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THE ROLE OF NEUROTROPHIC FACTORS OF PLACENTA IN DEVELOPMENT OF THE FETUS BRAIN IN HYPERHOMOCYSTEINEMIA
DOI: https://doi.org/10.29296/24999490-2019-03-01
This review article focuses on modern ideas about the role of neurotrophic factors (BDNF, NGF, NRG1, etc.) in the formation of the placenta and their impact on the development of the fetal nervous system in early ontogenesis. Data on the common effect of neurotrophic factors with vascular endothelial growth factor and metalloproteinases on angiogenesis in the placenta and fetal brain are presented. Issues related to the effect of pro-inflammatory cytokines and oxidative stress on the neurotrophin expression in the placenta, as well as on the fetal brain development are discussed. The pro-apoptotic effect of L-homocysteine on trophoblast cells is associated with oxidative stress, while neurotrophins expressed in the placenta display an anti-apoptotic effect. The oxidative stress is shown to be crucial for long-term impairments in the development of the nervous system and cognitive function in the offspring in hyperhomocysteinemia. This disorder also causes an increase in DYRK1A protein brain level, accompanied by neurodegeneration, the decline in BDNF protein brain level in the mature brain, and impaired brain development in fetuses, leading to cognitive impairment in the offspring. The molecular mechanisms of the effect of prenatal hyperhomocysteinemia on the level of neurotrophins and their precursors in the placenta and fetal brain do not seem completely clear and need further study.
Keywords:
neurotrophins, placenta, fetus, nervous system, prenatal hyperhomocysteinemia, neuroprotection
Список литературы:
- Klein R., Smeyne R.J., Wurst W., Long L.K., Auerbach B.A., Joyner A.L., Barbacid M. Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell. 1993; 75 (1): 113–22. https://doi.org/10.1016/S0092-8674(05)80088-1
- 2. Dhobale M.V., Pisal H.R., Mehendale S.S., Joshi S.R. Differential expression of human placental neurotrophic factors in preterm and term deliveries. Int. J. Dev. Neurosci. 2013; 31 (8): 719–23. https://doi.org/10.1016/j.ijdevneu.2013.09.006
- 3. Garces M.F., Sanchez E., Torres-Sierra A.L., Ruiz-Parra A.I., Angel-Muller E., Alzate J.P., Sanchez A.Y., Gomez M.A., Romero X.C., Castaneda Z.E., Sanchez-Rebordelo E., Dieguez C., Nogueiras R., Caminos J.E. Brain-derived neurotrophic factor is expressed in rat and human placenta and its serum levels are similarly regulated throughout pregnancy in both species. Clin. Endocrinol. (Oxf.). 2014; 81 (1): 141–51. https://doi.org/10.1111/cen.12391
- 4. Tometten M., Blois S., Arck P.C. Nerve growth factor in reproductive biology: link between the immune, endocrine and nervous system? Chem. Immunol. Allergy. 2005; 89: 135–48. https://doi.org/10.1159/000087962
- 5. Mayeur S., Lukaszewski M.A., Breton C., Storme L., Vieau D., Lesage J. Do neurotrophins regulate the feto-placental development? Med. Hypotheses. 2011; 76 (5): 726–8. https://doi.org/10.1016/j.mehy.2011.02.008
- 6. Dhobale M. Neurotrophins: Role in adverse pregnancy outcome. Int. J. Dev. Neurosci. 2014; 37: 8–14. https://doi.org/10.1016/j.ijdevneu.2014.06.005
- 7. Meeker R., Williams K. Dynamic nature of the p75 neurotrophin receptor in response to injury and disease. J. Neuroimmune Pharmacol. 2014; 9 (5): 615–28. https://doi.org/10.1007/s11481-014-9566-9
- 8. Teng K.K., Felice S., Kim T., Hempstead B.L. Understanding proneurotrophin actions: Recent advances and challenges. Dev. Neurobiol. 2010; 70 (5): 350–9. https://doi.org/10.1002/dneu.20768
- 9. Fujita K., Tatsumi K., Kondoh E., Chigusa Y., Mogami H., Fujii T., Yura S., Kakui K., Konishi I. Differential expression and the anti-apoptotic effect of human placental neurotrophins and their receptors. Placenta. 2011; 32 (10): 737–44. https://doi.org/10.1016/j.placenta.2011.07.001
- 10. Kawamura K., Kawamura N., Kumazawa Y., Kumagai J., Fujimoto T., Tanaka T. Brain-derived neurotrophic factor/tyrosine kinase B signaling regulates human trophoblast growth in an in vivo animal model of ectopic pregnancy. Endocrinology. 2011; 152 (3): 1090–100. https://doi.org/10.1210/en.2010-1124
- 11. Kawamura K., Kawamura N., Sato W., Fukuda J., Kumagai J., Tanaka T. Brain-derived neurotrophic factor promotes implantation and subsequent placental development by stimulating trophoblast cell growth and survival. Endocrinology. 2009; 150 (8): 3774–82. https://doi.org/10.1210/en.2009-0213
- 12. Mayeur S., Silhol M., Moitrot E., Barbaux S., Breton C., Gabory A., Vaiman D., Dutriez-Casteloot I., Fajardy I., Vambergue A., Tapia-Arancibia L., Bastide B., Storme L., Junien C., Vieau D., Lesage J. Placental BDNF/TrkB signaling system is modulated by fetal growth disturbances in rat and human. Placenta. 2010; 31 (9): 785–91. https://doi.org/10.1016/j.placenta.2010.06.008
- 13. Sahay A.S., Sundrani D.P., Wagh G.N., Mehendale S.S., Joshi S.R. Neurotrophin levels in different regions of the placenta and their association with birth outcome and blood pressure. Placenta. 2015; 36 (8): 938–43. https://doi.org/10.1016/j.placenta.2015.06.006
- 14. Toti P., Ciarmela P., Florio P., Volpi N., Occhini R., Petraglia F. Human placenta and fetal membranes express nerve growth factor mRNA and protein. J. Endocrinol. Invest. 2006; 29 (4): 337–41. https://doi.org/10.1007/BF03344105
- 15. Sahay A.S., Sundrani D.P., Joshi S.R. Neurotrophins: role in placental growth and development. Vitam. Horm. 2017; 104: 243–61. https://doi.org/10.1016/bs.vh.2016.11.002
- 16. Lazarovici P., Marcinkiewicz C., Lelkes P.I. Cross talk between the cardiovascular and nervous systems: neurotrophic effects of vascular endothelial growth factor (VEGF) and angiogenic effects of nerve growth factor (NGF)-implications in drug development. Curr. Pharm. Des. 2006; 12 (21): 2609–22. https://doi.org/10.2174/138161206777698738
- 17. Oosterbaan A.M., Steegers E.A., Ursem N.T. The effects of homocysteine and folic acid on angiogenesis and VEGF expression during chicken vascular development. Microvasc. Res. 2012; 83 (2): 98–104. https://doi.org/10.1016/j.mvr.2011.11.001
- 18. Xu X., Yang X.Y., He B.W., Yang W.J., Cheng W.W. Placental NRP1 and VEGF expression in pre-eclamptic women and in a homocysteine-treated mouse model of pre-eclampsia. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016; 196: 69–75. https://doi.org/10.1016/j.ejogrb.2015.11.017
- 19. Dammann O., Bueter W., Leviton A., Gressens P., Dammann C.E. Neuregulin-1: a potential endogenous protector in perinatal brain white matter damage. Neonatology. 2008; 93 (3): 182–7. https://doi.org/10.1159/000111119
- 20. Esper R.M., Pankonin M.S., Loeb J.A. Neuregulins: versatile growth and differentiation factors in nervous system development and human disease. Brain Res. Rev. 2006; 51 (2): 161–75. https://doi.org/10.1016/j.brainresrev.2005.11.006
- 21. Hoffmann I., Bueter W., Zscheppang K., Brinkhaus M.J., Liese A., Riemke S., Dork T., Dammann O., Dammann C.E. Neuregulin-1, the fetal endothelium, and brain damage in preterm newborns. Brain Behav. Immun. 2010; 24 (5): 784–91. https://doi.org/10.1016/j.bbi.2009.08.012
- 22. Akbalik M.E., Ketani M.A. Expression of epidermal growth factor receptors and epidermal growth factor, amphiregulin and neuregulin in bovine uteroplacental tissues during gestation. Placenta. 2013; 34 (12): 1232–42. https://doi.org/10.1016/j.placenta.2013.09.019
- 23. Fock V., Plessl K., Draxler P., Otti G.R., Fiala C., Knofler M., Pollheimer J. Neuregulin-1-mediated ErbB2-ErbB3 signalling protects human trophoblasts against apoptosis to preserve differentiation. J. Cell Sci. 2015; 128 (23): 4306–16. https://doi.org/10.1242/jcs.176933
- 24. Bilbo S.D., Schwarz J.M. Early-life programming of later-life brain and behavior: a critical role for the immune system. Front. Behav. Neurosci. 2009; 3: 14. https://doi.org/10.3389/neuro.08.014.2009
- 25. Hsiao E.Y., Patterson P.H. Placental regulation of maternal-fetal interactions and brain development. Dev. Neurobiol. 2012; 72 (10): 1317–26. https://doi.org/10.1002/dneu.22045
- 26. Smith S.E., Li J., Garbett K., Mirnics K., Patterson P.H. Maternal immune activation alters fetal brain development through interleukin-6. J. Neurosci. 2007; 27 (40): 10695–702. https://doi.org/10.1523/JNEUROSCI.2178-07.2007
- 27. Gilmore J.H., Jarskog L.F., Vadlamudi S. Maternal infection regulates BDNF and NGF expression in fetal and neonatal brain and maternal-fetal unit of the rat. J. Neuroimmunol. 2003; 138 (1-2): 49–55. https://doi.org/10.1016/S0165-5728(03)00095-X
- 28. Gilmore J.H., Jarskog L.F., Vadlamudi S. Maternal poly I:C exposure during pregnancy regulates TNF alpha, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat. J. Neuroimmunol. 2005; 159 (1–2): 106–12. https://doi.org/10.1016/j.jneuroim.2004.10.008
- 29. Barrientos R.M., Sprunger D.B., Campeau S., Watkins L.R., Rudy J.W., Maier S.F. BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1beta administration. J. Neuroimmunol. 2004; 155 (1–2): 119–26. https://doi.org/10.1016/j.jneuroim.2004.06.009
- 30. Tong L., Balazs R., Soiampornkul R., Thangnipon W., Cotman C.W. Interleukin-1 beta impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol. Aging. 2008; 29 (9): 1380–93. https://doi.org/10.1016/j.neurobiolaging.2007.02.027
- 31. Dhobale M., Mehendale S., Pisal H., Nimbargi V., Joshi S. Reduced maternal and cord nerve growth factor levels in preterm deliveries. Int. J. Dev. Neurosci. 2012; 30 (2): 99–103. https://doi.org/10.1016/j.ijdevneu.2011.12.007
- 32. Arutjunyan A., Kozina L., Stvolinskiy S., Bulygina Y., Mashkina A., Khavinson V. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia. Int. J. Clin. Exp. Med. 2012; 5 (2): 179–85. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342713/
- 33. Baydas G., Koz S.T., Tuzcu M., Nedzvetsky V.S. Melatonin prevents gestational hyperhomocysteinemia-associated alterations in neurobehavioral developments in rats. J. Pineal Res. 2008; 44 (2): 181–8. https://doi.org/10.1111/j.1600-079X.2007.00506.x
- 34. Baydas G., Koz S.T., Tuzcu M., Nedzvetsky V.S., Etem E. Effects of maternal hyperhomocysteinemia induced by high methionine diet on the learning and memory performance in offspring. Int. J. Dev. Neurosci. 2007; 25 (3): 133–9. https://doi.org/10.1016/j.ijdevneu.2007.03.001
- 35. Gerasimova E., Yakovleva O., Burkhanova G., Khaertdinov N., Sitdikova G., Ziyatdinova G. Effects of maternal hyperhomocysteinemia on the early physical development and neurobehavioral maturation of rat offspring. BioNanoScience. 2017; 7 (1): 155–8. https://doi.org/10.1007/s12668-016-0326-6
- 36. Makhro A.V., Mashkina A.P., Solenaya O.A., Trunova O.A., Kozina L.S., Arutyunian A.V., Bulygina E.R. Prenatal hyperhomocysteinemia as a model of oxidative stress of the brain. Bull. Exp. Biol. Med. 2008; 146 (1): 33–5. https://doi.org/10.1007/s10517-008-0233-0
- 37. Махро А.В., Машкина А.П., Соленая О.А., Трунова О.А., Тюлина О.В., Булыгина Е.Р., Болдырев А.А. Карнозин защищает от окислительного стресса, вызванного гипергомоцистеинемией. Нейрохимия. 2008; 2 (3): 202–8. [Makhro A.V., Mashkina A.P., Solenaya O.A., Trunova O. A., Tyulina O.V., Bulygina E.R., Boldyrev A.A. Carnosine protects cells from oxidative stress induced by hyperhomocysteinemia. Nejrohimiya. 2008; 2 (3): 202–8 (in Russian)]
- 38. Griffiths R., Grieve A., Allen S., Olverman H.J. Neuronal and glial plasma membrane carrier-mediated uptake of L-homocysteate is not selectively blocked by beta-p-chlorophenylglutamate. Neurosci. Lett. 1992; 147 (2): 175–8. https://doi.org/10.1016/0304-3940(92)90588-X
- 39. Арутюнян А.В., Козина Л.С., Арутюнов В.А. Токсическое влияние пренатальной гипергомоцистеинемии на потомство (экспериментальное исследование). Журнал акушерства и женских болезней. 2010; 59 (4): 16–23. [Arutjunyan A.V., Kozina L.S., Arutyonov V.A. Toxic effect of prenatal hyperhomocysteinemia on offspring (experimental study). Z. Akus. Zen. Bolezn. 2010; 59 (4): 16–23 (in Russian)]
- 40. Арутюнян А.В., Пустыгина А.В., Милютина Ю.П., Залозняя И.В., Козина Л.С. Молекулярные маркеры окислительного стресса у потомства при экспериментальной гипергомоцистеинемии. Молекулярная медицина. 2015; 5: 41–6. [Arutjunyan A.V., Pustygina A.V., Milyutina Yu.P., Zaloznyaya I.V., Kozina L.S. Prenatal hyperhomocysteinemia and oxidative stress profile in the rat offspring. Molekulyarnaya meditsina. 2015; 5: 41–6 (in Russian)]
- 41. Пустыгина А.В., Милютина Ю.П., Залозняя И.В., Арутюнян А.В. Показатели окислительного стресса в мозге новорожденных крысят, перенесших пренатальную гипергомоцистеинемию. Нейрохимия. 2015; 32 (1): 71–7. [Pustygina A.V., Milyutina Yu.P., Zaloznyaya I.V., Arutyunyan A.V. Indices of oxidative stress in the brain of newborn rats subjected to prenatal hyperhomocystinemia. Nejrohimiya. 2015; 32(1): 71–7. https://doi.org/10.7868/S1027813315010070 (in Russian)]
- 42. Khavinson V., Ribakova Y., Kulebiakin K., Vladychenskaya E., Kozina L., Arutjunyan A., Boldyrev A. Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes. Rejuvenation Res. 2011; 14 (5): 535–41. https://doi.org/10.1089/rej.2011.1172
- 43. Sable P., Kale A., Joshi A., Joshi S. Maternal micronutrient imbalance alters gene expression of BDNF, NGF, TrkB and CREB in the offspring brain at an adult age. Int. J. Dev. Neurosci. 2014; 34: 24–32. https://doi.org/10.1016/j.ijdevneu.2014.01.003
- 44. Di Simone N., Maggiano N., Caliandro D., Riccardi P., Evangelista A., Carducci B., Caruso A. Homocysteine induces trophoblast cell death with apoptotic features. Biol. Reprod. 2003; 69 (4): 1129–34. https://doi.org/10.1095/biolreprod.103.015800
- 45. Kamudhamas A., Pang L., Smith S.D., Sadovsky Y., Nelson D.M. Homocysteine thiolactone induces apoptosis in cultured human trophoblasts: a mechanism for homocysteine-mediated placental dysfunction? Am. J. Obstet. Gynecol. 2004; 191 (2): 563–71. https://doi.org/10.1016/j.ajog.2004.01.037
- 46. Koz S.T., Gouwy N.T., Demir N., Nedzvetsky V.S., Etem E., Baydas G. Effects of maternal hyperhomocysteinemia induced by methionine intake on oxidative stress and apoptosis in pup rat brain. Int. J. Dev. Neurosci. 2010; 28 (4): 325–9. https://doi.org/10.1016/j.ijdevneu.2010.02.006
- 47. Di Simone N., Riccardi P., Maggiano N., Piacentani A., D’Asta M., Capelli A., Caruso A. Effect of folic acid on homocysteine-induced trophoblast apoptosis. Mol. Hum. Reprod. 2004; 10 (9): 665–9. https://doi.org/10.1093/molehr/gah091
- 48. Suhara T., Fukuo K., Yasuda O., Tsubakimoto M., Takemura Y., Kawamoto H., Yokoi T., Mogi M., Kaimoto T., Ogihara T. Homocysteine enhances endothelial apoptosis via upregulation of Fas-mediated pathways. Hypertension. 2004; 43 (6): 1208–13. https://doi.org/10.1161/01.HYP.0000127914.94292.76
- 49. Cai B., Li X., Wang Y., Liu Y., Yang F., Chen H., Yin K., Tan X., Zhu J., Pan Z., Wang B., Lu Y. Apoptosis of bone marrow mesenchymal stem cells caused by homocysteine via activating JNK signal. PLoS One. 2013; 8 (5): e63561. https://doi.org/10.1371/journal.pone.0063561
- 50. Lanoix D., Lacasse A.A., Reiter R.J., Vaillancourt C. Melatonin: the smart killer: the human trophoblast as a model. Mol. Cell. Endocrinol. 2012; 348 (1): 1–11. https://doi.org/10.1016/j.mce.2011.08.025
- 51. Stagni F., Giacomini A., Emili M., Guidi S., Bartesaghi R. Neurogenesis impairment: An early developmental defect in Down syndrome. Free Radic. Biol. Med 2018; 114: 15–32. https://doi.org/10.1016/j.freeradbiomed.2017.07.026
- 52. Nakano-Kobayashi A., Awaya T., Kii I., Sumida Y., Okuno Y., Yoshida S., Sumida T., Inoue H., Hosoya T., Hagiwara M. Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice. Proc. Natl. Acad. Sci. U.S.A. 2017; 114 (38): 10268–73. https://doi.org/10.1073/pnas.1704143114
- 53. Baloula V., Fructuoso M., Kassis N., Gueddouri D., Paul J.L., Janel N. Homocysteine-lowering gene therapy rescues signaling pathways in brain of mice with intermediate hyperhomocysteinemia. Redox Biol. 2018; 19: 200–9. https://doi.org/10.1016/j.redox.2018.08.015
- 54. Janel N., Alexopoulos P., Badel A., Lamari F., Camproux A.C., Lagarde J., Simon S., Feraudet-Tarisse C., Lamourette P., Arbones M., Paul J.L., Dubois B., Potier M.C., Sarazin M., Delabar J.M. Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer’s disease. Transl. Psychiatry. 2017; 7 (6): e1154. https://doi.org/10.1038/tp.2017.123
- 55. Souchet B., Latour A., Gu Y., Daubigney F., Paul J.L., Delabar J.M., Janel N. Molecular rescue of DYRK1A overexpression in cystathionine beta synthase-deficient mouse brain by enriched environment combined with voluntary exercise. J. Mol. Neurosci. 2015; 55 (2): 318–23. https://doi.org/10.1007/s12031-014-0324-5
- 56. Deinhardt K., Chao M.V. Shaping neurons: Long and short range effects of mature and proBDNF signalling upon neuronal structure. Neuropharmacology. 2014; 76: 603–9. https://doi.org/10.1016/j.neuropharm.2013.04.054
- 57. Woo N.H., Teng H.K., Siao C.J., Chiaruttini C., Pang P.T., Milner T.A., Hempstead B.L., Lu B. Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat. Neurosci. 2005; 8 (8): 1069–77. https://doi.org/10.1038/nn1510
- 58. Yang J., Harte-Hargrove L.C., Siao C.J., Marinic T., Clarke R., Ma Q., Jing D., Lafrancois J.J., Bath K.G., Mark W., Ballon D., Lee F.S., Scharfman H.E., Hempstead B.L. ProBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Cell Rep. 2014; 7 (3): 796–806. https://doi.org/10.1016/j.celrep.2014.03.040
- 59. Peng S., Wuu J., Mufson E.J., Fahnestock M. Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J. Neuropathol. Exp. Neurol. 2004; 63 (6): 641–9. https://doi.org/10.1093/jnen/63.6.641
- 60. Tiveron C., Fasulo L., Capsoni S., Malerba F., Marinelli S., Paoletti F., Piccinin S., Scardigli R., Amato G., Brandi R., Capelli P., D’Aguanno S., Florenzano F., La Regina F., Lecci A., Manca A., Meli G., Pistillo L., Berretta N., Nistico R., Pavone F., Cattaneo A. ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice. Cell Death Differ. 2013; 20 (8): 1017–30. https://doi.org/10.1038/cdd.2013.22