{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T14:50:36Z","timestamp":1767451836425,"version":"build-2065373602"},"reference-count":67,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The modulation of the brain's electrical activity for therapeutic purposes has recently gained attention, supported by the promising results obtained through the non\u2010invasive application of transcranial direct current stimulation (tDCS) in the treatment of neurodegenerative and neurological diseases. To optimize therapeutic efficacy, it is crucial to investigate the cellular and molecular effects of tDCS. This will help to identify important biomarkers, predict patient's response and develop personalized treatments. In this study, we applied direct current stimulation (DCS) to a neural cell line, using mild currents over short periods of time (0.5\u2009mA, 20\u2009min), with 24\u2010h intervals. We observed that DCS induced changes in the cellular lipidome, with transient effects observed after a single stimulation (lasting 24\u2009h) and more significant, long\u2010lasting effects (up to 72\u2009h) after repeated stimulation cycles. In neural cells, multiple DCS treatment modulated structural membrane lipids (PE, PS, PI), downregulated glycerol lipids with ether\u2010linked fatty acids and pro\u2010inflammatory lipids (ceramides and lyso\u2010glycerophospholipids) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.005). Multiple DCS sessions altered transcriptional activity by decreasing the expression of inflammatory cytokines (TNF\u2010\u03b1,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.05; IL\u20101\u03b2,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.01), while increasing the expression of neuroprotective factors such as heme oxygenase\u20101 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.0001) and brain\u2010derived neurotrophic factor (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.05), as well as proteins involved in vesicular transport (SNARE, sorting nexins and seipin and \u03b1\u2010synuclein;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.05). In addition, DCS enhanced the release of extracellular vesicles, with repeated stimulations significantly increasing the release of exosomes threefold. In conclusion, while a single electrical stimulation induces transient metabolic changes with limited phenotypic effects, repeated applications induce a broader and deeper modulation of lipid species. This may lead to a neuroprotective and neuroplasticity\u2010focussed transcriptional profile, potentially supporting the therapeutic effects of tDCS at the cellular and molecular level in patients..\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70014-fig-0012-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70014","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:48:15Z","timestamp":1739263695000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Direct Current Stimulation (\n                    <scp>DCS<\/scp>\n                    ) Modulates Lipid Metabolism and Intercellular Vesicular Trafficking in SHSY\u20105Y Cell Line: Implications for Parkinson's Disease"],"prefix":"10.1111","volume":"169","author":[{"given":"Marco","family":"Piccoli","sequence":"first","affiliation":[{"name":"Institute for Molecular and Translational Cardiology (IMTC) IRCCS Policlinico San Donato  Milan Italy"},{"name":"School of Medicine University Vita\u2010Salute San Raffaele  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5029-679X","authenticated-orcid":false,"given":"Luisa","family":"Barbato","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory IRCCS Policlinico San Donato  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natale Vincenzo","family":"Maiorana","sequence":"additional","affiliation":[{"name":"\u201cAldo Ravelli\u201d Research Centre, Department of Health Sciences University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Mingione","sequence":"additional","affiliation":[{"name":"\u201cAldo Ravelli\u201d Research Centre, Department of Health Sciences University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Raimondo","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery University of Milan\u2010Bicocca  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Ghirimoldi","sequence":"additional","affiliation":[{"name":"Biological Mass Spectrometry Lab, Department of Translational Medicine University of Piemonte Orientale  Novara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Translational Cardiology (IMTC) IRCCS Policlinico San Donato  Milan 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