Serotonergic markers in Parkinson's disease and levodopa-induced dyskinesias.
Identifieur interne : 000069 ( Main/Exploration ); précédent : 000068; suivant : 000070Serotonergic markers in Parkinson's disease and levodopa-induced dyskinesias.
Auteurs : Perdita Cheshire [Australie] ; Scott Ayton [Australie] ; Kelly L. Bertram [Australie] ; Helen Ling [Royaume-Uni] ; Abi Li [Royaume-Uni] ; Catriona Mclean [Australie] ; Glenda M. Halliday [Australie] ; Sean S. O'Sullivan [Royaume-Uni] ; Tamas Revesz [Royaume-Uni] ; David I. Finkelstein [Australie] ; Elsdon Storey [Australie] ; David R. Williams [Australie]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2015.
Abstract
Preclinical animal models implicate serotonin neurons in the pathophysiology of levodopa (l-dopa)-induced dyskinesias in Parkinson's disease (PD), but effective treatment remains elusive. We examined the relationship between serotonin and l-dopa-induced dyskinesias in a pathologically confirmed cohort of PD patients. We obtained brain tissue from 44 PD cases and 17 age-matched controls and assessed monoamine levels and the serotonin and dopamine transporters in the striatum, and the extent of dopaminergic and serotonergic cell preservation in the substantia nigra (SN) and the dorsal raphe nuclei (DRN), respectively. As expected, PD patients demonstrated a severe loss of all dopaminergic markers, including dopamine (P < 0.0001) and the dopamine transporter (P < 0.0001) in the striatum, and dopaminergic neurons (P < 0.001) in the SN, compared with controls. Marked serotonin loss was observed in the caudate (but not putamen) in PD patients compared with controls (P < 0.001), but no difference was found in the levels of the serotonin transporter in the striatum or density of serotonergic neurons in the DRN between these groups, suggesting a functional but not structural change in the serotonergic system in PD. No difference was seen in levels of serotonergic and dopaminergic markers in the striatum between PD patients with and without dyskinesias, or between cases separated according to the clinical severity of their dyskinesias. The absence of a correlation between striatal serotonin markers and the incidence and severity of l-dopa-induced dyskinesias suggests that an intact and functioning serotonergic system is not a risk factor for developing dyskinesias in PD.
DOI: 10.1002/mds.26144
PubMed: 25649148
Affiliations:
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Bertram</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine (Neuroscience), Monash University, Melbourne</wicri:regionArea><wicri:noRegion>Melbourne</wicri:noRegion></affiliation></author><author><name sortKey="Ling, Helen" sort="Ling, Helen" uniqKey="Ling H" first="Helen" last="Ling">Helen Ling</name><affiliation wicri:level="3"><nlm:affiliation>Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Reta Lila Weston Institute, Institute of Neurology, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Li, Abi" sort="Li, Abi" uniqKey="Li A" first="Abi" last="Li">Abi Li</name><affiliation wicri:level="3"><nlm:affiliation>Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Mclean, Catriona" sort="Mclean, Catriona" uniqKey="Mclean C" first="Catriona" last="Mclean">Catriona Mclean</name><affiliation wicri:level="1"><nlm:affiliation>Anatomical Pathology, Alfred Hospital, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Anatomical Pathology, Alfred Hospital, Melbourne</wicri:regionArea><wicri:noRegion>Melbourne</wicri:noRegion></affiliation></author><author><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M" last="Halliday">Glenda M. Halliday</name><affiliation wicri:level="3"><nlm:affiliation>Neuroscience Research Australia and University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Neuroscience Research Australia and University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement></placeName></affiliation></author><author><name sortKey="O Sullivan, Sean S" sort="O Sullivan, Sean S" uniqKey="O Sullivan S" first="Sean S" last="O'Sullivan">Sean S. O'Sullivan</name><affiliation wicri:level="3"><nlm:affiliation>Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Reta Lila Weston Institute, Institute of Neurology, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Revesz, Tamas" sort="Revesz, Tamas" uniqKey="Revesz T" first="Tamas" last="Revesz">Tamas Revesz</name><affiliation wicri:level="3"><nlm:affiliation>Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Finkelstein, David I" sort="Finkelstein, David I" uniqKey="Finkelstein D" first="David I" last="Finkelstein">David I. Finkelstein</name><affiliation wicri:level="1"><nlm:affiliation>The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Florey Institute of Neuroscience and Mental Health, Melbourne</wicri:regionArea><wicri:noRegion>Melbourne</wicri:noRegion></affiliation></author><author><name sortKey="Storey, Elsdon" sort="Storey, Elsdon" uniqKey="Storey E" first="Elsdon" last="Storey">Elsdon Storey</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine (Neuroscience), Monash University, Melbourne</wicri:regionArea><wicri:noRegion>Melbourne</wicri:noRegion></affiliation></author><author><name sortKey="Williams, David R" sort="Williams, David R" uniqKey="Williams D" first="David R" last="Williams">David R. Williams</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine (Neuroscience), Monash University, Melbourne</wicri:regionArea><wicri:noRegion>Melbourne</wicri:noRegion></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Preclinical animal models implicate serotonin neurons in the pathophysiology of levodopa (l-dopa)-induced dyskinesias in Parkinson's disease (PD), but effective treatment remains elusive. We examined the relationship between serotonin and l-dopa-induced dyskinesias in a pathologically confirmed cohort of PD patients. We obtained brain tissue from 44 PD cases and 17 age-matched controls and assessed monoamine levels and the serotonin and dopamine transporters in the striatum, and the extent of dopaminergic and serotonergic cell preservation in the substantia nigra (SN) and the dorsal raphe nuclei (DRN), respectively. As expected, PD patients demonstrated a severe loss of all dopaminergic markers, including dopamine (P < 0.0001) and the dopamine transporter (P < 0.0001) in the striatum, and dopaminergic neurons (P < 0.001) in the SN, compared with controls. Marked serotonin loss was observed in the caudate (but not putamen) in PD patients compared with controls (P < 0.001), but no difference was found in the levels of the serotonin transporter in the striatum or density of serotonergic neurons in the DRN between these groups, suggesting a functional but not structural change in the serotonergic system in PD. No difference was seen in levels of serotonergic and dopaminergic markers in the striatum between PD patients with and without dyskinesias, or between cases separated according to the clinical severity of their dyskinesias. The absence of a correlation between striatal serotonin markers and the incidence and severity of l-dopa-induced dyskinesias suggests that an intact and functioning serotonergic system is not a risk factor for developing dyskinesias in PD.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li><li>Sydney</li></settlement></list><tree><country name="Australie"><noRegion><name sortKey="Cheshire, Perdita" sort="Cheshire, Perdita" uniqKey="Cheshire P" first="Perdita" last="Cheshire">Perdita Cheshire</name></noRegion><name sortKey="Ayton, Scott" sort="Ayton, Scott" uniqKey="Ayton S" first="Scott" last="Ayton">Scott Ayton</name><name sortKey="Bertram, Kelly L" sort="Bertram, Kelly L" uniqKey="Bertram K" first="Kelly L" last="Bertram">Kelly L. Bertram</name><name sortKey="Finkelstein, David I" sort="Finkelstein, David I" uniqKey="Finkelstein D" first="David I" last="Finkelstein">David I. Finkelstein</name><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M" last="Halliday">Glenda M. Halliday</name><name sortKey="Mclean, Catriona" sort="Mclean, Catriona" uniqKey="Mclean C" first="Catriona" last="Mclean">Catriona Mclean</name><name sortKey="Storey, Elsdon" sort="Storey, Elsdon" uniqKey="Storey E" first="Elsdon" last="Storey">Elsdon Storey</name><name sortKey="Williams, David R" sort="Williams, David R" uniqKey="Williams D" first="David R" last="Williams">David R. Williams</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Ling, Helen" sort="Ling, Helen" uniqKey="Ling H" first="Helen" last="Ling">Helen Ling</name></region><name sortKey="Li, Abi" sort="Li, Abi" uniqKey="Li A" first="Abi" last="Li">Abi Li</name><name sortKey="O Sullivan, Sean S" sort="O Sullivan, Sean S" uniqKey="O Sullivan S" first="Sean S" last="O'Sullivan">Sean S. O'Sullivan</name><name sortKey="Revesz, Tamas" sort="Revesz, Tamas" uniqKey="Revesz T" first="Tamas" last="Revesz">Tamas Revesz</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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