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In addition, the translocation of SPM synthesis and redistribution in the developing and maturating retinas remains unclear. Therefore, the expression of the SPM-synthesizing enzyme, spermine synthase (SpmS), was compared in rat retinas on postnatal days 3, 21, and 120 using immunocytochemistry, Western blot (WB), and ImageJ analyses. The anti-glutamine synthetase (GS) antibody identified glial cells, and DAPI labeled the cell nuclei. At postnatal day 3 (P3), the neonatal retina shows widespread SpmS expression throughout most neuroblast cells, but absent in the developing synaptic layers and M\u00fcller cell (MCs) processes. By day 21 (P20), SpmS becomes strongly expressed in neurons, and not in glia. On day 120 (P120), SpmS was observed in synaptic areas, with significantly less presence in neuronal soma and still none in MCs. WBs showed a decrease in SpmS expression during maturation. Therefore, glial cells do not synthesize SPM, and the accumulation of SPM in MCs found earlier suggests that glial cells take up SPM via a hypothetical high-affinity SPM transporter. In glia, SPM regulates glial connexin (Cx43) and potassium (Kir4.1) channels, being a key player in CNS diseases and aging.<\/jats:p>","DOI":"10.3390\/biom15101374","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:00:32Z","timestamp":1759132832000},"page":"1374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age-Dependent Redistribution of the Life-Important Enzyme in the Retina: Adult M\u00fcller Glial Cells\u2019 Endfeet Lack Spermine Synthase Expression"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4028-0564","authenticated-orcid":false,"given":"Astrid","family":"Zayas-Santiago","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J.","family":"Malpica-Nieves","sequence":"additional","affiliation":[{"name":"School of Chiropractic, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"},{"name":"Department of Physiology, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-5033","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Santiago","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, University of Puerto Rico-Carolina, Carolina, PR 00984, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanitza","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Rivera-Aponte","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0079-4042","authenticated-orcid":false,"given":"Miguel","family":"M\u00e9ndez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"},{"name":"Department of Natural Sciences, University of Puerto Rico, Aguadilla, PR 00603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6253-9808","authenticated-orcid":false,"given":"R\u00fcdiger W.","family":"Veh","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Zell- und Neurobiologie, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Centrum 2, Charit\u00e9platz 1, D-10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8470-9484","authenticated-orcid":false,"given":"Legier V.","family":"Rojas","sequence":"additional","affiliation":[{"name":"Department of Physiology, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serguei N.","family":"Skatchkov","sequence":"additional","affiliation":[{"name":"Department of Physiology, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"},{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayam\u00f3n, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00018-009-0165-5","article-title":"Spermine Synthase","volume":"67","author":"Pegg","year":"2010","journal-title":"Cell Mol. Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/iub.1237","article-title":"The Function of Spermine","volume":"66","author":"Pegg","year":"2014","journal-title":"IUBMB Life"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14904","DOI":"10.1074\/jbc.R116.731661","article-title":"Functions of Polyamines in Mammals","volume":"291","author":"Pegg","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1016\/j.jmb.2015.06.020","article-title":"Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell","volume":"427","author":"Campbell","year":"2015","journal-title":"J. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rieck, J., Skatchkov, S.N., Derst, C., Eaton, M.J., and Veh, R.W. (2022). Unique Chemistry, Intake, and Metabolism of Polyamines in the Central Nervous System (CNS) and Its Body. Biomolecules, 12.","DOI":"10.3390\/biom12040501"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/(SICI)1098-1136(199702)19:2<171::AID-GLIA8>3.0.CO;2-3","article-title":"Astrocytes, Not Neurons, Show Most Prominent Staining for Spermidine\/Spermine-like Immunoreactivity in Adult Rat Brain","volume":"19","author":"Laube","year":"1997","journal-title":"Glia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/(SICI)1098-1136(199807)23:3<209::AID-GLIA4>3.0.CO;2-#","article-title":"Spermine\/Spermidine Is Expressed by Retinal Glial (Muller) Cells and Controls Distinct K+ Channels of Their Membrane","volume":"23","author":"Biedermann","year":"1998","journal-title":"Glia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/(SICI)1098-1136(200007)31:1<84::AID-GLIA80>3.0.CO;2-7","article-title":"Spatial Distribution of Spermine\/Spermidine Content and K(+)-Current Rectification in Frog Retinal Glial (M\u00fcller) Cells","volume":"31","author":"Skatchkov","year":"2000","journal-title":"Glia"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"R\u00edos, D.S., Malpica-Nieves, C.J., D\u00edaz-Garc\u00eda, A., Eaton, M.J., and Skatchkov, S.N. (2023). Changes in the Localization of Polyamine Spermidine in the Rat Retina with Age. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041008"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.drudis.2013.05.017","article-title":"Agmatine: Clinical Applications after 100 Years in Translation","volume":"18","author":"Piletz","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2174\/1567202054368335","article-title":"Neuronal and glial responses to polyamines in the ischemic brain","volume":"2","author":"Takano","year":"2005","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1042\/BCJ20170007","article-title":"Agmatine: Multifunctional Arginine Metabolite and Magic Bullet in Clinical Neuroscience?","volume":"474","author":"Laube","year":"2017","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Weiss, T., Bernard, R., Laube, G., Rieck, J., Eaton, M.J., Skatchkov, S.N., and Veh, R.W. (2023). As Verified with the Aid of Biotinylated Spermine, the Brain Cannot Take up Polyamines from the Bloodstream Leaving It Solely Dependent on Local Biosynthesis. Biomolecules, 13.","DOI":"10.20944\/preprints202305.1643.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/jb\/mvj003","article-title":"Decrease in Polyamines with Aging and Their Ingestion from Food and Drink","volume":"139","author":"Nishimura","year":"2006","journal-title":"J. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.molcel.2019.08.005","article-title":"Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence","volume":"76","author":"Zhang","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"716","DOI":"10.18632\/aging.100361","article-title":"Polyamines in Aging and Disease","volume":"3","author":"Minois","year":"2011","journal-title":"Aging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/s41380-024-02861-6","article-title":"Glial Cell Deficits Are a Key Feature of Schizophrenia: Implications for Neuronal Circuit Maintenance and Histological Differentiation from Classical Neurodegeneration","volume":"30","author":"Bernstein","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1134\/S1990747816010116","article-title":"Glia and Glial Polyamines. Role in Brain Function in Health and Disease","volume":"10","author":"Skatchkov","year":"2016","journal-title":"Biochem. Mosc. Suppl. Ser. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/brain\/aww307","article-title":"Loss-of-Function Mutations in the ATP13A2\/PARK9 Gene Cause Complicated Hereditary Spastic Paraplegia (SPG78)","volume":"140","author":"Martin","year":"2017","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13827","DOI":"10.1523\/JNEUROSCI.2603-15.2015","article-title":"New Insights on Astrocyte Ion Channels: Critical for Homeostasis and Neuron-Glia Signaling","volume":"35","author":"Olsen","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eaan2788","DOI":"10.1126\/science.aan2788","article-title":"Spermidine in Health and Disease","volume":"359","author":"Madeo","year":"2018","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/s43587-022-00322-9","article-title":"Mechanisms of Spermidine-Induced Autophagy and Geroprotection","volume":"2","author":"Hofer","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41419-024-06720-8","article-title":"Reduction of Spermine Synthase Enhances Autophagy to Suppress Tau Accumulation","volume":"15","author":"Tao","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4161\/auto.26918","article-title":"Spermidine-Triggered Autophagy Ameliorates Memory during Aging","volume":"10","author":"Sigrist","year":"2014","journal-title":"Autophagy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/15548627.2016.1265193","article-title":"Spermidine Boosts Autophagy to Protect from Synapse Aging","volume":"13","author":"Bhukel","year":"2017","journal-title":"Autophagy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00726-020-02881-w","article-title":"The Involvement of Polyamine Uptake and Synthesis Pathways in the Proliferation of Neonatal Astrocytes","volume":"52","author":"Mayor","year":"2020","journal-title":"Amino Acids"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1720","DOI":"10.1038\/cddis.2015.93","article-title":"Spermidine Promotes Retinal Ganglion Cell Survival and Optic Nerve Regeneration in Adult Mice Following Optic Nerve Injury","volume":"6","author":"Noro","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/ncb1975","article-title":"Induction of Autophagy by Spermidine Promotes Longevity","volume":"11","author":"Eisenberg","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1038\/nm.4222","article-title":"Cardioprotection and Lifespan Extension by the Natural Polyamine Spermidine","volume":"22","author":"Eisenberg","year":"2016","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.phrs.2016.03.023","article-title":"Modulation of Learning and Memory by Natural Polyamines","volume":"112","author":"Guerra","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/s41556-024-01468-x","article-title":"Spermidine Is Essential for Fasting-Mediated Autophagy and Longevity","volume":"26","author":"Hofer","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_32","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). Snyder-Robinson Syndrome. GeneReviews\u00ae, University of Washington."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Murray-Stewart, T., Dunworth, M., Foley, J.R., Schwartz, C.E., and Casero, R.A. (2018). Polyamine Homeostasis in Snyder-Robinson Syndrome. Med. Sci., 6.","DOI":"10.20944\/preprints201811.0422.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1074\/jbc.M807758200","article-title":"Spermine Synthase Deficiency Leads to Deafness and a Profound Sensitivity to Alpha-Difluoromethylornithine","volume":"284","author":"Wang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tao, X., Liu, J., Diaz-Perez, Z., Foley, J.R., Stewart, T.M., Casero, R.A., and Zhai, R.G. (2023). Reduction of Spermine Synthase Suppresses Tau Accumulation Through Autophagy Modulation in Tauopathy. bioRxiv, bioRxiv:2023.03.17.533015.","DOI":"10.1101\/2023.03.17.533015"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cervetto, C., Averna, M., Vergani, L., Pedrazzi, M., Amato, S., Pelassa, S., Giuliani, S., Baldini, F., Maura, G., and Mariottini, P. (2021). Reactive Astrocytosis in a Mouse Model of Chronic Polyamine Catabolism Activation. Biomolecules, 11.","DOI":"10.3390\/biom11091274"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cervelli, M., Averna, M., Vergani, L., Pedrazzi, M., Amato, S., Fiorucci, C., Rossi, M.N., Maura, G., Mariottini, P., and Cervetto, C. (2022). The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071756"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sanayama, H., Ito, K., Ookawara, S., Uemura, T., Sakiyama, Y., Sugawara, H., Tabei, K., Igarashi, K., and Soda, K. (2023). Whole Blood Spermine\/Spermidine Ratio as a New Indicator of Sarcopenia Status in Older Adults. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051403"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sakamoto, A., Terui, Y., Igarashi, K., and Kashiwagi, K. (2023). Transient Receptor Potential Ankyrin 1 (TRPA1) Channel Mediates Acrolein Cytotoxicity in Human Lung Cancer Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411847"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Uemura, T., Matsunaga, M., Yokota, Y., Takao, K., and Furuchi, T. (2023). Inhibition of Polyamine Catabolism Reduces Cellular Senescence. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713397"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-61779-034-8_1","article-title":"Current Status of the Polyamine Research Field","volume":"720","author":"Pegg","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/glia.20652","article-title":"Complex Rectification of Muller Cell Kir Currents","volume":"56","author":"Kucheryavykh","year":"2008","journal-title":"Glia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1097\/WNR.0b013e32835aa04b","article-title":"Intracellular Polyamines Enhance Astrocytic Coupling","volume":"23","author":"Benedikt","year":"2012","journal-title":"Neuroreport"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Benedikt, J., Malpica-Nieves, C.J., Rivera, Y., M\u00e9ndez-Gonz\u00e1lez, M., Nichols, C.G., Veh, R.W., Eaton, M.J., and Skatchkov, S.N. (2022). The Polyamine Spermine Potentiates the Propagation of Negatively Charged Molecules through the Astrocytic Syncytium. Biomolecules, 12.","DOI":"10.3390\/biom12121812"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zayas-Santiago, A., Agte, S., Rivera, Y., Benedikt, J., Ulbricht, E., Karl, A., D\u00e1vila, J., Savvinov, A., Kucheryavykh, Y., and Inyushin, M. (2014). Unidirectional Photoreceptor-to-M\u00fcller Glia Coupling and Unique K+ Channel Expression in Caiman Retina. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097155"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/glia.22924","article-title":"Gap Junction Coupling Confers Isopotentiality on Astrocyte Syncytium","volume":"64","author":"Ma","year":"2016","journal-title":"Glia"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kov\u00e1cs, Z., Skatchkov, S.N., Veh, R.W., Szab\u00f3, Z., N\u00e9meth, K., Szab\u00f3, P.T., Kardos, J., and H\u00e9ja, L. (2022). Critical Role of Astrocytic Polyamine and GABA Metabolism in Epileptogenesis. Front. Cell Neurosci., 15.","DOI":"10.3389\/fncel.2021.787319"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1000312","DOI":"10.4172\/2155-6113.1000312","article-title":"Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders","volume":"5","author":"Merali","year":"2014","journal-title":"J. AIDS Clin. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Peng, K.-W., Klotz, A., Guven, A., Kapadnis, U., Ravipaty, S., Tolstikov, V., Vemulapalli, V., Rodrigues, L.O., Li, H., and Kellogg, M.D. (2024). Identification and Validation of N-Acetylputrescine in Combination with Non-Canonical Clinical Features as a Parkinson\u2019s Disease Biomarker Panel. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-60872-3"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1111\/j.1471-4159.1985.tb08724.x","article-title":"Limited Blood-Brain Barrier Transport of Polyamines","volume":"44","author":"Shin","year":"1985","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zayas-Santiago, A., Malpica-Nieves, C.J., R\u00edos, D.S., D\u00edaz-Garc\u00eda, A., V\u00e1zquez, P.N., Santiago, J.M., Rivera-Aponte, D.E., Veh, R.W., M\u00e9ndez-Gonz\u00e1lez, M., and Eaton, M. (2024). Spermidine Synthase Localization in Retinal Layers: Early Age Changes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126458"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1111\/j.1471-4159.2007.04770.x","article-title":"Cellular and Subcellular Rat Brain Spermidine Synthase Expression Patterns Suggest Region-Specific Roles for Polyamines, Including Cerebellar Pre-Synaptic Function","volume":"103","author":"Krauss","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_53","first-page":"3081","article-title":"Effect of Polyamine Depletion on Cone Photoreceptors of the Developing Rabbit Retina","volume":"43","author":"Withrow","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1021\/mp400024d","article-title":"Polyamine Transport by the Polyspecific Organic Cation Transporters OCT1, OCT2, and OCT3","volume":"10","author":"Li","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hiasa, M., Miyaji, T., Haruna, Y., Takeuchi, T., Harada, Y., Moriyama, S., Yamamoto, A., Omote, H., and Moriyama, Y. (2014). Identification of a Mammalian Vesicular Polyamine Transporter. Sci. Rep., 4.","DOI":"10.1038\/srep06836"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"98","DOI":"10.7555\/JBR.36.20220001","article-title":"ATP13A2 Protects Dopaminergic Neurons in Parkinson\u2019s Disease: From Biology to Pathology","volume":"36","author":"Dang","year":"2022","journal-title":"J. Biomed. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Malpica-Nieves, C.J., Rivera, Y., Rivera-Aponte, D.E., Phanstiel, O., Veh, R.W., Eaton, M.J., and Skatchkov, S.N. (2021). Uptake of Biotinylated Spermine in Astrocytes: Effect of Cx43 siRNA, HIV-Tat Protein and Polyamine Transport Inhibitor on Polyamine Uptake. Biomolecules, 11.","DOI":"10.3390\/biom11081187"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1042\/bj3250289","article-title":"Interactions of Polyamines with Ion Channels","volume":"325","author":"Williams","year":"1997","journal-title":"Biochem. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0022-3565(24)37721-3","article-title":"Potentiation and Inhibition of Nicotinic Acetylcholine Receptors by Spermine in the TE671 Human Muscle Cell Line","volume":"286","author":"Shao","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18779","DOI":"10.1074\/jbc.TM118.003344","article-title":"Polyamines and Potassium Channels: A 25-Year Romance","volume":"293","author":"Nichols","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8991","DOI":"10.1074\/jbc.M513429200","article-title":"Polyamines Are Potent Ligands for the Capsaicin Receptor TRPV1*","volume":"281","author":"Ahern","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e202213273","DOI":"10.1085\/jgp.202213273","article-title":"Blockade of TRPV Channels by Intracellular Spermine","volume":"155","author":"Maksaev","year":"2023","journal-title":"J. Gen. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/WNR.0000000000000746","article-title":"Polyamines Preserve Connexin 43-Mediated Gap Junctional Communication during Intracellular Hypercalcemia and Acidosis","volume":"28","author":"Kucheryavykh","year":"2017","journal-title":"Neuroreport"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1523\/JNEUROSCI.23-04-01179.2003","article-title":"Subunit-Dependent Modulation of Kainate Receptors by Extracellular Protons and Polyamines","volume":"23","author":"Mott","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1523\/JNEUROSCI.4351-10.2011","article-title":"Extracellular Spermine Exacerbates Ischemic Neuronal Injury through Sensitization of ASIC1a Channels to Extracellular Acidosis","volume":"31","author":"Duan","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0306-4522(01)00582-6","article-title":"Characterization of Acid-Sensitive Ion Channels in Freshly Isolated Rat Brain Neurons","volume":"110","author":"Bolshakov","year":"2002","journal-title":"Neuroscience"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1097\/WNR.0000000000000385","article-title":"Intracellular Spermine Prevents Acid-Induced Uncoupling of Cx43 Gap Junction Channels","volume":"26","author":"Skatchkov","year":"2015","journal-title":"Neuroreport"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"172","DOI":"10.4161\/chan.4389","article-title":"Polyamine Permeation and Rectification of Kir4.1 Channels","volume":"1","author":"Kucheryavykh","year":"2007","journal-title":"Channels"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"115299","DOI":"10.1016\/j.celrep.2025.115299","article-title":"Astrocyte Kir4.1 Expression Level Territorially Controls Excitatory Transmission in the Brain","volume":"44","author":"Tyurikova","year":"2025","journal-title":"Cell Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/0024-3205(89)90409-8","article-title":"Treatment with Polyamines Can Prevent Monosodium Glutamate Neurotoxicity in the Rat Retina","volume":"44","author":"Gilad","year":"1989","journal-title":"Life Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1023\/A:1025036532672","article-title":"Overview of the Brain Polyamine-Stress-Response: Regulation, Development, and Modulation by Lithium and Role in Cell Survival","volume":"23","author":"Gilad","year":"2003","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1002\/glia.23727","article-title":"Glia of the Human Retina","volume":"68","author":"Reichenbach","year":"2020","journal-title":"Glia"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1089\/neu.2009.1097","article-title":"Polyamine Catabolism Is Enhanced after Traumatic Brain Injury","volume":"27","author":"Zahedi","year":"2010","journal-title":"J. Neurotrauma"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0006-8993(02)02447-2","article-title":"Polyamines and Central Nervous System Injury: Spermine and Spermidine Decrease Following Transient Focal Cerebral Ischemia in Spontaneously Hypertensive Rats","volume":"938","author":"Adibhatla","year":"2002","journal-title":"Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1212\/WNL.46.5.1262","article-title":"Does Monoamine Oxidase Type B Play a Role in Dopaminergic Nerve Cell Death in Parkinson\u2019s Disease?","volume":"46","author":"Damier","year":"1996","journal-title":"Neurology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.neuint.2018.02.010","article-title":"Neuroprotective Potential of Spermidine against Rotenone Induced Parkinson\u2019s Disease in Rats","volume":"116","author":"Sharma","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev-biochem-071322-021330","article-title":"Polyamines in Parkinson\u2019s Disease: Balancing Between Neurotoxicity and Neuroprotection","volume":"92","author":"Vrijsen","year":"2023","journal-title":"Annu. Rev. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13195-019-0484-1","article-title":"Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults with Subjective Cognitive Decline (SmartAge)-Study Protocol for a Randomized Controlled Trial","volume":"11","author":"Wirth","year":"2019","journal-title":"Alzheimers Res. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"10770","DOI":"10.18632\/aging.202928","article-title":"Alzheimer\u2019s Disease as a Chronic Maladaptive Polyamine Stress Response","volume":"13","author":"Polis","year":"2021","journal-title":"Aging"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1073\/pnas.0901749106","article-title":"Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10","volume":"106","author":"Scholl","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Bang, E., Park, C., Hwangbo, H., Shim, J.-H., Leem, S.-H., Hyun, J.W., Kim, G.-Y., and Choi, Y.H. (2023). Spermidine Attenuates High Glucose-Induced Oxidative Damage in Retinal Pigment Epithelial Cells by Inhibiting Production of ROS and NF-\u03baB\/NLRP3 Inflammasome Pathway. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310550"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/jb\/mvj020","article-title":"Polyamine Modulon in Escherichia Coli: Genes Involved in the Stimulation of Cell Growth by Polyamines","volume":"139","author":"Igarashi","year":"2006","journal-title":"J. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1038\/nn.3512","article-title":"Restoring Polyamines Protects from Age-Induced Memory Impairment in an Autophagy-Dependent Manner","volume":"16","author":"Gupta","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.brainresbull.2020.08.018","article-title":"Spermidine-Induced Improvement of Memory Consolidation Involves PI3K\/Akt Signaling Pathway","volume":"164","author":"Fabbrin","year":"2020","journal-title":"Brain Res. Bull."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Makarov, V., Kucheryavykh, L., Kucheryavykh, Y., Rivera, A., Eaton, M.J., Skatchkov, S.N., and Inyushin, M. (2013). Transport Reversal during Heteroexchange: A Kinetic Study. J. Biophys., 2013.","DOI":"10.1155\/2013\/683256"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Maglione, M., Kochlamazashvili, G., Eisenberg, T., R\u00e1cz, B., Michael, E., Toppe, D., Stumpf, A., Wirth, A., Zeug, A., and M\u00fcller, F.E. (2019). Spermidine Protects from Age-Related Synaptic Alterations at Hippocampal Mossy Fiber-CA3 Synapses. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-56133-3"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1167\/iovs.10-6015","article-title":"Spermidine Alleviates Severity of Murine Experimental Autoimmune Encephalomyelitis","volume":"52","author":"Guo","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0006-8993(96)00287-9","article-title":"Accelerated Recovery Following Polyamines and Aminoguanidine Treatment after Facial Nerve Injury in Rats","volume":"724","author":"Gilad","year":"1996","journal-title":"Brain Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"102083","DOI":"10.1016\/j.npep.2020.102083","article-title":"Spermidine, an Autophagy Inducer, as a Therapeutic Strategy in Neurological Disorders","volume":"83","author":"Ghosh","year":"2020","journal-title":"Neuropeptides"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/0024-3205(76)90169-7","article-title":"Interconversion of Putrescine, Spermidine and Spermine in Goldfish and Rat Retina","volume":"19","author":"Sturman","year":"1976","journal-title":"Life Sci."},{"key":"ref_91","first-page":"1228","article-title":"Polyamine-Dependent Migration of Retinal Pigment Epithelial Cells","volume":"43","author":"Johnson","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1471-4159.2006.03721.x","article-title":"Spermidine Synthase Is Prominently Expressed in the Striatal Patch Compartment and in Putative Interneurones of the Matrix Compartment","volume":"97","author":"Krauss","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Van Veen, S., Irala, D., Sakers, K., Savage, J., S\u00e9journ\u00e9, G., Bindu, D.S., Ausloos, E., Dhondt, H., Schoonvliet, N., and den Haute, C.V. (2025). Astrocytic Polyamine Transport by ATP13A4 Tunes Excitatory Synaptic Transmission. medRxiv, medRxiv:2025.04.","DOI":"10.1101\/2025.04.04.25325117"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/glia.24327","article-title":"Genesis of a functional astrocyte syncytium in the developing mouse hippocampus","volume":"71","author":"Zhong","year":"2023","journal-title":"Glia"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Han, W., Li, H., and Chen, B. (2022). Research Progress and Potential Applications of Spermidine in Ocular Diseases. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071500"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8287","DOI":"10.1073\/pnas.0611180104","article-title":"Muller cells are living optical fibers in the vertebrate retina","volume":"104","author":"Franze","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","first-page":"247","article-title":"Live cells as optical fibers in the vertebrate retina","volume":"Volume 10","author":"Yasin","year":"2012","journal-title":"Selected Topics on Optical Fiber Technology"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:42:58Z","timestamp":1759135378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,27]]},"references-count":97,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["biom15101374"],"URL":"https:\/\/doi.org\/10.3390\/biom15101374","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,27]]}}}