THE ESTROGEN-MECHANISM OF NEUROPROTECTION
Abstract
Estrogen is an important steroid hormone signal that regulates multiple tissues and functions in the body.The brain is an important target organ for estrogen. In addition to direct effects, estrogen influences brain function through effects on the vasculature and the immune system. Estrogen influences several neurotransmitter systems, including acetylcholine, serotonin, noradrenalin, and glutamate. There are complex mechanisms that underlie estrogen neuroprotective and neurotrophic actions (genomic, non-genomic kinase signalic pathways and membrane estrogen receptors pathways). Estradiol induces gene transcription and rapid membrane signaling mediated by estrogen receptor alpha (ERα), estrogen receptor-beta (ERβ), and a recently characterized G-protein coupled estrogen receptor, each with distinct distributions and ability to influence estradiol-dependent signaling.Vector-mediated expression of estrogen receptors in the hippocampus provides an innovative research approach and suggests that memory depends on the relative expression of ERα and ERβ interacting with estradiol levels.The potential role of estrogen as a neuroprotective factor and a multicellular mode of estrogen action in the regulation of neuronal survival and neurotrophism is discussed, as are potential future directions for the field.
Key words: estrogen; estrogen receptors; steroid hormone; neuroprotection;
References
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34. Hwang WJ, Lee TY, Kim NS, Kwon JS. The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders. Int J Mol Sci. 2020;22(1):373.
35. Tsialtas I, Georgantopoulos A, Karipidou ME, Kalousi FD, Karra AG, Leonidas DD, Psarra AG. Anti-Apoptotic and Antioxidant Activities of the Mitochondrial Estrogen Receptor Beta in N2A Neuroblastoma Cells. Int J Mol Sci.2021; 22(14):7620.
36. Uddin MS, Rahman MM, Jakaria M, Rahman MS, Hossain MS, Islam A, Ahmed M, Mathew B, Omar UM, Barreto GE, Ashraf GM. Estrogen Signaling in Alzheimer's Disease: Molecular Insights and Therapeutic Targets for Alzheimer's Dementia. Mol Neurobiol.2020; 57(6):2654-2670.
2. Kelly MJ, Qiu J, Ronnekleiv OK. Estrogen signaling in the hypothalamus. Vitam Horm. 2005;71:123–145.
3. Alkayed NJ, Harukuni I, Kimes AS, London ED, Traystman RJ, Hurn PD. Gender-linked brain injury in experimental stroke. Stroke. 1998;29:159–166
4. Darrell W. Brann, Krishnan Dhandapani, Chandramohan Wakade, Virendra B. Mahesh, and Mohammad M. Khan. Neurotrophic and Neuroprotective Actions of Estrogen: Basic Mechanisms and Clinical Implications. Steroids.2007;72(5):381-405.l
5. Park EM, Cho S, Frys KA, Glickstein SB, Zhou P, Anrather J, Ross ME, Iadecola C. Inducible nitric oxide synthase contributes to gender differences in ischemic brain injury. J Cereb Blood Flow Metab. 2006;26:392–401.
6. Miller NR, Jover T, Cohen HW, Zukin RS, Etgen AM. Estrogen can act via estrogen receptor alpha and beta to protect hippocampal neurons against global ischemia-induced cell death. Endocrinology. 2005;146:3070–3079.
7. Plamondon H, Morin A, Charron C. Chronic 17beta-estrogen pretreatment and ischemia-induced hippocampal degeneration and memory impairments: a 6-month survival study. Horm Behav. 2006;50:361–369.
8. McCullough LD, Blizzard K, Simpson ER, Oz OK, Hurn PD. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J Neurosci. 2003;23:8701–8705.
9. Veiga S, Azcoiitia I, Garcia-Segura LM. Extragonadal synthesis of estrogen is protective against kainic acid excitotoxic damage to the hippocampus. Neuroreport. 2005;16:1599–1603
10. Green PS and Simpkins JW: Neuroprotective effects of estrogens: potential mechanisms of action. Int J Dev Neurosci, 2000; 18: 347–358.
11. Honda K, Sawada H, Kihara T, Urushitani M, Nakamizo T, Akaike A, Shimohama S: Phosphatidylinositol 3-kinase mediates neuroprotection by estrogen in cultured cortical neurons. J Neurosci Res 2000; 60: 321–327.
12. Hoffman GE, Merchenthaler I, and Zup SL: Neuroprotection by ovarian hormones in animal models of neurological disease. Endocrine 2006; 29: 217–231
13. Wise PM, Dubal DB, Wilson ME, Rau SW, Bottner M and Rosewell KL: Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies. Brain Res Brain Res Rev 37: 2001; 313–319
14. Shimada K, Kitazato KT, Kinouchi T, Yagi K, Tada Y, Satomi J, Kageji T, Nagahiro S: Activation of estrogen receptor-alpha and of angiotensin-converting enzyme 2 suppresses ischemic brain damage in oophorectomized rats. Hypertension 2011; 57: 1161–1166.
15. Connell B and Saleh TM: Differential Neuroprotection of Selective Estrogen Receptor Agonists against Autonomic Dysfunction and Ischemic Cell Death in Permanent versus Reperfusion Injury. Adv Pharmacol Sci 2011; 976951.
16. Elzer JG, Muhammad S, Wintermantel TM, Regnier-Vigouroux A, Ludwig J, Schütz G, Schwaninger M: Neuronal estrogen receptor-alpha mediates neuroprotection by 17beta-estradiol. J Cereb Blood Flow Metab 2010; 30: 935–942.
17. Farr TD, Carswell HV, Gsell W, Macrae IM: Estrogen receptor beta agonist diarylpropiolnitrile (DPN) does not mediate neuroprotection in a rat model of permanent focal ischemia. Brain Res 2007; 1185: 275–282
18. Miller NR, Jover T, Cohen HW, Zukin RS, Etgen AM: Estrogen can act via estrogen receptor alpha and beta to protect hippocampal neurons against global ischemia-induced cell death. Endocrinology 2005; 146: 3070–3079.
19. Wang L, Kitano H, Hurn PD, Murphy SJ: Estradiol attenuates neuroprotective benefits of isoflurane preconditioning in ischemic mouse brain. J Cereb Blood Flow Metab 2008; 28: 1824–1834.
20. Das A, Smith JA, Gibson C, Varma AK, Ray SK, Banik NL: Estrogen receptor agonists and estrogen attenuate TNF-alpha-induced apoptosis in VSC4.1 motoneurons. J Endocrinol 2011; 208: 171–182.
21. McDowell ML, Das A, Smith JA, Varma AK, Ray SK, Banik NL: Neuroprotective effects of genistein in VSC4.1 motoneurons exposed to activated microglial cytokines. Neurochem Int 2011; 59: 175–84
22. Crawford DK, Mangiardi M, Song B, Patel R, Du S, Sofroniew MV, Voskuhl RR, Tiwari-Woodruff SK:Oestrogen receptor beta ligand: a novel treatment to enhance endogenous functional remyelination. Brain 2010; 133: 2999–3016.
23. Revankar CM CD, Sklar LA, Arterburn JB, Prossnitz ER: A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 2005; 3071625–1
24. Alkayed NJ, Goto S, Sugo N, Joh HD, Klaus J, Crain BJ, Bernard O, Traystman RJ, Hurn PD. Estrogen and Bcl-2: gene induction and effect of transgene in experimental stroke. J Neurosci. 2001;21:7543–7550
25. Wu TW, Wang JM, Chen S, Brinton RD. 17 Beta-estrogen induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expression in rat hippocampal neurons: a potential initiation mechanism for estrogen-induced neuroprotection. Neuroscience . 2005;135:59–72.
26. Choi YC, Lee JH, Hong KW, Lee KS. 17Beta-estrogen prevents focal cerebral ischemic damages via activation of Akt and CREB in association with reduced PTEN phosphorylation in rats. Fundam Clin Pharmacol. 2004;18:547–557.
27. Rau SW, Dubal DB, Bottner M, Gerhold LM, Wise PM. Estrogen attenuates programmed cell death after stroke-like injury. J Neurosci. 2003;23:11420–11426.
28. Fuentes N, Silveyra P. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms.Adv Protein Chem Struct Biol.2019;116: 135-170.
29. He J, Gao Y, Wu G, Lei X, Zhang Y, Pan W, Yu H. Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury.BMC Genet.2018;19(1):46.
30. Engler-Chiurazzi EB, Covey DF, Simpkins JW. A novel mechanism of non-feminizing estrogens in neuroprotection. Exp. Gerontol. 2017;94: 99-102.
31. Yilmaz C, Karali K, Fodelianaki G, Gravanis A, Chavakis T, Charalampopoulos I, Alexaki VI. Neurosteroids as regulators of neuroinflammation.Front Neuroendocrinol. 2019; 55:100788.
32. Wang J, Hou Y, Zhang L, Liu M, Zhao J, Zhang Z, Ma Y, Hou W. Estrogen Attenuates Traumatic Brain Injury by Inhibiting the Activation of Microglia and Astrocyte-Mediated Neuroinflammatory Responses.Mol Neurobiol. 2021;58(3):1052-1061.
33. Kong D, Yan Y, He XY, Yang H, Liang B, Wang J, He Y, Ding Y, Yu H. Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer's Disease.Biomed Res Int. 2019/ 8983752.
34. Hwang WJ, Lee TY, Kim NS, Kwon JS. The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders. Int J Mol Sci. 2020;22(1):373.
35. Tsialtas I, Georgantopoulos A, Karipidou ME, Kalousi FD, Karra AG, Leonidas DD, Psarra AG. Anti-Apoptotic and Antioxidant Activities of the Mitochondrial Estrogen Receptor Beta in N2A Neuroblastoma Cells. Int J Mol Sci.2021; 22(14):7620.
36. Uddin MS, Rahman MM, Jakaria M, Rahman MS, Hossain MS, Islam A, Ahmed M, Mathew B, Omar UM, Barreto GE, Ashraf GM. Estrogen Signaling in Alzheimer's Disease: Molecular Insights and Therapeutic Targets for Alzheimer's Dementia. Mol Neurobiol.2020; 57(6):2654-2670.
Published
2022-12-29
How to Cite
PETROVSKA, Sunchica et al.
THE ESTROGEN-MECHANISM OF NEUROPROTECTION.
Journal of Morphological Sciences, [S.l.], v. 5, n. 3, p. 104-108, dec. 2022.
ISSN 2545-4706.
Available at: <https://jms.mk/jms/article/view/vol5no3-17>. Date accessed: 21 dec. 2024.
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