Energetic dysfunction and iron overload in early Parkinson's disease: Two distinct mechanisms?
Identifying biomarkers reflecting cellular dysfunctions in early Parkinson's disease patients (ePD) is needed to develop targeted therapeutic strategies. We aimed to determine if cellular energetic dysfunction related to increased brain sodium concentration would be co-located to microstructura...
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| Veröffentlicht in: | Parkinsonism & related disorders 2024-07, Vol.124, p.106996, Article 106996 |
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| creator | Grimaldi, Stephan Le Troter, Arnaud El Mendili, Mohamed Mounir Dary, Hugo Azulay, Jean-Philippe Zaaraoui, Wafaa Ranjeva, Jean-Philippe Eusebio, Alexandre de Rochefort, Ludovic Guye, Maxime |
| description | Identifying biomarkers reflecting cellular dysfunctions in early Parkinson's disease patients (ePD) is needed to develop targeted therapeutic strategies. We aimed to determine if cellular energetic dysfunction related to increased brain sodium concentration would be co-located to microstructural alterations and iron deposition in ePD.
We prospectively included 12 ePD (mean disease duration 20.0 ± 10.2 months) and 13 healthy controls (HC), scanned with a 7 T 1H and 23Na MRI. Complementary voxel-based and region-based assessments were performed, the latter utilizing a high-resolution multimodal template we created (combining quantitative T1 maps (qT1), transverse relaxation rate (R2*), quantitative magnetic susceptibility mapping (QSM) images) from 200 subjects. This template allowed a precise multiparametric assessment of sodium concentration, QSM, R2*, qT1, mean diffusivity, and fractional anisotropy values. A two-sided p-value |
| doi_str_mv | 10.1016/j.parkreldis.2024.106996 |
| format | Article |
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We prospectively included 12 ePD (mean disease duration 20.0 ± 10.2 months) and 13 healthy controls (HC), scanned with a 7 T 1H and 23Na MRI. Complementary voxel-based and region-based assessments were performed, the latter utilizing a high-resolution multimodal template we created (combining quantitative T1 maps (qT1), transverse relaxation rate (R2*), quantitative magnetic susceptibility mapping (QSM) images) from 200 subjects. This template allowed a precise multiparametric assessment of sodium concentration, QSM, R2*, qT1, mean diffusivity, and fractional anisotropy values. A two-sided p-value<0.05 was considered statistically significant after the Bonferroni correction.
Relative to HC, ePD showed significantly higher sodium concentration in left Substantia nigra (SN) pars reticulata (46.13 mM ± 3.52 vs 38.60 mM ± 6.10, p = 0.038), a subpart of the SN pars compacta (SNc) and ventral tegmental area, Putamen, Globus Pallidum external, accumbens nucleus and claustrum. Significantly increased QSM and R2* values, and decreased T1 values, were limited to the Nigrosomes 1 (Nig) and right SNc (all p < 0.05). QSM values in the Nig were significantly correlated to UPDRS-III scores (r = 0.91,p < 0.001).
In ePD, brain sodium accumulation was broad and dissociated from iron accumulation. As with iron accumulation, a sodium-related pathophysiological approach could lead to identifying potential new therapeutic agents and deserves further investigation.
•Cellular energetic dysfunction and microstructural alterations dissociated in ePD.•Increased brain sodium concentration affected subcortical and brainstem structures.•Iron overload was limited to the Nigrosomes 1 and correlated with the motor score.</description><identifier>ISSN: 1353-8020</identifier><identifier>ISSN: 1873-5126</identifier><identifier>EISSN: 1873-5126</identifier><identifier>DOI: 10.1016/j.parkreldis.2024.106996</identifier><identifier>PMID: 38776725</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Biomarkers ; Life Sciences ; Multiparametric magnetic resonance imaging ; Parkinson disease ; sodium ; Synucleinopathies</subject><ispartof>Parkinsonism & related disorders, 2024-07, Vol.124, p.106996, Article 106996</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>Attribution - NonCommercial - NoDerivatives</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c353t-e065a4342f2071ce086cbfbbbbf235bf24309498b4dcc2c0dc98af0026e952303</cites><orcidid>0000-0003-0849-8213 ; 0000-0001-7466-6452</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1353802024010083$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38776725$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04727546$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Grimaldi, Stephan</creatorcontrib><creatorcontrib>Le Troter, Arnaud</creatorcontrib><creatorcontrib>El Mendili, Mohamed Mounir</creatorcontrib><creatorcontrib>Dary, Hugo</creatorcontrib><creatorcontrib>Azulay, Jean-Philippe</creatorcontrib><creatorcontrib>Zaaraoui, Wafaa</creatorcontrib><creatorcontrib>Ranjeva, Jean-Philippe</creatorcontrib><creatorcontrib>Eusebio, Alexandre</creatorcontrib><creatorcontrib>de Rochefort, Ludovic</creatorcontrib><creatorcontrib>Guye, Maxime</creatorcontrib><title>Energetic dysfunction and iron overload in early Parkinson's disease: Two distinct mechanisms?</title><title>Parkinsonism & related disorders</title><addtitle>Parkinsonism Relat Disord</addtitle><description>Identifying biomarkers reflecting cellular dysfunctions in early Parkinson's disease patients (ePD) is needed to develop targeted therapeutic strategies. We aimed to determine if cellular energetic dysfunction related to increased brain sodium concentration would be co-located to microstructural alterations and iron deposition in ePD.
We prospectively included 12 ePD (mean disease duration 20.0 ± 10.2 months) and 13 healthy controls (HC), scanned with a 7 T 1H and 23Na MRI. Complementary voxel-based and region-based assessments were performed, the latter utilizing a high-resolution multimodal template we created (combining quantitative T1 maps (qT1), transverse relaxation rate (R2*), quantitative magnetic susceptibility mapping (QSM) images) from 200 subjects. This template allowed a precise multiparametric assessment of sodium concentration, QSM, R2*, qT1, mean diffusivity, and fractional anisotropy values. A two-sided p-value<0.05 was considered statistically significant after the Bonferroni correction.
Relative to HC, ePD showed significantly higher sodium concentration in left Substantia nigra (SN) pars reticulata (46.13 mM ± 3.52 vs 38.60 mM ± 6.10, p = 0.038), a subpart of the SN pars compacta (SNc) and ventral tegmental area, Putamen, Globus Pallidum external, accumbens nucleus and claustrum. Significantly increased QSM and R2* values, and decreased T1 values, were limited to the Nigrosomes 1 (Nig) and right SNc (all p < 0.05). QSM values in the Nig were significantly correlated to UPDRS-III scores (r = 0.91,p < 0.001).
In ePD, brain sodium accumulation was broad and dissociated from iron accumulation. As with iron accumulation, a sodium-related pathophysiological approach could lead to identifying potential new therapeutic agents and deserves further investigation.
•Cellular energetic dysfunction and microstructural alterations dissociated in ePD.•Increased brain sodium concentration affected subcortical and brainstem structures.•Iron overload was limited to the Nigrosomes 1 and correlated with the motor score.</description><subject>Biomarkers</subject><subject>Life Sciences</subject><subject>Multiparametric magnetic resonance imaging</subject><subject>Parkinson disease</subject><subject>sodium</subject><subject>Synucleinopathies</subject><issn>1353-8020</issn><issn>1873-5126</issn><issn>1873-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v2zAMhoWhw_qx_YVBt7UHZ7RkyXYvQxr0Y0CA9pBdJygyvSqzpVRyUuTfV4bb7jgdJJJ4yFfgSwjNYZZDLr9vZlsd_gbsGhtnDFiRyrKu5Qdyklclz0TO5FGKueBZBQyOyWmMGwAoBfBP5JhXZSlLJk7I72uH4Q8O1tDmENudM4P1jmrXUBtS4PcYOq9T5ijq0B3oQ1K2Lnr3LdIkjzriJV09-zEZbOqnPZpH7Wzs44_P5GOru4hfXt8z8uvmerW4y5b3tz8X82Vm0heHDEEKXfCCtQzK3CBU0qzbdTot4yJdBYe6qKt10RjDDDSmrnQLwCTWgnHgZ-RimvuoO7UNttfhoLy26m6-VGMNipKVopD7PLHnE7sN_mmHcVC9jQa7Tjv0u6g4iJqJWsgRrSbUBB9jwPZ9dg5qdEJt1D8n1OiEmpxIrV9fVXbrHpv3xrfVJ-BqAjDtZW8xqGgsOoONDWgG1Xj7f5UXQ56fWA</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Grimaldi, Stephan</creator><creator>Le Troter, Arnaud</creator><creator>El Mendili, Mohamed Mounir</creator><creator>Dary, Hugo</creator><creator>Azulay, Jean-Philippe</creator><creator>Zaaraoui, Wafaa</creator><creator>Ranjeva, Jean-Philippe</creator><creator>Eusebio, Alexandre</creator><creator>de Rochefort, Ludovic</creator><creator>Guye, Maxime</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0003-0849-8213</orcidid><orcidid>https://orcid.org/0000-0001-7466-6452</orcidid></search><sort><creationdate>20240701</creationdate><title>Energetic dysfunction and iron overload in early Parkinson's disease: Two distinct mechanisms?</title><author>Grimaldi, Stephan ; Le Troter, Arnaud ; El Mendili, Mohamed Mounir ; Dary, Hugo ; Azulay, Jean-Philippe ; Zaaraoui, Wafaa ; Ranjeva, Jean-Philippe ; Eusebio, Alexandre ; de Rochefort, Ludovic ; Guye, Maxime</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-e065a4342f2071ce086cbfbbbbf235bf24309498b4dcc2c0dc98af0026e952303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomarkers</topic><topic>Life Sciences</topic><topic>Multiparametric magnetic resonance imaging</topic><topic>Parkinson disease</topic><topic>sodium</topic><topic>Synucleinopathies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grimaldi, Stephan</creatorcontrib><creatorcontrib>Le Troter, Arnaud</creatorcontrib><creatorcontrib>El Mendili, Mohamed Mounir</creatorcontrib><creatorcontrib>Dary, Hugo</creatorcontrib><creatorcontrib>Azulay, Jean-Philippe</creatorcontrib><creatorcontrib>Zaaraoui, Wafaa</creatorcontrib><creatorcontrib>Ranjeva, Jean-Philippe</creatorcontrib><creatorcontrib>Eusebio, Alexandre</creatorcontrib><creatorcontrib>de Rochefort, Ludovic</creatorcontrib><creatorcontrib>Guye, Maxime</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Parkinsonism & related disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grimaldi, Stephan</au><au>Le Troter, Arnaud</au><au>El Mendili, Mohamed Mounir</au><au>Dary, Hugo</au><au>Azulay, Jean-Philippe</au><au>Zaaraoui, Wafaa</au><au>Ranjeva, Jean-Philippe</au><au>Eusebio, Alexandre</au><au>de Rochefort, Ludovic</au><au>Guye, Maxime</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Energetic dysfunction and iron overload in early Parkinson's disease: Two distinct mechanisms?</atitle><jtitle>Parkinsonism & related disorders</jtitle><addtitle>Parkinsonism Relat Disord</addtitle><date>2024-07-01</date><risdate>2024</risdate><volume>124</volume><spage>106996</spage><pages>106996-</pages><artnum>106996</artnum><issn>1353-8020</issn><issn>1873-5126</issn><eissn>1873-5126</eissn><abstract>Identifying biomarkers reflecting cellular dysfunctions in early Parkinson's disease patients (ePD) is needed to develop targeted therapeutic strategies. We aimed to determine if cellular energetic dysfunction related to increased brain sodium concentration would be co-located to microstructural alterations and iron deposition in ePD.
We prospectively included 12 ePD (mean disease duration 20.0 ± 10.2 months) and 13 healthy controls (HC), scanned with a 7 T 1H and 23Na MRI. Complementary voxel-based and region-based assessments were performed, the latter utilizing a high-resolution multimodal template we created (combining quantitative T1 maps (qT1), transverse relaxation rate (R2*), quantitative magnetic susceptibility mapping (QSM) images) from 200 subjects. This template allowed a precise multiparametric assessment of sodium concentration, QSM, R2*, qT1, mean diffusivity, and fractional anisotropy values. A two-sided p-value<0.05 was considered statistically significant after the Bonferroni correction.
Relative to HC, ePD showed significantly higher sodium concentration in left Substantia nigra (SN) pars reticulata (46.13 mM ± 3.52 vs 38.60 mM ± 6.10, p = 0.038), a subpart of the SN pars compacta (SNc) and ventral tegmental area, Putamen, Globus Pallidum external, accumbens nucleus and claustrum. Significantly increased QSM and R2* values, and decreased T1 values, were limited to the Nigrosomes 1 (Nig) and right SNc (all p < 0.05). QSM values in the Nig were significantly correlated to UPDRS-III scores (r = 0.91,p < 0.001).
In ePD, brain sodium accumulation was broad and dissociated from iron accumulation. As with iron accumulation, a sodium-related pathophysiological approach could lead to identifying potential new therapeutic agents and deserves further investigation.
•Cellular energetic dysfunction and microstructural alterations dissociated in ePD.•Increased brain sodium concentration affected subcortical and brainstem structures.•Iron overload was limited to the Nigrosomes 1 and correlated with the motor score.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>38776725</pmid><doi>10.1016/j.parkreldis.2024.106996</doi><orcidid>https://orcid.org/0000-0003-0849-8213</orcidid><orcidid>https://orcid.org/0000-0001-7466-6452</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elsevier ScienceDirect Journals |
| subjects | Biomarkers Life Sciences Multiparametric magnetic resonance imaging Parkinson disease sodium Synucleinopathies |
| title | Energetic dysfunction and iron overload in early Parkinson's disease: Two distinct mechanisms? |
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