Abstract
Spinal motor neurons have the longest axons that innervate the skeletal muscles of the central nervous system. Motor neuron diseases caused by spinal motor neuron cell death are incurable due to the unique and irreplaceable nature of their neural circuits. Understanding the mechanisms of neurogenesis, neuritogenesis, and synaptogenesis in motor neurons will allow investigators to develop new in vitro models and regenerative therapies for motor neuron diseases. In particular, small molecules can directly reprogram and convert into neural stem cells and neurons, and promote neuron-like cell differentiation. Prostaglandins are known to have a role in the differentiation and tissue regeneration of several cell types and organs. However, the involvement of prostaglandins in the differentiation of motor neurons from neural stem cells is poorly understood. The general cell line used in research on motor neuron diseases is the mouse neuroblastoma and spinal motor neuron fusion cell line NSC-34. Recently, our laboratory reported that prostaglandin E2 and prostaglandin D2 enhanced the conversion of NSC-34 cells into motor neuron-like cells with neurite outgrowth. Moreover, we found that prostaglandin E2-differentiated NSC-34 cells had physiological and electrophysiological properties of mature motor neurons. In this review article, we provide contemporary evidence on the effects of prostaglandins, particularly prostaglandin E2 and prostaglandin D2, on differentiation and neural conversion. We also discuss the potential of prostaglandins as candidates for the development of new therapeutic drugs for motor neuron diseases.
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References
Aglah C, Gordon T, Posse de Chaves EI (2008) cAMP promotes neurite outgrowth and extension through protein kinase A but independently of Erk activation in cultured rat motoneurons. Neuropharmacology 55:8–17. https://doi.org/10.1016/j.neuropharm.2008.04.005
Amaya F, Samad TA, Barrett L, Broom DC, Woolf CJ (2009) Periganglionic inflammation elicits a distally radiating pain hypersensitivity by promoting COX-2 induction in the dorsal root ganglion. Pain 142:59–67. https://doi.org/10.1016/j.pain.2008.11.013
Arber S, Han B, Mendelsohn M, Smith M, Jessell TM, Sockanathan S (1999) Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 23:659–674. https://doi.org/10.1016/S0896-6273(01)80026-X
Bento-Abreu A, Tabernero A, Medina JM (2007) Peroxisome proliferator-activated receptor-alpha is required for the neurotrophic effect of oleic acid in neurons. J Neurochem 103:871–881. https://doi.org/10.1111/j.1471-4159.2007.04807.x
Boulting GL, Kiskinis E, Croft GF, Amoroso MW, Oakley DH, Wainger BJ, Williams DJ, Kahler DJ, Yamaki M, Davidow L, Rodolfa CT, Dimos JT, Mikkilineni S, MacDermott AB, Woolf CJ, Henderson CE, Wichterle H, Eggan K (2011) A functionally characterized test set of human induced pluripotent stem cells. Nat Biotechnol 29:279–287. https://doi.org/10.1038/nbt.1783
Chi L, Ke Y, Luo C, Li B, Gozal D, Kalyanaraman B, Liu R (2006) Motor neuron degeneration promotes neural progenitor cell proliferation, migration, and neurogenesis in the spinal cords of amyotrophic lateral sclerosis mice. Stem Cells 24:34–43. https://doi.org/10.1634/stemcells.2005-0076
Davis-Dusenbery BN, Williams LA, Klim JR, Eggan K (2014) How to make spinal motor neurons. Development 141:491–501. https://doi.org/10.1242/dev.097410
Ebrahimi-Barough S, Hoveizi E, Yazdankhah M, Ai J, Khakbiz M, Faghihi F, Tajerian R, Bayat N (2017) Inhibitor of PI3K/Akt signaling pathway small molecule promotes motor neuron differentiation of human endometrial stem cells cultured on electrospun biocomposite polycaprolactone/collagen scaffolds. Mol Neurobiol 54:2547–2554. https://doi.org/10.1007/s12035-016-9828-z
Falik Zaccai TC, Savitzki D, Zivony-Elboum Y, Vilboux T, Fitts EC, Shoval Y, Kalfon L, Samra N, Keren Z, Gross B, Chasnyk N, Straussberg R, Mullikin JC, Teer JK, Geiger D, Kornitzer D, Bitterman-Deutsch O, Samson AO, Wakamiya M, Peterson JW, Kirtley ML, Pinchuk IV, Baze WB, Gahl WA, Kleta R, Anikster Y, Chopra AK (2017) Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy. Brain 140:370–386. https://doi.org/10.1093/brain/aww295
Forman BM, Chen J, Evans RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 94:4312–4317. https://doi.org/10.1073/pnas.94.9.4312
Gaudet RJ, Alam I, Levine L (1980) Accumulation of cyclooxygenase products of arachidonic acid metabolism in gerbil brain during reperfusion after bilateral common carotid artery occlusion. J Neurochem 35:653–658. https://doi.org/10.1111/j.1471-4159.1980.tb03704.x
Goncalves MB, Williams EJ, Yip P, Yáñez-Muñoz RJ, Williams G, Doherty P (2010) The COX-2 inhibitors, meloxicam and nimesulide, suppress neurogenesis in the adult mouse brain. Br J Pharmacol 159:1118–1125. https://doi.org/10.1111/j.1476-5381.2009.00618.x
Grill M, Heinemann A, Hoefler G, Peskar BA, Schuligoi R (2008) Effect of endotoxin treatment on the expression and localization of spinal cyclooxygenase, prostaglandin synthases, and PGD2 receptors. J Neurochem 104:1345–1357. https://doi.org/10.1111/j.1471-4159.2007.05078.x
Guo W, Naujock M, Fumagalli L, Vandoorne T, Baatsen P, Boon R, Ordovás L, Patel A, Welters M, Vanwelden T, Geens N, Tricot T, Benoy V, Steyaert J, Lefebvre-Omar C, Boesmans W, Jarpe M, Sterneckert J, Wegner F, Petri S, Bohl D, Vanden Berghe P, Robberecht W, Van Damme P, Verfaillie C, Van Den Bosch L (2017) HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nat Commun 8:861. https://doi.org/10.1038/s41467-017-00911-y
Gurwitz D, Cunningham DD (1988) Thrombin modulates and reverses neuroblastoma neurite outgrowth. Proc Natl Acad Sci U S A 85:3440–3444. https://doi.org/10.1073/pnas.85.10.3440
Han SW, Greene ME, Pitts J, Wada RK, Sidell N (2001) Novel expression and function of peroxisome proliferator-activated receptor gamma (PPARϒ) in human neuroblastoma cells. Clin Cancer Res 7:98–104
Hiruma H, Ichikawa T, Kobayashi H, Hoka S, Takenaka T, Kawakami T (2000) Prostaglandin E2 enhances axonal transport and neuritogenesis in cultured mouse dorsal root ganglion neurons. Neuroscience 100:885–891. https://doi.org/10.1016/S0306-4522(00)00347-X
Ho L, Luterman JD, Aisen PS, Pasinetti GM, Montine TJ, Morrow JD (2000) Elevated CSF prostaglandin E2 levels in patients with probable AD. Neurology 55:323. https://doi.org/10.1212/WNL.55.2.323
Hounoum BM, Vourch P, Felix R, Corcia P, Patin F, Guéguinou M, Potier-Cartereau M, Vandier C, Raoul C, Andres CR, Mavel S, Blasco H (2016) NSC-34 motor neuron-like cells are unsuitable as experimental model for glutamate-mediated excitotoxicity. Front Cell Neurosci 10:1–9. https://doi.org/10.3389/fncel.2016.00118
Hu BY, Zhang SC (2009) Differentiation of spinal motor neurons from pluripotent human stem cells. Nat Protoc 4:1295–1304. https://doi.org/10.1038/nprot.2009.127
Ikuno T, Masumoto H, Yamamizu K, Yoshioka M, Minakata K, Ikeda T, Sakata R, Yamashita JK (2017) Efficient and robust differentiation of endothelial cells from human induced pluripotent stem cells via lineage control with VEGF and cyclic AMP. PLoS ONE 12:e0176238. https://doi.org/10.1371/journal.pone.0176238
Iwamoto N, Kobayashi K, Kosaka K (1989) The formation of prostaglandins in the postmortem cerebral cortex of Alzheimer-type dementia patients. J Neurol 236:80–84. https://doi.org/10.1007/BF00314401
Jaiswal MK (2017) Therapeutic opportunities and challenges of induced pluripotent stem cells-derived motor neurons for treatment of amyotrophic lateral sclerosis and motor neuron disease. Neural Regen Res 12:723–736. https://doi.org/10.4103/1673-5374.206635
Johann S, Dahm M, Kipp M, Zahn U, Beyer C (2011) Regulation of choline acetyltransferase expression by 17β-oestradiol in NSC-34 cells and in the spinal cord. J Neuroendocrinol 23:839–848. https://doi.org/10.1111/j.1365-2826.2011.02192.x
Kanakasabai S, Pestereva E, Chearwae W, Gupta SK, Ansari S, Bright JJ (2012) PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes. PLoS ONE 7:1–14. https://doi.org/10.1371/journal.pone.0050500
Kihara Y, Matsushita T, Kita Y, Uematsu S, Akira S, Kira J, Ishii S, Shimizu T (2009) Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis. Proc Natl Acad Sci 106:21807–21812. https://doi.org/10.1073/pnas.0906891106
Kim DK, Kweon KJ, Kim P, Kim HJ, Kim SS, Sohn NW, Maeng S, Shin JW (2017) Ginsenoside Rg3 improves recovery from spinal cord injury in rats via suppression of neuronal apoptosis, pro-inflammatory mediators, and microglial activation. Molecules 22:122. https://doi.org/10.3390/molecules22010122
Kim H, Zahir T, Tator CH, Shoichet MS (2011) Effects of dibutyryl cyclic-AMP on survival and neuronal differentiation of neural stem/progenitor cells transplanted into spinal cord injured rats. PLoS ONE 6:1–12. https://doi.org/10.1371/journal.pone.0021744
Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, Narumiya S (1997) Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol 122:217–224. https://doi.org/10.1038/sj.bjp.0701367
Kondo M, Shibata T, Kumagai T, Osawa T, Shibata N, Kobayashi M, Sasaki S, Iwata M, Noguchi N, Uchida K (2002) 15-Deoxy-Delta(12,14)-prostaglandin J(2): The endogenous electrophile that induces neuronal apoptosis. Proc Natl Acad Sci U S A 99:7367–7372. https://doi.org/10.1073/pnas.112212599
Lee S, Cuvillier JM, Lee B, Shen R, Lee JW, Lee SK (2012) Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs. Proc Natl Acad Sci USA 109:3383–3388. https://doi.org/10.1073/pnas.1114515109
Lee S, Lee B, Lee JW, Lee SK (2009) Retinoid signaling and Neurogenin2 function are coupled for the specification of spinal motor neurons through a chromatin modifier CBP. Neuron 62:641–654. https://doi.org/10.1016/j.neuron.2009.04.025
Lee SK, Lee B, Ruiz EC, Pfaff SL (2005) Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells. Genes Dev 19:282–294. https://doi.org/10.1101/gad.1257105
Liu H, Li W, Rose ME, Pascoe JL, Miller TM, Ahmad M, Poloyac SM, Hickey RW, Graham SH (2013a) Prostaglandin D2 toxicity in primary neurons is mediated through its bioactive cyclopentenone metabolites. Neurotoxicology 39:35–44. https://doi.org/10.1016/j.neuro.2013.08.001
Liu H, Rose ME, Miller TM, Li W, Shinde SN, Pickrell AM, Poloyac SM, Graham SH, Hickey RW (2013b) COX2-derived primary and cyclopentenone prostaglandins are increased after asphyxial cardiac arrest. Brain Res 26(1519):71–77. https://doi.org/10.1016/j.brainres.2013.04.029
Liu F, Rouault C, Guesnon M, Zhu W, Clément K, Degrelle SA, Fournier T (2020) Comparative study of PPAR γ targets in human extravillous and villous cytotrophoblasts. PPAR Res 2020:1–18. https://doi.org/10.1155/2020/9210748
Liu J, Tu H, Zhang D, Zheng H, Li YL (2012) Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells. BMC Neurosci 13:129. https://doi.org/10.1186/1471-2202-13-129
Maier O, Dahm M, Brück S, Brück S, Beyer C, Johann S (2013) Differentiated NSC-34 motoneuron-like cells as experimental model for cholinergic neurodegeneration. Neurochem Int 62:1029–1038. https://doi.org/10.1016/j.neuint.2013.03.008
Maihöfner C, Probst-Cousin S, Bergmann M, Neuhuber W, Neundörfer B, Heuss D (2003) Expression and localization of cyclooxygenase-1 and -2 in human sporadic amyotrophic lateral sclerosis. Eur J Neurosci 18:1527–1534. https://doi.org/10.1046/j.1460-9568.2003.02879.x
Mantamadiotis T, Papalexis N, Dworkin S (2012) CREB signalling in neural stem/progenitor cells: Recent developments and the implications for brain tumour biology. BioEssays 34:293–300. https://doi.org/10.1002/bies.201100133
Mattammal MB, Strong R, Lakshmi VM, Chung HD, Stephenson AH (1995) Prostaglandin H synthetase-mediated metabolism of dopamine: Implication for Parkinson’s disease. J Neurochem 64:1645–1654. https://doi.org/10.1046/j.1471-4159.1995.64041645.x
Mitani K, Sekiguchi F, Maeda T, Tanaka Y, Yoshida S, Kawabata A (2016) The prostaglandin E2/EP4 receptor/cyclic AMP/T-type Ca2+ channel pathway mediates neuritogenesis in sensory neuron-like ND7/23 cells. J Pharmacol Sci 130:177–180. https://doi.org/10.1016/j.jphs.2016.02.008
Mitra P, Brownstone RM (2012) An in vitro spinal cord slice preparation for recording from lumbar motoneurons of the adult mouse. J Neurophysiol 107:728–741. https://doi.org/10.1152/jn.00558.2011
Miyagishi H, Kosuge Y, Ishige K, Ito Y (2012) Expression of microsomal prostaglandin E synthase-1 in the spinal cord in a transgenic mouse model of amyotrophic lateral sclerosis. J Pharmacol Sci 118:225–236. https://doi.org/10.1254/jphs.11221fp
Miyagishi H, Kosuge Y, Takano A, Endo M, Nango H, Yamagata-Murayama S, Hirose D, Kano R, Tanaka Y, Ishige K, Ito Y (2017) Increased expression of 15-hydroxyprostaglandin dehydrogenase in spinal astrocytes during disease progression in a model of amyotrophic lateral sclerosis. Cell Mol Neurobiol 37:445–452. https://doi.org/10.1007/s10571-016-0377-9
Miyagishi H, Kosuge Y, Yoneoka Y, Ozone M, Endo M, Osada N, Ishige K, Kusama-Eguchi K, Ito Y (2013) Prostaglandin E2-Induced cell death is mediated by activation of EP2 receptors in motor neuron-like NSC-34 cells. J Pharmacol Sci 121:347–350. https://doi.org/10.1254/jphs.12274SC
Mohan S, Ahmad AS, Glushakov AV, Chambers C, Doré S (2012) Putative role of prostaglandin receptor in intracerebral hemorrhage. Front Neurol 3:1–17. https://doi.org/10.3389/fneur.2012.00145
Molina-Holgado E, Ortiz S, Molina-Holgado F, Guaza C (2000) Induction of COX-2 and PGE(2) biosynthesis by IL-1beta is mediated by PKC and mitogen-activated protein kinases in murine astrocytes. Br J Pharmacol 131:152–159. https://doi.org/10.1038/sj.bjp.0703557
Morizane A, Doi D, Kikuchi T, Nishimura K, Takahashi J (2011) Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells. J Neurosci Res 89:117–126. https://doi.org/10.1002/jnr.22547
Nango H, Kosuge Y, Miyagishi H, Sugawa K, Ito Y, Ishige K (2017) Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34. J Pharmacol Sci 135:64–71. https://doi.org/10.1016/j.jphs.2017.09.001
Nango H, Kosuge Y, Sato M, Shibukawa Y, Aono Y, Saigusa T, Ito Y, Ishige K (2020a) Highly efficient conversion of motor neuron-like NSC-34 cells into functional motor neurons by prostaglandin E2. Cells 9:1741. https://doi.org/10.3390/cells9071741
Nango H, Kosuge Y, Yoshimura N, Miyagishi H, Kanazawa T, Hashizaki K, Suzuki T, Ishige K (2020b) The molecular mechanisms underlying prostaglandin D2-induced neuritogenesis in motor neuron-like NSC-34 cells. Cells 9:1–16. https://doi.org/10.3390/cells9040934
Novitch BG, Wichterle H, Jessell TM, Sockanathan S (2003) A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification. Neuron 40:81–95. https://doi.org/10.1016/j.neuron.2003.08.006
O’Donnell PE, Ye XZ, DeChellis MA, Davis VM, Duan SZ, Mortensen RM, Milstone DS (2016) Lipodystrophy, diabetes and normal serum insulin in PPARγ-deficient neonatal mice. PLoS ONE 11:e0160636. https://doi.org/10.1371/journal.pone.0160636
Papadimitriou D, Le Verche V, Jacquier A, Ikiz B, Przedborski S, Re DB (2010) Inflammation in ALS and SMA: sorting out the good from the evil. Neurobiol Dis 37:493–502. https://doi.org/10.1016/j.nbd.2009.10.005
Park KS, Lee RD, Kang SK, Han SY, Park KL, Yang KH, Song YS, Park HJ, Lee YM, Yun YP, Oh KW, Kim DJ, Yun YW, Hwang SJ, Lee SE, Hong JT (2004) Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway. Exp Cell Res 297:424–433. https://doi.org/10.1016/j.yexcr.2004.03.034
Peebles RS (2019) Prostaglandins in asthma and allergic diseases. Pharmacol Ther 193:1–19. https://doi.org/10.1016/j.pharmthera.2018.08.001
Pestereva E, Kanakasabai S, Bright JJ (2012) PPARγ agonists regulate the expression of stemness and differentiation genes in brain tumour stem cells. Br J Cancer 106:1702–1712. https://doi.org/10.1038/bjc.2012.161
Peterson TS, Thebeau CN, Ajit D, Camden JM, Woods LT, Wood WG, Petris MJ, Sun GY, Erb L, Weisman GA (2013) Up-regulation and activation of the P2Y(2) nucleotide receptor mediate neurite extension in IL-1β-treated mouse primary cortical neurons. J Neurochem 125:885–896. https://doi.org/10.1111/jnc.12252
Petrozziello T, Secondo A, Tedeschi V, Esposito A, Sisalli M, Scorziello A, Di Renzo G, Annunziato L (2017) ApoSOD1 lacking dismutase activity neuroprotects motor neurons exposed to beta-methylamino-L-alanine through the Ca2+/Akt/ERK1/2 prosurvival pathway. Cell Death Differ 24:511–522. https://doi.org/10.1038/cdd.2016.154
Phillis JW, Horrocks LA, Farooqui AA (2006) Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: Their role and involvement in neurological disorders. Brain Res Rev 52:201–243. https://doi.org/10.1016/j.brainresrev.2006.02.002
Qu Q, Li D, Louis KR, Li X, Yang H, Sun Q, Crandall SR, Tsang S, Zhou J, Cox CL, Cheng J, Wang F (2014) High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1. Nat Commun 5:1–13. https://doi.org/10.1038/ncomms4449
Redensek A, Rathore KI, Berard JL, López-Vales R, Swayne LA, Bennett SA, Mohri I, Taniike M, Urade Y, David S (2011) Expression and detrimental role of hematopoietic prostaglandin D synthase in spinal cord contusion injury. Glia 59:603–614. https://doi.org/10.1002/glia.21128
Ricciotti E, Fitzgerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31:986–1000. https://doi.org/10.1161/ATVBAHA.110.207449
Sarma T, Koutsouris A, Yu JZ, Krbanjevic A, Hope TJ, Rasenick MM (2015) Activation of microtubule dynamics increases neuronal growth via the nerve growth factor (NGF)- and Gαs-mediated signaling pathways. J Biol Chem 290:10045–10056. https://doi.org/10.1074/jbc.M114.630632
Shimojo D, Onodera K, Doi-Torii Y, Ishihara Y, Hattori C, Miwa Y, Tanaka S, Okada R, Ohyama M, Shoji M, Nakanishi A, Doyu M, Okano H, Okada Y (2015) Rapid, efficient, and simple motor neuron differentiation from human pluripotent stem cells. Mol Brain 8:1–15. https://doi.org/10.1186/s13041-015-0172-4
Stifani N (2014) Motor neurons and the generation of spinal motor neuron diversity. Front Cell Neurosci 8:1–22. https://doi.org/10.3389/fncel.2014.00293
Straus DS, Glass CK (2001) Cyclopentenone prostaglandins: New insights on biological activities and cellular targets. Med Res Rev 21:185–210. https://doi.org/10.1002/med.1006
Sumimoto S, Muramatsu R, Yamashita T (2015) Thromboxane A2 stimulates neurite outgrowth in cerebral cortical neurons via mitogen activated protein kinase signaling. Brain Res 1594:46–51. https://doi.org/10.1016/j.brainres.2014.07.048
Takazawa T, Croft GF, Amoroso MW, Studer L, Wichterle H, Macdermott AB (2012) Maturation of spinal motor neurons derived from human embryonic stem cells. PLoS ONE 7:1–9. https://doi.org/10.1371/journal.pone.0040154
Tamiji J, Crawford DA (2010) Prostaglandin E2 and misoprostol induce neurite retraction in Neuro-2a cells. Biochem Biophys Res Commun 398:450–456. https://doi.org/10.1016/j.bbrc.2010.06.098
Tsuchiya H, Hohjoh H, Fujiwara Y, Sugimoto Y, Koshimizu TA (2016) Prostaglandin D2 elicits the reversible neurite retraction in hypothalamic cell line. Biochem Biophys Res Commun 470:804-810. https://doi.org/10.1016/j.bbrc.2016.01.091
Turgeon B, Meloche S (2009) Interpreting neonatal lethal phenotypes in mouse mutants: Insights into gene function and human diseases. Physiol Rev 89:1–26. https://doi.org/10.1152/physrev.00040.2007
Ushikubi F, Sugimoto Y, Ichikawa A, Narumiya S (2000) Roles of prostanoids revealed from studies using mice lacking specific prostanoid receptors. Jpn J Pharmacol 83:279–285. https://doi.org/10.1254/jjp.83.279
Valizadeh-Arshad Z, Shahbazi E, Hashemizadeh S, Moradmand A, Jangkhah M, Kiani S (2018) In vitro differentiation of neural-like cells from human embryonic stem cells by a combination of dorsomorphin, XAV, and A. Cell J 19:545–551
Wang CX, Olschowka JA, Wrathall JR (1997) Increase of interleukin-1beta mRNA and protein in the spinal cord following experimental traumatic injury in the rat. Brain Res 759:190–196. https://doi.org/10.1016/s0006-8993(97)00254-0
Wong CT, Ussyshkin N, Ahmad E, Rai-Bhogal R, Li H, Crawford DA (2016) Prostaglandin E2 promotes neural proliferation and differentiation and regulates Wnt target gene expression. J Neurosci Res 94:759–775
Yagami T, Koma H, Yamamoto Y (2016) Pathophysiological roles of cyclooxygenases and prostaglandins in the central nervous system. Mol Neurobiol 53:4754–4771. https://doi.org/10.1007/s12035-015-9355-3
Yokota C, Kaji T, Kuge Y, Inoue H, Tamaki N, Minematsu K (2004) Temporal and topographic profiles of cyclooxygenase-2 expression during 24 h of focal brain ischemia in rats. Neurosci Lett 357:219–222. https://doi.org/10.1016/j.neulet.2003.12.109
Zhang B, He L, Liu Y, Zhang J, Zeng Q, Wang S, Fan Z, Fang F, Chen L, Lv Y, Xi J, Yue W, Li Y, Pei X (2018) Prostaglandin E2 is required for BMP4-induced mesoderm differentiation of human embryonic stem cells. Stem Cell Reports 10:905–919. https://doi.org/10.1016/j.stemcr.2018.01.024
Acknowledgements
We are grateful to Dr. Neil Cashman for providing the NSC-34 cell line. We thank all the members of our laboratories for the research work. The author would like to thank Editage (www.editage.com) for English language editing. This work was funded in part by a grant to encourage and promote research projects in the School of Pharmacy, Nihon University (Y.K.), and by a Nihon University Chairman of the Board of Trustees Grant. The funding bodies had no role in the design of the study or the writing of the manuscript.
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This work was funded in part by a grant to encourage and promote research projects in the School of Pharmacy, Nihon University (Y.K.), and by a Nihon University Chairman of the Board of Trustees Grant. The funding bodies had no role in the design of the study or the writing of the manuscript.
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Nango, H., Kosuge, Y. Present State and Future Perspectives of Prostaglandins as a Differentiation Factor in Motor Neurons. Cell Mol Neurobiol 42, 2097–2108 (2022). https://doi.org/10.1007/s10571-021-01104-4
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DOI: https://doi.org/10.1007/s10571-021-01104-4