkus, M.P., Dijk, P.H., van Straaten, H.L., Te Pas, A.B., Mohns, T., Bruneel, E., van Heijst, A.F., Kramer, B.W., Debeer, A., Zonnenberg, I., Marechal, Y., Blom, H., Plaskie, K., Offringa, M., van Kaam, A.H. & Group, S.-B.S. (2019) Effect of Hydrocortisone Therapy Initiated 7 to 14 Days After Birth on Mortality or Bronchopulmonary Dysplasia Among Very Preterm Infants Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA, 321, 354-363.
Onland, W., De Jaegere, A.P., Offringa, M. & van Kaam, A.H. (2008) Effects of higher versus lower dexamethasone doses on pulmonary and neurodevelopmental sequelae in preterm infants at risk for chronic lung disease: a meta-analysis. Pediatrics, 122, 92-101.
Ooishi, Y., Mukai, H., Hojo, Y., Murakami, G., Hasegawa, Y., Shindo, T., Morrison, J.H., Kimoto, T. & Kawato, S. (2012) Estradiol rapidly rescues synaptic transmission from corticosterone-induced suppression via synaptic/extranuclear steroid receptors in the hippocampus. Cereb Cortex, 22, 926-936.
Paletta, P., Sheppard, P.A.S., Matta, R., Ervin, K.S.J. & Choleris, E. (2018) Rapid effects of estrogens on short-term memory: Possible mechanisms. Horm Behav, 104, 88-99.
Paterni, I., Granchi, C., Katzenellenbogen, J.A. & Minutolo, F. (2014) Estrogen receptors alpha (ERalpha) and beta (ERbeta): subtype-selective ligands and clinical potential. Steroids, 90, 13-29.
Peng, S.-P. (2014, master dissertation) The Effects of Neonatal Dexamethasone Treatment Hippocampal Glutamatergic Synaptic Transmission in Juvenile Rats.
Pereira, L.M., Bastos, C.P., de Souza, J.M., Ribeiro, F.M. & Pereira, G.S. (2014) Estradiol enhances object recognition memory in Swiss female mice by activating hippocampal estrogen receptor alpha. Neurobiol Learn Mem, 114, 1- 9.
Perri, F., Longo, F., Giuliano, M., Sabbatino, F., Favia, G., Ionna, F., Addeo, R., Della Vittoria Scarpati, G., Di Lorenzo, G. & Pisconti, S. (2017) Epigenetic control of gene expression: Potential implications for cancer treatment. Crit Rev Oncol Hematol, 111, 166-172.
Phuc Le, P., Friedman, J.R., Schug, J., Brestelli, J.E., Parker, J.B., Bochkis, I.M. & Kaestner, K.H. (2005) Glucocorticoid receptor-dependent gene regulatory networks. PLoS Genet, 1, e16.
Pinsonneault, J.K., Sullivan, D., Sadee, W., Soares, C.N., Hampson, E. & Steiner, M. (2013) Association study of the estrogen receptor gene ESR1 with postpartum depression--a pilot study. Arch Womens Ment Health, 16, 499-509.
Pisani, S.L., Neese, S.L., Katzenellenbogen, J.A., Schantz, S.L. & Korol, D.L. (2016) Estrogen Receptor-Selective Agonists Modulate Learning in Female Rats in a Dose- and Task-Specific Manner. Endocrinology, 157, 292-303.
Pooley, J.R., Flynn, B.P., Grontved, L., Baek, S., Guertin, M.J., Kershaw, Y.M., Birnie, M.T., Pellatt, A., Rivers, C.A., Schiltz, R.L., Hager, G.L., Lightman, S.L. & Conway-Campbell, B.L. (2017) Genome-Wide Identification of Basic Helix- Loop-Helix and NF-1 Motifs Underlying GR Binding Sites in Male Rat Hippocampus. Endocrinology, 158, 1486-1501.
Qaheri, S.N., Ali, A.B., Alalwaan, A.A., Ahmed, F.A., Ahmed, M.M. & Kamal, A.H. (2013) Neonatal dexamethasone exposure in rats resulted in hippocampal learning and memory defects with decreased convulsion threshold later in adult life. Neurosciences (Riyadh), 18, 388-390.
Qu, N., Wang, L., Liu, Z.C., Tian, Q. & Zhang, Q. (2013) Oestrogen receptor alpha agonist improved long-term ovariectomy-induced spatial cognition deficit in young rats. Int J Neuropsychopharmacol, 16, 1071-1082.
Raff, H. (2004) Neonatal dexamethasone therapy: short- and long-term consequences. Trends Endocrinol Metab, 15, 351-352.
Ramamoorthy, S. & Cidlowski, J.A. (2016) Corticosteroids: Mechanisms of Action in Health and Disease. Rheum Dis Clin North Am, 42, 15-31, vii.
Reincke, S.A. & Hanganu-Opatz, I.L. (2017) Early-life stress impairs recognition memory and perturbs the functional maturation of prefrontal-hippocampal- perirhinal networks. Sci Rep, 7, 42042.
Reyes-Garcia, S.Z., de Almeida, A.G., Ortiz-Villatoro, N.N., Scorza, F.A., Cavalheiro, E.A. & Scorza, C.A. (2018) Robust Network Inhibition and Decay of Early- Phase LTP in the Hippocampal CA1 Subfield of the Amazon Rodent Proechimys. Front Neural Circuits, 12, 81.
Rivera, H.M., Santollo, J., Nikonova, L.V. & Eckel, L.A. (2012) Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats. Physiol Behav, 105, 188-194.
Roepke, T.A., Ronnekleiv, O.K. & Kelly, M.J. (2011) Physiological consequences of membrane-initiated estrogen signaling in the brain. Front Biosci (Landmark Ed), 16, 1560-1573.
Rozycka, A., Slopien, R., Slopien, A., Dorszewska, J., Seremak-Mrozikiewicz, A., Lianeri, M., Maciukiewicz, M., Warenik-Szymankiewicz, A., Grzelak, T., Kurzawinska, G., Drews, K., Klejewski, A. & Jagodzinski, P.P. (2016) The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. Maturitas, 84, 42-54.
Rubinow, D.R., Johnson, S.L., Schmidt, P.J., Girdler, S. & Gaynes, B. (2015) Efficacy of Estradiol in Perimenopausal Depression: So Much Promise and So Few Answers. Depress Anxiety, 32, 539-549.
Ryan, J., Scali, J., Carriere, I., Peres, K., Rouaud, O., Scarabin, P.Y., Ritchie, K. & Ancelin, M.L. (2011) Oestrogen receptor polymorphisms and late-life depression. Br J Psychiatry, 199, 126-131.
Schiller, C.E., Meltzer-Brody, S. & Rubinow, D.R. (2015) The role of reproductive hormones in postpartum depression. CNS Spectr, 20, 48-59.
Scott, S.M. & Rose, S.R. (2018) Use of Glucocorticoids for the Fetus and Preterm Infant. Clin Perinatol, 45, 93-102.
Sekido, T., Nishio, S.I., Ohkubo, Y., Sekido, K., Kitahara, J., Miyamoto, T. & Komatsu, M. (2019) Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells. In Vitro Cell Dev Biol Anim, 55, 226-236.
Shinsaku, S., Tsutomu, Y. & Kaoru, K. (2005) Effects of 17β-estradiol on chemically induced long-term depression. Neuropharmacology.
Sinauridze, O., Gongadze, N., Kvachadze, I., Tkeshelashvili, B. & Bekaia, G. (2011) [Study of anxiety level and passive avoidance response in rats that in neonatal period undergo the prolonged dexamethasone treatment]. Georgian Med News, 67-70.
Spies, C.M., Strehl, C., van der Goes, M.C., Bijlsma, J.W. & Buttgereit, F. (2011) Glucocorticoids. Best Pract Res Clin Rheumatol, 25, 891-900.
Srivastava, D.P. & Penzes, P. (2011) Rapid estradiol modulation of neuronal connectivity and its implications for disease. Front Endocrinol (Lausanne), 2, 77.
Srivastava, D.P., Woolfrey, K.M. & Penzes, P. (2013) Insights into rapid modulation of neuroplasticity by brain estrogens. Pharmacol Rev, 65, 1318-1350.
Stephens, M.A. & Wand, G. (2012) Stress and the HPA axis: role of glucocorticoids in alcohol dependence. Alcohol Res, 34, 468-483.
Strehl, C., Bijlsma, J.W., de Wit, M., Boers, M., Caeyers, N., Cutolo, M., Dasgupta, B., Dixon, W.G., Geenen, R., Huizinga, T.W., Kent, A., de Thurah, A.L., Listing, J., Mariette, X., Ray, D.W., Scherer, H.U., Seror, R., Spies, C.M., Tarp, S., Wiek, D., Winthrop, K.L. & Buttgereit, F. (2016) Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis, 75, 952-957.
Struber, N., Struber, D. & Roth, G. (2014) Impact of early adversity on glucocorticoid regulation and later mental disorders. Neurosci Biobehav Rev, 38, 17-37.
Sundermann, E.E., Maki, P.M. & Bishop, J.R. (2010) A review of estrogen receptor alpha gene (ESR1) polymorphisms, mood, and cognition. Menopause, 17, 874- 886.
Syed, S.A. & Nemeroff, C.B. (2017) Early Life Stress, Mood, and Anxiety Disorders. Chronic Stress (Thousand Oaks), 1.
Takeuchi, K., Yang, Y., Takayasu, Y., Gertner, M., Hwang, J.Y., Aromolaran, K., Bennett, M.V. & Zukin, R.S. (2015) Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia. Brain Res, 1621, 222-230.
Tan, E.C., Lim, H.W., Chua, T.E., Tan, H.S., Lee, T.M. & Chen, H.Y. (2018) Investigation of variants in estrogen receptor genes and perinatal depression. Neuropsychiatr Dis Treat, 14, 919-925.
Tanaka, M. & Sokabe, M. (2013) Bidirectional modulatory effect of 17beta-estradiol on NMDA receptors via ERalpha and ERbeta in the dentate gyrus of juvenile male rats. Neuropharmacology, 75, 262-273.
Tang, W., Yang, J., Zhao, Z., Lian, Z. & Liang, G. (2017) Intracellular coassembly boosts the anti-inflammation capacity of dexamethasone. Nanoscale, 9, 17717- 17721.
Teissier, A., Le Magueresse, C., Olusakin, J., Andrade da Costa, B.L.S., De Stasi, A.M., Bacci, A., Imamura Kawasawa, Y., Vaidya, V.A. & Gaspar, P. (2019) Early- life stress impairs postnatal oligodendrogenesis and adult emotional behaviour through activity-dependent mechanisms. Mol Psychiatry.
Ter Wolbeek, M., Kavelaars, A., de Vries, W.B., Tersteeg-Kamperman, M., Veen, S., Kornelisse, R.F., van Weissenbruch, M., Baerts, W., Liem, K.D., van Bel, F. & Heijnen, C.J. (2015) Neonatal glucocorticoid treatment: long-term effects on the hypothalamus-pituitary-adrenal axis, immune system, and problem behavior in 14-17 year old adolescents. Brain Behav Immun, 45, 128-138.
Theriault, R.K. & Perreault, M.L. (2019) Hormonal regulation of circuit function: sex, systems and depression. Biol Sex Differ, 10, 12.
Tozzi, A., Durante, V., Manca, P., Di Mauro, M., Blasi, J., Grassi, S., Calabresi, P., Kawato, S. & Pettorossi, V.E. (2019) Bidirectional Synaptic Plasticity Is Driven by Sex Neurosteroids Targeting Estrogen and Androgen Receptors in Hippocampal CA1 Pyramidal Neurons. Front Cell Neurosci, 13, 534.
Van Bodegom, M., Homberg, J.R. & Henckens, M. (2017) Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure. Front Cell Neurosci, 11, 87.
Van der Kooij, M.A., Grosse, J., Zanoletti, O., Papilloud, A. & Sandi, C. (2015) The effects of stress during early postnatal periods on behavior and hippocampal neuroplasticity markers in adult male mice. Neuroscience, 311, 508-518.
Van Weert, L., Buurstede, J.C., Mahfouz, A., Braakhuis, P.S.M., Polman, J.A.E., Sips, H.C.M., Roozendaal, B., Balog, J., de Kloet, E.R., Datson, N.A. & Meijer, O.C. (2017) NeuroD Factors Discriminate Mineralocorticoid From Glucocorticoid Receptor DNA Binding in the Male Rat Brain. Endocrinology, 158, 1511-1522.
Vandewalle, J., Luypaert, A., De Bosscher, K. & Libert, C. (2018) Therapeutic Mechanisms of Glucocorticoids. Trends Endocrinol Metab, 29, 42-54.
Virkud, Y.V., Hornik, C.P., Benjamin, D.K., Laughon, M.M., Clark, R.H., Greenberg, R.G. & Smith, P.B. (2017) Respiratory Support for Very Low Birth Weight Infants Receiving Dexamethasone. J Pediatr, 183, 26-30 e23.
Vrtacnik, P., Ostanek, B., Mencej-Bedrac, S. & Marc, J. (2014) The many faces of estrogen signaling. Biochem Med (Zagreb), 24, 329-342.
Wang, W., Le, A.A., Hou, B., Lauterborn, J.C., Cox, C.D., Levin, E.R., Lynch, G. & Gall, C.M. (2018) Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus. J Neurosci, 38, 7935-7951.
Wang, Y.C., Huang, C.C. & Hsu, K.S. (2010) The role of growth retardation in lasting effects of neonatal dexamethasone treatment on hippocampal synaptic function. PLoS One, 5, e12806.
Waters, E.M., Mitterling, K., Spencer, J.L., Mazid, S., McEwen, B.S. & Milner, T.A. (2009) Estrogen receptor alpha and beta specific agonists regulate expression of synaptic proteins in rat hippocampus. Brain Res, 1290, 1-11.
Watson, C.S., Alyea, R.A., Cunningham, K.A. & Jeng, Y.J. (2010) Estrogens of multiple classes and their role in mental health disease mechanisms. Int J Womens Health, 2, 153-166.
Wei, L., Hao, J., Lacher, R.K., Abbott, T., Chung, L., Colangelo, C.M. & Kaffman, A. (2015) Early-Life Stress Perturbs Key Cellular Programs in the Developing Mouse Hippocampus. Dev Neurosci, 37, 476-488.
Wible, C.G. (2013) Hippocampal physiology, structure and function and the neuroscience of schizophrenia: a unified account of declarative memory deficits, working memory deficits and schizophrenic symptoms. Behav Sci (Basel), 3, 298-315.
Wilson, M.E., Westberry, J.M. & Trout, A.L. (2011) Estrogen receptor-alpha gene expression in the cortex: sex differences during development and in adulthood. Horm Behav, 59, 353-357.
Wingenfeld, K. & Wolf, O.T. (2014) Stress, memory, and the hippocampus. Front Neurol Neurosci, 34, 109-120.
Wu, T.H., Kuo, H.C., Lin, I.C., Chien, S.J., Huang, L.T. & Tain, Y.L. (2014) Melatonin prevents neonatal dexamethasone induced programmed hypertension: histone deacetylase inhibition. J Steroid Biochem Mol Biol, 144 Pt B, 253-259.
Xie, L., Korkmaz, K.S., Braun, K. & Bock, J. (2013) Early life stress-induced histone acetylations correlate with activation of the synaptic plasticity genes Arc and Egr1 in the mouse hippocampus. J Neurochem, 125, 457-464.
Xu, X., Zhou, X., Zhou, X.W., Zhang, Z., Liao, M.J., Gao, Q. & Luo, H.M. (2012) Schizandrin prevents dexamethasone-induced cognitive deficits. Neurosci Bull, 28, 532-540.
Xu, Y., Sheng, H., Tang, Z., Lu, J. & Ni, X. (2015) Inflammation and increased IDO in hippocampus contribute to depression-like behavior induced by estrogen deficiency. Behav Brain Res, 288, 71-78.
Yamada, S. & Kawata, M. (2014) Identification of neural cells activated by mating stimulus in the periaqueductal gray in female rats. Front Neurosci, 8, 421.
Yang, F., Cheung, A., Tao, J., Zhao, N., Wan, W. & Sheng, J. (2019) Physiological dosages of estradiol and diarylpropionitrile decrease depressive behavior and increase tryptophan hydroxylase expression in the dorsal raphe nucleus of rats subjected to the forced swim test. Neuroreport, 30, 66-70.
Yankelevitch-Yahav, R., Franko, M., Huly, A. & Doron, R. (2015) The forced swim test as a model of depressive-like behavior. J Vis Exp.
Yasar, P., Ayaz, G., User, S.D., Gupur, G. & Muyan, M. (2017) Molecular mechanism of estrogen-estrogen receptor signaling. Reprod Med Biol, 16, 4-20.
Yasir, M., Goyal, A., Bansal, P. & Sonthalia, S. (2020) Corticosteroid Adverse Effects, StatPearls.
Yates, N.J., Robertson, D., Rodger, J. & Martin-Iverson, M.T. (2016) Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats. PLoS One, 11, e0167220.
Yen, J.Y., Wang, P.W., Su, C.H., Liu, T.L., Long, C.Y. & Ko, C.H. (2018) Estrogen levels, emotion regulation, and emotional symptoms of women with premenstrual dysphoric disorder: The moderating effect of estrogen receptor 1alpha polymorphism. Prog Neuropsychopharmacol Biol Psychiatry, 82, 216- 223.
Zhang, X.M. & Zhu, J. (2011) Kainic Acid-induced neurotoxicity: targeting glial responses and glia-derived cytokines. Curr Neuropharmacol, 9, 388-398.
Zhang, Z., Hong, J., Zhang, S., Zhang, T., Sha, S., Yang, R., Qian, Y. & Chen, L. (2016) Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice. Psychoneuroendocrinology, 66, 138-149.