{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:54:33Z","timestamp":1780761273613,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007801","name":"Fundaci\u00f3n S\u00e9neca","doi-asserted-by":"publisher","award":["19881\/GERM\/15"],"award-info":[{"award-number":["19881\/GERM\/15"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-106498GB-I00"],"award-info":[{"award-number":["PID2019-106498GB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RED2018-102499-T"],"award-info":[{"award-number":["RED2018-102499-T"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We analyze the 7,8-dihydroxyflavone (DHF)\/TrkB signaling activation of two main intracellular pathways, mitogen-activated protein kinase (MAPK)\/ERK and phosphatidylinositol 3 kinase (PI3K)\/AKT, in the neuroprotection of axotomized retinal ganglion cells (RGCs). Methods: Adult albino Sprague-Dawley rats received left intraorbital optic nerve transection (IONT) and were divided in two groups. One group received daily intraperitoneal DHF (5 mg\/kg) and another vehicle (1%DMSO in 0.9%NaCl) from one day before IONT until processing. Additional intact rats were employed as control (n = 4). At 1, 3 or 7 days (d) after IONT, phosphorylated (p)AKT, p-MAPK, and non-phosphorylated AKT and MAPK expression levels were analyzed in the retina by Western blotting (n = 4\/group). Radial sections were also immunodetected for the above-mentioned proteins, and for Brn3a and vimentin to identify RGCs and M\u00fcller cells (MCs), respectively (n = 3\/group). Results: IONT induced increased levels of p-MAPK and MAPK at 3d in DHF- or vehicle-treated retinas and at 7d in DHF-treated retinas. IONT induced a fast decrease in AKT in retinas treated with DHF or vehicle, with higher levels of phosphorylation in DHF-treated retinas at 7d. In intact retinas and vehicle-treated groups, no p-MAPK or MAPK expression in RGCs was observed. In DHF- treated retinas p-MAPK and MAPK were expressed in the ganglion cell layer and in the RGC nuclei 3 and 7d after IONT. AKT was observed in intact and axotomized RGCs, but the signal intensity of p-AKT was stronger in DHF-treated retinas. Finally, MCs expressed higher quantities of both MAPK and AKT at 3d in both DHF- and vehicle-treated retinas, and at 7d the phosphorylation of p-MAPK was higher in DHF-treated groups. Conclusions: Phosphorylation and increased levels of AKT and MAPK through MCs and RGCs in retinas after DHF-treatment may be responsible for the increased and long-lasting RGC protection afforded by DHF after IONT.<\/jats:p>","DOI":"10.3390\/ijms221910896","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"10896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["7,8-Dihydroxiflavone Protects Adult Rat Axotomized Retinal Ganglion Cells through MAPK\/ERK and PI3K\/AKT Activation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-9868","authenticated-orcid":false,"given":"Caridad","family":"Galindo-Romero","sequence":"first","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Campus de CC de la Salud, Universidad de Murcia e Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9352-1400","authenticated-orcid":false,"given":"Beatriz","family":"Vidal-Villegas","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Campus de CC de la Salud, Universidad de Murcia e Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"},{"name":"Servicio de Oftalmolog\u00eda, Hospital Cl\u00ednico San Carlos, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"As\u00eds-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Campus de CC de la Salud, Universidad de Murcia e Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8799-6909","authenticated-orcid":false,"given":"Fernando","family":"Lucas-Ruiz","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Campus de CC de la Salud, Universidad de Murcia e Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6770-7463","authenticated-orcid":false,"given":"Alejandro","family":"Gallego-Ortega","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Campus de CC de la Salud, Universidad de Murcia e Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-1615","authenticated-orcid":false,"given":"Manuel","family":"Vidal-Sanz","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Campus de CC de la Salud, Universidad de Murcia e Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.4103\/1673-5374.162751","article-title":"Identifying specific RGC types may shed light on their idiosyncratic responses to neuroprotection","volume":"10","year":"2015","journal-title":"Neural. 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