{"id":"https://openalex.org/W4406598643","doi":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","title":"A theoretical model for ozone therapy in depression treatment: enhancing metabotropic glutamate signaling through controlled oxidative stress","display_name":"A theoretical model for ozone therapy in depression treatment: enhancing metabotropic glutamate signaling through controlled oxidative stress","publication_year":2025,"publication_date":"2025-01-18","ids":{"openalex":"https://openalex.org/W4406598643","doi":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","pmid":"https://pubmed.ncbi.nlm.nih.gov/40070194","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/11918475"},"language":"en","primary_location":{"id":"doi:10.4103/mgr.medgasres-d-24-00123","doi":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","is_oa":true,"landing_page_url":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","pdf_url":null,"source":{"id":"https://openalex.org/S2764726520","display_name":"Medical Gas Research","issn_l":"2045-9912","issn":["2045-9912"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","ki-jl-1","medline","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320448","host_organization_name":"Medknow","host_organization_lineage":["https://openalex.org/P4310320448","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Medknow","Wolters Kluwer"],"type":"journal"},"license":"cc-by-nc-sa","license_id":"https://openalex.org/licenses/cc-by-nc-sa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Medical Gas Research","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5062989217","display_name":"Daniele Romanello","orcid":"https://orcid.org/0000-0003-1250-5260","observed_orcids":["https://orcid.org/0000-0003-1250-5260"]},"institutions":[{"id":"https://openalex.org/I4210165969","display_name":"Ospedale San Pietro Fatebenefratelli","ror":"https://ror.org/05fccw142","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210165969"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Daniele Romanello","raw_affiliation_strings":["Internal Medicine, Ospedale San Pietro, Rome, Italy"],"raw_orcid":"https://orcid.org/0000-0003-1250-5260","affiliations":[{"raw_affiliation_string":"Internal Medicine, Ospedale San Pietro, Rome, Italy","institution_ids":["https://openalex.org/I4210165969"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5086308811","display_name":"Mauro Martinelli","orcid":"https://orcid.org/0000-0001-6178-779X","observed_orcids":["https://orcid.org/0000-0001-6178-779X"]},"institutions":[{"id":"https://openalex.org/I4210165969","display_name":"Ospedale San Pietro Fatebenefratelli","ror":"https://ror.org/05fccw142","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210165969"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Mauro Martinelli","raw_affiliation_strings":["Internal Medicine, Ospedale San Pietro, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Internal Medicine, Ospedale San Pietro, Rome, Italy","institution_ids":["https://openalex.org/I4210165969"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5062989217"],"corresponding_institution_ids":["https://openalex.org/I4210165969"],"apc_list":null,"apc_paid":null,"fwci":3.1589,"has_fulltext":true,"cited_by_count":8,"citation_normalized_percentile":{"value":0.91687931,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"15","issue":"2","first_page":"210","last_page":"211"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13365","display_name":"Medical and Biological Ozone Research","score":0.8554999828338623,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T13365","display_name":"Medical and Biological Ozone Research","score":0.8554999828338623,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11071","display_name":"Treatment of Major Depression","score":0.13660000264644623,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11337","display_name":"Tryptophan and brain disorders","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/2803","display_name":"Biological Psychiatry"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ozone-therapy","display_name":"ozone therapy","score":0.949999988079071},{"id":"https://openalex.org/keywords/depression","display_name":"depression","score":0.7279999852180481},{"id":"https://openalex.org/keywords/metabotropic-glutamate-receptors","display_name":"metabotropic glutamate receptors","score":0.9259999990463257},{"id":"https://openalex.org/keywords/mglu5","display_name":"mGlu5","score":0.9980000257492065},{"id":"https://openalex.org/keywords/oxidative-stress","display_name":"oxidative stress","score":0.8840000033378601},{"id":"https://openalex.org/keywords/glutamatergic-neurotransmission","display_name":"glutamatergic neurotransmission","score":0.949999988079071},{"id":"https://openalex.org/keywords/synaptic-plasticity","display_name":"synaptic plasticity","score":0.8209999799728394},{"id":"https://openalex.org/keywords/antidepressant-mechanism-of-action","display_name":"antidepressant mechanism","score":0.6050000190734863},{"id":"https://openalex.org/keywords/g-protein-coupled-receptors","display_name":"G protein-coupled receptors","score":0.6840000152587891},{"id":"https://openalex.org/keywords/extracellular-glutamate","display_name":"extracellular glutamate","score":0.6480000019073486},{"id":"https://openalex.org/keywords/neuromodulation","display_name":"neuromodulation","score":0.7070000171661377},{"id":"https://openalex.org/keywords/major-depressive-disorder","display_name":"major depressive disorder","score":0.49799999594688416}],"concepts":[{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.6877221465110779},{"id":"https://openalex.org/C2776867660","wikidata":"https://www.wikidata.org/wiki/Q1814941","display_name":"Depression (economics)","level":2,"score":0.6422427296638489},{"id":"https://openalex.org/C49051014","wikidata":"https://www.wikidata.org/wiki/Q2033959","display_name":"Metabotropic glutamate receptor","level":4,"score":0.6270465850830078},{"id":"https://openalex.org/C61174792","wikidata":"https://www.wikidata.org/wiki/Q420510","display_name":"Glutamate receptor","level":3,"score":0.4852980971336365},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.41413670778274536},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.38550251722335815},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.35276728868484497},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.21485593914985657},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.12215331196784973},{"id":"https://openalex.org/C162324750","wikidata":"https://www.wikidata.org/wiki/Q8134","display_name":"Economics","level":0,"score":0.0},{"id":"https://openalex.org/C139719470","wikidata":"https://www.wikidata.org/wiki/Q39680","display_name":"Macroeconomics","level":1,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"doi:10.4103/mgr.medgasres-d-24-00123","doi":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","is_oa":true,"landing_page_url":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","pdf_url":null,"source":{"id":"https://openalex.org/S2764726520","display_name":"Medical Gas Research","issn_l":"2045-9912","issn":["2045-9912"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","ki-jl-1","medline","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320448","host_organization_name":"Medknow","host_organization_lineage":["https://openalex.org/P4310320448","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Medknow","Wolters Kluwer"],"type":"journal"},"license":"cc-by-nc-sa","license_id":"https://openalex.org/licenses/cc-by-nc-sa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Medical Gas Research","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:11918475","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11918475","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11918475/pdf/MGR-15-210.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-sa","license_id":"https://openalex.org/licenses/cc-by-nc-sa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Med Gas Res","raw_type":"Text"},{"id":"pmid:40070194","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40070194","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Medical gas research","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.4103/mgr.medgasres-d-24-00123","doi":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","is_oa":true,"landing_page_url":"https://doi.org/10.4103/mgr.medgasres-d-24-00123","pdf_url":null,"source":{"id":"https://openalex.org/S2764726520","display_name":"Medical Gas Research","issn_l":"2045-9912","issn":["2045-9912"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","ki-jl-1","medline","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320448","host_organization_name":"Medknow","host_organization_lineage":["https://openalex.org/P4310320448","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Medknow","Wolters Kluwer"],"type":"journal"},"license":"cc-by-nc-sa","license_id":"https://openalex.org/licenses/cc-by-nc-sa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Medical Gas Research","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.98580002784729,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4406598643.pdf","grobid_xml":"https://content.openalex.org/works/W4406598643.grobid-xml"},"referenced_works_count":11,"referenced_works":["https://openalex.org/W1994768475","https://openalex.org/W2012827629","https://openalex.org/W2066100182","https://openalex.org/W2076542130","https://openalex.org/W2077116663","https://openalex.org/W2103863804","https://openalex.org/W2120307371","https://openalex.org/W2155162140","https://openalex.org/W3110258185","https://openalex.org/W4367670147","https://openalex.org/W4400349969"],"related_works":["https://openalex.org/W4224116256","https://openalex.org/W2296507170","https://openalex.org/W2605978316","https://openalex.org/W4412521649","https://openalex.org/W2133392512","https://openalex.org/W1994768475","https://openalex.org/W1998246469","https://openalex.org/W3181102098","https://openalex.org/W2012199810","https://openalex.org/W2365539300"],"abstract_inverted_index":{"Major":[0],"depressive":[1,221,508],"disorder":[2],"is":[3,69,572,615,663,1407,1498,1726,1762],"a":[4,25,52,83,179,199,224,233,421,460,518,526,706,780,848,857,934,984,1004,1015,1054,1063,1123,1246,1332,1378,1410,1499,1546,1608,1682],"leading":[5,1581],"cause":[6],"of":[7,22,28,85,143,217,247,303,340,360,368,390,395,427,514,575,733,757,765,790,890,931,963,967,987,1006,1040,1080,1084,1136,1155,1184,1286,1299,1382,1423,1553,1589,1597,1604,1611,1738],"disability":[8],"globally,":[9],"affecting":[10],"millions":[11],"and":[12,16,76,115,125,168,192,219,243,261,271,287,314,351,376,392,404,411,435,446,454,467,491,495,502,532,535,558,564,586,644,682,723,736,775,798,802,854,888,902,913,946,950,965,976,991,998,1024,1035,1048,1142,1157,1166,1169,1187,1191,1248,1252,1260,1269,1276,1284,1319,1324,1355,1365,1396,1400,1457,1460,1476,1486,1514,1522,1527,1562,1576,1600,1650,1668,1689,1708,1720,1731,1751,1764],"imposing":[13],"significant":[14,255],"social":[15],"economic":[17],"burdens.1":[18],"Despite":[19],"the":[20,38,48,59,64,141,146,241,264,335,358,388,393,398,425,458,477,512,603,618,642,666,755,763,766,788,885,891,904,929,961,968,1077,1134,1211,1225,1229,1282,1297,1350,1421,1483,1509,1517,1551,1586,1590,1595,1601,1616,1655,1694,1700,1736,1739,1754,1765,1771],"availability":[21],"various":[23,293],"treatments,":[24],"considerable":[26],"proportion":[27],"patients":[29],"do":[30],"not":[31,1621],"respond":[32],"adequately":[33],"to":[34,95,236,357,414,529,594,634,641,646,650,728,910,937,1017,1043,1108,1132,1162,1196,1208,1214,1218,1227,1272,1295,1301,1308,1392,1435,1444,1468,1538,1549,1582,1679,1692,1702,1716,1748],"conventional":[35,1069],"therapies,":[36],"underscoring":[37],"need":[39,1510],"for":[40,55,71,92,160,166,182,189,276,452,464,555,675,772,811,906,1058,1111,1235,1316,1363,1488,1511,1525,1626,1676,1684],"innovative":[41,553],"strategies.2":[42],"Neurobiological":[43],"research":[44,895,1323,1389],"has":[45,1699],"increasingly":[46,281],"highlighted":[47],"glutamatergic":[49,123,244,290,297,796,1428],"system":[50,67,669],"as":[51,113,178,274,383,711,752,866,1003,1014,1062,1594,1624,1638,1681,1757,1759],"promising":[53,180,994],"target":[54],"antidepressant":[56,119,277,803,1029],"interventions.1,2":[57],"Glutamate,":[58],"primary":[60],"excitatory":[61],"neurotransmitter":[62],"in":[63,257,263,268,424,443,457,481,488,507,617,654,760,814,996,1115,1127,1146,1149,1152,1201,1321,1402,1426,1466,1473,1648,1651,1706],"central":[65],"nervous":[66],"(CNS),":[68],"crucial":[70,451,463,1161],"modulating":[72,240,258,547,1427],"synaptic":[73,97,126,259,336,374,399,433,478,699,989,1033],"plasticity,":[74,375],"neurogenesis,":[75],"cognitive":[77,468],"function.":[78,469],"Metabotropic":[79],"glutamate":[80,86,137,154,304,332,361,396,548,565,693,726,737,783,830,926,974,1140,1277,1456,1574],"receptors":[81,252,342,370,386,406,439,516,545,1026,1051],"(mGluRs),":[82],"subset":[84],"receptors,":[87,307,793,1579],"have":[88,279,484,1027],"gained":[89],"particular":[90],"attention":[91],"their":[93,272],"ability":[94,1039],"modulate":[96,153,296,698,795,1454],"activity":[98,320,513,700,1034],"through":[99,148,292,300,517,701,960,1338,1385,1557,1646],"slower,":[100],"more":[101],"complex":[102],"mechanisms.":[103],"Recent":[104],"preclinical":[105,1418],"studies":[106,209,1105,1129,1151,1205,1305,1441,1533],"suggest":[107],"that":[108,130,203,211,253,705,712,847,859,880,919,956,1373,1413,1491,1569,1641],"specific":[109],"mGluR":[110,1143,1436],"subtypes,":[111],"such":[112,382,710,751,1570,1593],"mGluR2/3":[114],"mGluR5,":[116],"may":[117,152,214,230,475,524,541,799,971,1358,1376,1479,1659],"exert":[118],"effects":[120,494,1030,1099,1135],"by":[121,239,326,346,546,620,661,714,741,1031,1089,1560],"regulating":[122,1032],"neurotransmission":[124,291],"plasticity.3,4":[127],"We":[128,703,1674],"propose":[129,704],"modulated":[131,184,1563],"oxidative":[132,150,185,191,201,520,539,627,708,744,851,892,907,921,957,1008,1046,1081,1094,1137,1173,1199,1215,1239,1258,1274,1302,1335,1386,1424,1448,1469,1506,1564],"stress":[133,151,563,568,922,1047,1174,1200,1216,1240,1275,1336,1425],"could":[134,156,197,696,717,864,982,1010,1052,1096,1279,1341,1572],"enhance":[135,977,1280,1573],"extracellular":[136,673,725,782,925,973,1455],"levels,":[138,549,927],"thereby":[139],"increasing":[140],"activation":[142,339,367,426,474,756,789,930,962,1437],"mGluRs.":[144,702],"Exploring":[145,1349],"mechanisms":[147,1695],"which":[149,431,449,671,695,794,1312,1745],"output":[155,1141],"open":[157,1703,1728],"new":[158,1056,1310,1704,1766],"avenues":[159,1705],"neuromodulation,":[161],"with":[162,598,817,856,993,1224,1328,1555],"potential":[163,225,273,943,1055,1165,1505,1602,1701],"therapeutic":[164,1098,1164,1202,1540],"implications":[165,1657],"depression":[167,557,815,997,1156,1526],"other":[169,559],"CNS":[170,560],"disorders.":[171,561],"In":[172,379,588,1368],"this":[173,496,688,719,875,900,1287,1353,1370,1394,1666,1677],"context,":[174],"ozone":[175,195,212,522,715,734,812,1041,1236,1339,1374,1433,1451,1489,1520],"therapy":[176,196,213,278,523,735,813,1042,1237,1340,1375,1434,1490,1521],"emerges":[177],"technique":[181,229],"generating":[183],"stress.":[186],"Already":[187],"employed":[188],"its":[190,635,942,1398,1718],"anti-inflammatory":[193],"properties,":[194],"deliver":[198],"controlled":[200,519,707,743,920,1007,1045,1447],"pulse":[202,1095],"triggers":[204],"adaptive":[205,1178],"cellular":[206,581,683,748,878,912,1085,1102,1185,1496],"responses.":[207],"Preliminary":[208],"indicate":[210],"improve":[215],"quality":[216],"life":[218],"reduce":[220],"symptoms,":[222],"suggesting":[223],"neuromodulatory":[226,869,1583],"effect.":[227],"This":[228,939,981,1073,1092,1405,1543,1697],"thus":[231,550,1011],"offer":[232,525,1053,1377],"practical":[234,1255,1672,1721],"approach":[235,528,876,901,936,1354,1395,1698],"activating":[237,352,530,721,1383],"mGluRs":[238,249,483,531,1384],"antioxidant":[242,592,647,749,862,1086,1219,1474],"systems.":[245],"Mechanisms":[246],"mGluRs:":[248],"are":[250,407,412,440,450,881,1106,1130,1193,1206,1264,1291,1306,1442,1669,1733,1768],"G-protein-coupled":[251],"play":[254],"roles":[256],"transmission":[260,298,797],"plasticity":[262,434,990],"CNS.":[265],"Their":[266],"involvement":[267],"mood":[269,465,536],"regulation":[270,466],"targets":[275],"been":[280,485],"recognized.2,3":[282],"mGluRs,":[283,932],"specifically":[284],"mGlu1,":[285],"mGlu2/3,":[286],"mGlu5,":[288],"influence":[289,729,1480,1603],"mechanisms.3":[294],"mGlu2/3":[295,341,385,792,978,1023,1459],"primarily":[299,408],"presynaptic":[301,310,791],"inhibition":[302],"release.":[305,636],"These":[306,438],"located":[308,409],"on":[309,884,898,1076,1139,1409],"neurons,":[311,313,366],"postsynaptic":[312,365],"glial":[315,380],"cells,":[316,381],"inhibit":[317],"adenylate":[318],"cyclase":[319],"via":[321],"G":[322,415],"proteins":[323],"when":[324,570],"activated":[325,418],"glutamate,":[327,677],"reducing":[328,331],"cyclic":[329,1093],"AMP":[330],"release":[333,362,389],"into":[334],"cleft.":[337],"Additionally,":[338,1463],"modulates":[343],"ion":[344],"channels":[345,350],"inhibiting":[347],"voltage-gated":[348],"calcium":[349],"potassium":[353],"channels,":[354],"further":[355,1304,1711],"contributing":[356],"reduction":[359,1083],"1.5,6":[363],"On":[364],"these":[369,515,544,1019,1050,1113,1536,1612],"influences":[371],"signal":[372],"transduction,":[373],"neuronal":[377,436],"excitability.":[378],"astrocytes,":[384],"regulate":[387],"gliotransmitters":[391],"uptake":[394,771],"from":[397,1242,1450,1671],"cleft,":[400],"preventing":[401],"excitotoxicity.":[402],"mGlu5":[403,1025,1461],"mGlu1":[405],"postsynaptically":[410],"coupled":[413],"proteins.":[416],"When":[417],"they":[419,1634,1662],"start":[420],"cascade":[422],"resulting":[423],"protein":[428,623,826],"kinase":[429],"C,":[430],"enhances":[432],"excitability.6":[437],"heavily":[441],"involved":[442,653],"long-term":[444,447,472],"potentiation":[445],"depression,":[448,1060],"learning":[453],"memory,":[455],"particularly":[456],"hippocampus,":[459],"brain":[461,505],"region":[462],"By":[470,510,686],"facilitating":[471,769],"potentiation,":[473],"counteract":[476],"deficits":[479],"observed":[480],"depression.":[482],"also":[486],"implicated":[487],"promoting":[489,533,1036],"neurogenesis":[490],"providing":[492,551],"neuroprotective":[493,801,914],"can":[497,923,1175,1452],"help":[498],"replenish":[499],"neural":[500],"populations":[501],"restore":[503,595],"normal":[504,612],"function":[506],"states.3-6":[509],"enhancing":[511,724,787,928],"pulse,":[521,709,852],"non-pharmacological":[527,985,1333],"neuroprotection":[534],"stability.":[537],"The":[538,808,917,952,1038,1566],"stimulation":[540],"indirectly":[542,697],"activate":[543,591,651,1018,1049,1458,1577],"an":[552,573,867,1727],"pathway":[554,601],"treating":[556],"Oxidative":[562,567],"output:":[566],"occurs":[569],"there":[571,1290],"overproduction":[574],"reactive":[576,629],"oxygen":[577,630],"species,":[578],"potentially":[579,786,1580],"damaging":[580],"components":[582],"like":[583],"DNA,":[584],"proteins,":[585],"lipids.7":[587],"response,":[589],"cells":[590,1556],"defenses":[593],"redox":[596,655,684,777],"balance,":[597],"one":[599],"key":[600,1124,1500],"involving":[602],"nuclear":[604,833],"factor":[605,608,834,837],"erythroid":[606,835],"2\u2013related":[607,836],"2":[609],"(Nrf2).8":[610],"Under":[611],"conditions,":[613],"Nrf2":[614,639,662,690,722,964],"sequestered":[616],"cytoplasm":[619],"Kelch-like":[621,824],"ECH-associated":[622,825],"1,":[624],"but":[625,1710],"during":[626],"stress,":[628,745,958,1009,1470],"species-induced":[631],"modifications":[632],"lead":[633],"Once":[637],"free,":[638],"translocates":[640],"nucleus":[643],"binds":[645],"response":[648,1300,1467],"elements":[649],"genes":[652],"homeostasis.9,10":[656],"A":[657],"critical":[658,1315],"gene":[659],"regulated":[660],"SLC7A11,":[664],"encoding":[665],"cystine/glutamate":[667,767,840,969],"antiporter":[668],"Xc\u2013,":[670],"exchanges":[672],"cystine":[674,770],"intracellular":[676],"supporting":[678,776],"both":[679,1281,1322],"glutathione":[680,773],"synthesis":[681,774],"balance.7-10":[685],"upregulating":[687],"antiporter,":[689,768,970],"facilitates":[691],"increased":[692],"efflux,":[694],"provided":[713],"therapy,":[716,740,1002],"leverage":[718],"pathway,":[720],"levels":[727,750,784,975,1087,1181,1220,1278,1298],"neuromodulation.":[730,938],"Theoretical":[731],"model":[732,810,845,1412,1548,1567],"regulation:":[738],"Ozone":[739,1001],"delivering":[742],"temporarily":[746],"reduces":[747],"glutathione,":[753],"triggering":[754],"Nrf2.11":[758],"This,":[759],"turn,":[761],"stimulates":[762],"expression":[764],"homeostasis.":[778],"As":[779,1331,1614],"result,":[781],"rise,":[785],"provide":[800,983],"benefits":[804,1493],"(Figure":[805],"1).Figure":[806],"1:":[807],"theoretical":[809,1411,1547,1591],"treatment.Created":[816],"Paintbrush":[818],"(Apple":[819],"version)":[820],"Version":[821],"2.6.":[822],"Keap1:":[823],"1;":[827],"mGlu2/3R:":[828],"metabotropic":[829,1578],"receptor;":[831],"Nrf2:":[832],"2;":[838],"Xc\u2013:":[839],"antiporter;":[841],"\u03b3GCS:":[842],"\u03b3-glutamylcysteine":[843],"synthetase.This":[844],"suggests":[846,955,1372,1568],"carefully":[849],"calibrated":[850],"sub-maximal":[853],"administered":[855],"frequency":[858,1487],"allows":[860,1746],"full":[861,1090],"recovery,":[863],"serve":[865,1680],"effective":[868],"strategy.":[870],"Unlike":[871],"traditional":[872],"\u201cligand-receptor\u201d":[873],"mechanisms,":[874],"envisions":[877],"responses":[879],"tunable":[882],"based":[883,1408],"amplitude,":[886],"frequency,":[887],"intensity":[889],"signal.":[893],"Further":[894,1104,1388],"should":[896,1390,1534,1620,1635],"focus":[897],"validating":[899],"refining":[903],"parameters":[905],"impulse":[908],"delivery":[909],"optimize":[911,1393,1539],"outcomes.":[915,1481],"Discussion:":[916],"hypothesis":[918,1074],"elevate":[924],"represents":[933],"novel":[935],"discussion":[940,1688],"evaluates":[941],"implications,":[944],"challenges,":[945],"future":[947,1647,1685],"directions.":[948],"Neuromodulation":[949],"neuroprotection:":[951],"proposed":[953,1545,1658],"mechanism":[954],"mediated":[959],"upregulation":[966],"increase":[972],"receptor":[979],"activation.":[980,1144],"means":[986,1381],"boosting":[988],"neuroprotection,":[992],"applications":[995,1629],"neurodegenerative":[999,1366,1528],"diseases.":[1000],"source":[1005],"be":[1012,1160,1314,1622,1636,1714],"explored":[1013],"tool":[1016],"pathways.":[1020],"Antidepressant":[1021],"potential:":[1022],"shown":[1028],"neurogenesis.":[1037],"generate":[1044],"avenue":[1057],"treatment-resistant":[1059],"either":[1061,1342],"standalone":[1064],"or":[1065,1221,1345,1630],"complementary":[1066],"intervention":[1067],"alongside":[1068],"therapies.":[1070],"Therapeutic":[1071],"strategy:":[1072],"hinges":[1075],"careful":[1078,1512],"application":[1079],"stress\u2014sub-maximal":[1082],"followed":[1088],"recovery.":[1091],"maximize":[1097],"while":[1100,1494],"minimizing":[1101,1495],"damage.":[1103],"needed":[1107,1207,1443],"establish":[1109],"protocols":[1110,1362],"optimizing":[1112],"cycles":[1114],"clinical":[1116,1325,1403,1628,1656],"applications.":[1117,1326,1722],"Experimental":[1118,1120,1440],"validation:":[1119],"validation":[1121,1599,1645],"remains":[1122,1438],"challenge.":[1125,1501],"Initial":[1126],"vitro":[1128,1147,1649],"essential":[1131,1195],"observe":[1133],"pulses":[1138,1259,1449],"Following":[1145],"findings,":[1148],"vivo":[1150,1652],"animal":[1153],"models":[1154],"neurodegeneration":[1158],"will":[1159,1313,1713],"assess":[1163],"safety.":[1167],"Safety":[1168,1502],"calibration:":[1170],"While":[1171,1417,1654],"low":[1172],"trigger":[1176],"beneficial":[1177],"responses,":[1179],"excessive":[1180],"pose":[1182],"risks":[1183],"damage":[1186,1497,1507],"apoptosis.":[1188],"Precise":[1189],"calibration":[1190,1513],"monitoring":[1192],"therefore":[1194],"safely":[1197],"harness":[1198],"contexts.":[1203],"More":[1204],"precisely":[1209],"define":[1210,1309],"individual":[1212,1464],"susceptibility":[1213],"(linked":[1217],"genetic":[1222,1477],"predisposition)":[1223],"aim":[1226,1391,1675],"personalize":[1228],"therapy.":[1230],"However,":[1231,1585],"therapeutics":[1232],"protocol":[1233],"studied":[1234],"keeps":[1238],"far":[1241,1670],"toxicity":[1243],"level,":[1244],"allowing":[1245],"safe":[1247],"secure":[1249],"tapering.":[1250],"Quantification":[1251],"monitoring:":[1253],"For":[1254],"application,":[1256],"quantifying":[1257],"establishing":[1261],"recovery":[1262],"periods":[1263],"essential.":[1265],"Developing":[1266],"real-time":[1267],"biomarkers":[1268],"imaging":[1270],"techniques":[1271],"monitor":[1273],"precision":[1283],"feasibility":[1285],"approach.":[1288],"Currently,":[1289],"no":[1292],"standards":[1293],"available":[1294],"quantify":[1296],"stimuli;":[1303],"necessary":[1307,1715],"standards,":[1311],"ensuring":[1317],"consistency":[1318],"reliability":[1320],"Combination":[1327],"pharmacological":[1329,1356],"treatments:":[1330],"strategy,":[1334],"modulation":[1337],"stand":[1343],"alone":[1344],"complement":[1346],"existing":[1347,1523],"treatments.":[1348],"synergies":[1351],"between":[1352,1519],"agents":[1357],"facilitate":[1359],"comprehensive":[1360],"treatment":[1361],"neuropsychiatric":[1364],"conditions.":[1367],"summary,":[1369],"perspective":[1371,1544],"unique,":[1379],"non-invasive":[1380],"modulation.":[1387],"verify":[1397],"efficacy":[1399],"safety":[1401],"settings.":[1404],"study":[1406],"lacks":[1414],"experimental":[1415,1598,1644,1690],"validation.":[1416],"data":[1419],"support":[1420,1625],"role":[1422],"signaling,":[1429],"direct":[1430],"evidence":[1431,1712],"linking":[1432],"limited.":[1439],"confirm":[1445],"if":[1446],"effectively":[1453],"receptors.":[1462],"variability":[1465],"including":[1471],"differences":[1472],"capacity":[1475],"factors,":[1478],"Establishing":[1482],"precise":[1484],"dose":[1485],"maximizes":[1492],"concerns":[1503],"regarding":[1504],"underscore":[1508],"monitoring.":[1515],"Finally,":[1516],"interactions":[1518,1571],"treatments":[1524],"diseases":[1529],"remain":[1530,1663],"unexplored.":[1531],"Future":[1532],"investigate":[1535],"combinations":[1537],"protocols.":[1541],"Conclusion:":[1542],"explore":[1550],"possibility":[1552],"interacting":[1554],"signals":[1558],"generated":[1559],"targeted":[1561],"stimuli.":[1565],"efflux":[1575],"effects.":[1584],"inherent":[1587],"limitations":[1588],"model,":[1592],"lack":[1596],"unaccounted":[1605],"variables,":[1606],"necessitate":[1607],"cautious":[1609],"interpretation":[1610],"findings.":[1613],"such,":[1615],"results":[1617],"presented":[1618],"here":[1619],"taken":[1623],"immediate":[1627],"definitive":[1631],"conclusions.":[1632],"Instead,":[1633],"regarded":[1637],"preliminary":[1639],"hypotheses":[1640],"require":[1642],"rigorous":[1643],"studies.":[1653],"appear":[1660],"promising,":[1661],"speculative":[1664],"at":[1665],"stage":[1667],"applicability.":[1673],"work":[1678,1755],"foundation":[1683],"research,":[1686],"sparking":[1687],"exploration":[1691],"validate":[1693],"proposed.":[1696],"neurology":[1707],"pharmacology,":[1709],"substantiate":[1717],"relevance":[1719],"Open":[1723],"access":[1724,1729],"statement:This":[1725],"journal,":[1730],"articles":[1732],"distributed":[1734],"under":[1735,1770],"terms":[1737],"Creative":[1740],"Commons":[1741],"Attribution-NonCommercial-ShareAlike":[1742],"4.0":[1743],"License,":[1744],"others":[1747],"remix,":[1749],"tweak,":[1750],"build":[1752],"upon":[1753],"non-commercially,":[1756],"long":[1758],"appropriate":[1760],"credit":[1761],"given":[1763],"creations":[1767],"licensed":[1769],"identical":[1772],"terms.":[1773]},"counts_by_year":[{"year":2026,"cited_by_count":7},{"year":2025,"cited_by_count":1}],"updated_date":"2026-11-05T12:25:35.769452","created_date":"2025-01-20T00:00:00"}