{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:51:32Z","timestamp":1788371492476,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology (MOST), Taiwan","award":["MOST 108-2321-B-002-060-MY2"],"award-info":[{"award-number":["MOST 108-2321-B-002-060-MY2"]}]},{"name":"Ministry of Science and Technology (MOST), Taiwan","award":["NSTC 113-2314-B-371-014"],"award-info":[{"award-number":["NSTC 113-2314-B-371-014"]}]},{"name":"Ministry of Science and Technology (MOST), Taiwan","award":["113-CCH-IRP-028"],"award-info":[{"award-number":["113-CCH-IRP-028"]}]},{"name":"Changhua Christian Hospital, Taiwan","award":["MOST 108-2321-B-002-060-MY2"],"award-info":[{"award-number":["MOST 108-2321-B-002-060-MY2"]}]},{"name":"Changhua Christian Hospital, Taiwan","award":["NSTC 113-2314-B-371-014"],"award-info":[{"award-number":["NSTC 113-2314-B-371-014"]}]},{"name":"Changhua Christian Hospital, Taiwan","award":["113-CCH-IRP-028"],"award-info":[{"award-number":["113-CCH-IRP-028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson\u2019s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100\u03b2 levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation.<\/jats:p>","DOI":"10.3390\/cells14151148","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T11:38:41Z","timestamp":1753443521000},"page":"1148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intranasal Mitochondrial Transplantation Restores Mitochondrial Function and Modulates Glial\u2013Neuronal Interactions in a Genetic Parkinson\u2019s Disease Model of UQCRC1 Mutation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8349-862X","authenticated-orcid":false,"given":"Jui-Chih","family":"Chang","sequence":"first","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Hsien","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yi","family":"Yeh","sequence":"additional","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9359-0606","authenticated-orcid":false,"given":"Mei-Fang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan"},{"name":"Department of Nuclear Medicine, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6753-8952","authenticated-orcid":false,"given":"Yi-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Han","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan"},{"name":"Molecular Imaging Center, National Taiwan University, Taipei 106319, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ju","family":"Chang","sequence":"additional","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8241-9654","authenticated-orcid":false,"given":"Chin-San","family":"Liu","sequence":"additional","affiliation":[{"name":"Vascular and Genomic Center, Institute of ATP, Changhua Christian Hospital, Changhua 50094, Taiwan"},{"name":"Department of Neurology, Changhua Christian Hospital, Changhua 50094, Taiwan"},{"name":"Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2174\/1570159X20666220507022701","article-title":"Nanotechnological advances for nose to brain delivery of therapeutics to improve the Parkinson therapy","volume":"21","author":"Khatri","year":"2023","journal-title":"Curr. 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