Vitamin D3 Deficiency Differentially Affects Functional and Disease Outcomes in the G93A Mouse Model of Amyotrophic Lateral Sclerosis
Identifieur interne : 001558 ( Main/Exploration ); précédent : 001557; suivant : 001559Vitamin D3 Deficiency Differentially Affects Functional and Disease Outcomes in the G93A Mouse Model of Amyotrophic Lateral Sclerosis
Auteurs : Jesse A. Solomon [Canada] ; Alexandro Gianforcaro [Canada] ; Mazen J. Hamadeh [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by motor neuron death in the central nervous system. Vitamin D supplementation increases antioxidant activity, reduces inflammation and improves motor neuron survival. We have previously demonstrated that vitamin D3 supplementation at 10× the adequate intake improves functional outcomes in a mouse model of ALS.
To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS.
At age 25 d, 102 G93A mice (56 M, 46 F) were divided into two vitamin D3 groups: 1) adequate (AI; 1 IU D3/g feed) and 2) deficient (DEF; 0.025 IU D3/g feed). At age 113 d,
During disease progression, DEF mice had 25% (P = 0.022) lower paw grip endurance AUC and 19% (P = 0.017) lower motor performance AUC vs. AI mice. Prior to disease onset (CS 2), DEF mice had 36% (P = 0.016) lower clinical score (CS) vs. AI mice. DEF mice reached CS 2 six days later vs. AI mice (P = 0.004), confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. AI mice (HR = 0.57; 95% CI: 0.38, 1.74; P = 0.002). Body weight-adjusted TA (AI: r = 0.662, P = 0.001; DEF: r = 0.622, P = 0.006) and quads (AI: r = 0.661, P = 0.001; DEF: r = 0.768; P<0.001) weights were strongly correlated with age at CS 2.
Vitamin D3 deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse.
Url:
DOI: 10.1371/journal.pone.0029354
PubMed: 22216257
PubMed Central: 3246470
Affiliations:
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Solomon</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Muscle Health Research Centre, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Muscle Health Research Centre, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Gianforcaro, Alexandro" sort="Gianforcaro, Alexandro" uniqKey="Gianforcaro A" first="Alexandro" last="Gianforcaro">Alexandro Gianforcaro</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Muscle Health Research Centre, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Muscle Health Research Centre, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Hamadeh, Mazen J" sort="Hamadeh, Mazen J" uniqKey="Hamadeh M" first="Mazen J." last="Hamadeh">Mazen J. 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Solomon</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Muscle Health Research Centre, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Muscle Health Research Centre, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Gianforcaro, Alexandro" sort="Gianforcaro, Alexandro" uniqKey="Gianforcaro A" first="Alexandro" last="Gianforcaro">Alexandro Gianforcaro</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Muscle Health Research Centre, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Muscle Health Research Centre, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Hamadeh, Mazen J" sort="Hamadeh, Mazen J" uniqKey="Hamadeh M" first="Mazen J." last="Hamadeh">Mazen J. Hamadeh</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Muscle Health Research Centre, York University, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Muscle Health Research Centre, York University, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pediatrics, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by motor neuron death in the central nervous system. Vitamin D supplementation increases antioxidant activity, reduces inflammation and improves motor neuron survival. We have previously demonstrated that vitamin D<sub>3</sub> supplementation at 10× the adequate intake improves functional outcomes in a mouse model of ALS.</p><sec><title>Objective</title><p>To determine whether vitamin D deficiency influences functional and disease outcomes in a mouse model of ALS.</p></sec><sec><title>Methods</title><p>At age 25 d, 102 G93A mice (56 M, 46 F) were divided into two vitamin D<sub>3</sub> groups: 1) adequate (AI; 1 IU D<sub>3</sub>/g feed) and 2) deficient (DEF; 0.025 IU D<sub>3</sub>/g feed). At age 113 d, <italic>tibialis anterior</italic> (TA), <italic>quadriceps</italic> (quads) and brain were harvested from 42 mice (22 M and 20 F), whereas the remaining 60 mice (34 M and 26 F) were followed to endpoint.</p></sec><sec><title>Results</title><p>During disease progression, DEF mice had 25% (P = 0.022) lower paw grip endurance AUC and 19% (P = 0.017) lower motor performance AUC vs. AI mice. Prior to disease onset (CS 2), DEF mice had 36% (P = 0.016) lower clinical score (CS) vs. AI mice. DEF mice reached CS 2 six days later vs. AI mice (P = 0.004), confirmed by a logrank test which revealed that DEF mice reached CS 2 at a 43% slower rate vs. AI mice (HR = 0.57; 95% CI: 0.38, 1.74; P = 0.002). Body weight-adjusted TA (AI: r = 0.662, P = 0.001; DEF: r = 0.622, P = 0.006) and quads (AI: r = 0.661, P = 0.001; DEF: r = 0.768; P<0.001) weights were strongly correlated with age at CS 2.</p></sec><sec><title>Conclusion</title><p>Vitamin D<sub>3</sub> deficiency improves early disease severity and delays disease onset, but reduces performance in functional outcomes following disease onset, in the high-copy G93A mouse.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Nihei, K" uniqKey="Nihei K">K Nihei</name></author><author><name sortKey="Mckee, Ac" uniqKey="Mckee A">AC McKee</name></author><author><name sortKey="Kowall, Nw" uniqKey="Kowall N">NW Kowall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zang, Dw" uniqKey="Zang D">DW Zang</name></author><author><name sortKey="Cheema, Ss" uniqKey="Cheema S">SS Cheema</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Tarnopolsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazzini, L" uniqKey="Mazzini L">L Mazzini</name></author><author><name sortKey="Balzarini, C" uniqKey="Balzarini C">C Balzarini</name></author><author><name sortKey="Colombo, R" uniqKey="Colombo R">R Colombo</name></author><author><name sortKey="Mora, G" uniqKey="Mora G">G Mora</name></author><author><name sortKey="Pastore, I" uniqKey="Pastore I">I Pastore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pongratz, D" uniqKey="Pongratz D">D Pongratz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Louwerse, Es" uniqKey="Louwerse E">ES Louwerse</name></author><author><name sortKey="Weverling, Gj" uniqKey="Weverling G">GJ Weverling</name></author><author><name sortKey="Bossuyt, Pmm" uniqKey="Bossuyt P">PMM Bossuyt</name></author><author><name sortKey="Meyjes, Fep" uniqKey="Meyjes F">FEP Meyjes</name></author><author><name sortKey="Dejong, Jmbv" uniqKey="Dejong J">JMBV Dejong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tandan, R" uniqKey="Tandan R">R Tandan</name></author><author><name sortKey="Bromberg, Mb" uniqKey="Bromberg M">MB Bromberg</name></author><author><name sortKey="Forshew, D" uniqKey="Forshew D">D Forshew</name></author><author><name sortKey="Fries, Tj" uniqKey="Fries T">TJ Fries</name></author><author><name sortKey="Badger, Gj" uniqKey="Badger G">GJ Badger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yanagihara, R" uniqKey="Yanagihara R">R Yanagihara</name></author><author><name sortKey="Garruto, Rm" uniqKey="Garruto R">RM Garruto</name></author><author><name sortKey="Gajdusek, Dc" uniqKey="Gajdusek D">DC Gajdusek</name></author><author><name sortKey="Tomita, A" uniqKey="Tomita A">A Tomita</name></author><author><name sortKey="Uchikawa, T" uniqKey="Uchikawa T">T Uchikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jaarsma, D" uniqKey="Jaarsma D">D Jaarsma</name></author><author><name sortKey="Guchelaar, Hj" uniqKey="Guchelaar H">HJ Guchelaar</name></author><author><name sortKey="Haasdijk, E" uniqKey="Haasdijk E">E Haasdijk</name></author><author><name sortKey="De Jong, Jm" uniqKey="De Jong J">JM de Jong</name></author><author><name sortKey="Holstege, Jc" uniqKey="Holstege J">JC Holstege</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poduslo, Jf" uniqKey="Poduslo J">JF Poduslo</name></author><author><name sortKey="Whelan, Sl" uniqKey="Whelan S">SL Whelan</name></author><author><name sortKey="Curran, Gl" uniqKey="Curran G">GL Curran</name></author><author><name sortKey="Wengenack, Tm" uniqKey="Wengenack T">TM Wengenack</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Birge, Sj" uniqKey="Birge S">SJ Birge</name></author><author><name sortKey="Haddad, Jg" uniqKey="Haddad J">JG Haddad</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Hamilton (Ontario)</li></settlement><orgName><li>Université McMaster</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Solomon, Jesse A" sort="Solomon, Jesse A" uniqKey="Solomon J" first="Jesse A." last="Solomon">Jesse A. Solomon</name></noRegion><name sortKey="Gianforcaro, Alexandro" sort="Gianforcaro, Alexandro" uniqKey="Gianforcaro A" first="Alexandro" last="Gianforcaro">Alexandro Gianforcaro</name><name sortKey="Gianforcaro, Alexandro" sort="Gianforcaro, Alexandro" uniqKey="Gianforcaro A" first="Alexandro" last="Gianforcaro">Alexandro Gianforcaro</name><name sortKey="Hamadeh, Mazen J" sort="Hamadeh, Mazen J" uniqKey="Hamadeh M" first="Mazen J." last="Hamadeh">Mazen J. Hamadeh</name><name sortKey="Hamadeh, Mazen J" sort="Hamadeh, Mazen J" uniqKey="Hamadeh M" first="Mazen J." last="Hamadeh">Mazen J. Hamadeh</name><name sortKey="Hamadeh, Mazen J" sort="Hamadeh, Mazen J" uniqKey="Hamadeh M" first="Mazen J." last="Hamadeh">Mazen J. Hamadeh</name><name sortKey="Solomon, Jesse A" sort="Solomon, Jesse A" uniqKey="Solomon J" first="Jesse A." last="Solomon">Jesse A. Solomon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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