{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:00:47Z","timestamp":1777953647525,"version":"3.51.4"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to a spectrum of motor and non-motor symptoms. In addition to the motor deficits serving as the primary criteria for diagnosis, mood and anxiety disorders also play a significant role in shaping the prognosis and overall disease progression in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study, our aim was to characterize the progression of anxiety-like behavioral deficits in a rat model of neurotoxicity induced by 6-hydroxydopamine (6-OHDA) and to investigate insulin-like growth factor 1 (IGF-1) potential therapeutic effects on these pathological markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Behavioral changes were evaluated in male Wistar rats at 1, 2, and 3\u202fweeks post-lesion using the elevated plus maze and dark\u2013light box tests. Anxiety-like behaviors emerged as early as week 1 post-lesion and persisted through week 3. Following 6-OHDA infusion, immunohistochemical analysis revealed a decrease in tyrosine hydroxylase (TH) immunoreactivity within the ventral tegmental area (VTA) indicating a partial lesion of the nigrostriatal dopaminergic system. As a therapeutic approach we performed the intracisternal administration of a recombinant adenoviral vector encoding IGF-1 (RAd IGF-1) one week after 6-OHDA-induced neurotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At a behavioral level, IGF-1 treatment effectively prevented anxiety-like behavior by the third week of neurotoxicity. Nevertheless, IGF-1 overexpression was not able to modulate VTA dopaminergic neuron loss. These results reveal a dissociation between the behavioral effects of IGF-1 and its impact on dopaminergic neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings emphasize time-dependent alterations in anxiety-like behavior and dopaminergic neurodegeneration. In addition, these data support the potential use of IGF-1 as a therapeutic molecule and its novel administrations for future gene transfer interventions, which will shed light on the progressive nature of neurodegenerative mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1781503","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:10:47Z","timestamp":1777911047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intracisternal IGF-1 gene delivery attenuates early anxiety-like behavior but not dopaminergic neurodegeneration in a 6-OHDA rat model of parkinsonism"],"prefix":"10.3389","volume":"18","author":[{"given":"Leandro Gabriel","family":"Champarini","sequence":"first","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Macarena Lorena","family":"Herrera","sequence":"additional","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mat\u00edas","family":"J\u00e1vega Cometto","sequence":"additional","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo del Valle","family":"Bartolozzi","sequence":"additional","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aracely Janneth","family":"Naranjo Viteri","sequence":"additional","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosana","family":"Crespo","sequence":"additional","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gast\u00f3n Diego","family":"Calfa","sequence":"additional","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia Beatriz","family":"Here\u00f1\u00fa","sequence":"additional","affiliation":[{"name":"IFEC-CONICET, Departamento de Farmacolog\u00eda Otto Orsingher, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria","place":["C\u00f3rdoba, Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.bbr.2014.02.032","article-title":"Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats","volume":"265","author":"Acevedo","year":"2014","journal-title":"Behav. 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