Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study
Carbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/43017 |
| Acceso en línea: | https://hdl.handle.net/10171/43017 |
| Access Level: | acceso abierto |
| Palabra clave: | Rat models Dopaminergic marker Nigro-striatal depletion [11C]-dihydrotetrabenazine (11C-DTBZ) Positron emission tomography (PET) 6-Hydroxydopamine (6-OHDA) Parkinson's disease |
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Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo studyObeso, J.A. (José A.)|||/items/dadded16-df40-45a3-9feb-7ece0fa4d520Peñuelas-Sanchez, I. (Ivan)|||/items/7022e2fa-b3b0-48ed-8d39-2020cfae85a4Marin, C. (Concepció)|||/items/94f108ca-89c5-4c5a-a9d9-a6b9e61324a9Iglesias, E. (Elena)|||/items/aed3c45d-4029-4a78-a859-88079d8b9664Ecay, M. (Margarita)|||/items/62075174-6491-4648-a96e-d724a641d353Prieto-Azcárate, E. (Elena)|||/items/98983a2a-3ce1-471b-8174-68cd47fc9fcbDelgado, M. (Mercedes)|||/items/1f968675-3d5f-4b11-a700-dff07e1d6cedCollantes, M. (María)|||/items/102ad3e7-3f57-4958-8e97-39af1c92626bJuri, C. (Carlos)|||/items/29797bd5-035a-452c-9162-c885c631f0e4Quiroga-Varela, A. (Ana)|||/items/adac2591-11fd-481d-919e-9fb4f2da7ea4Gago, B. (Belén)|||/items/8f172582-cb1a-4caf-bb24-9b11ba7638cdMolinet-Dronda, F. (Francisco)|||/items/0ed0a43f-aa92-4c47-b257-d520c043c48eRat modelsDopaminergic markerNigro-striatal depletion[11C]-dihydrotetrabenazine (11C-DTBZ)Positron emission tomography (PET)6-Hydroxydopamine (6-OHDA)Parkinson's diseaseCarbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague–Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. 11C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6 weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new 11C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). 11C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between 11C-DTBZ PET SB and striatal DAT immunostaining values (r = 0.95, p < 0.001). The data presented here indicate that 11C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat.ElsevierDadun. Depósito Académico Digital Universidad de Navarra20172017-02-2320152015-02-1220152015-02-12journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfimage/tiffimage/tiffimage/tiffimage/tiffimage/tiffimage/tiffimage/tiffhttps://hdl.handle.net/10171/43017reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/430172026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study |
| title |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study |
| spellingShingle |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study Obeso, J.A. (José A.)|||/items/dadded16-df40-45a3-9feb-7ece0fa4d520 Rat models Dopaminergic marker Nigro-striatal depletion [11C]-dihydrotetrabenazine (11C-DTBZ) Positron emission tomography (PET) 6-Hydroxydopamine (6-OHDA) Parkinson's disease |
| title_short |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study |
| title_full |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study |
| title_fullStr |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study |
| title_full_unstemmed |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study |
| title_sort |
Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study |
| dc.creator.none.fl_str_mv |
Obeso, J.A. (José A.)|||/items/dadded16-df40-45a3-9feb-7ece0fa4d520 Peñuelas-Sanchez, I. (Ivan)|||/items/7022e2fa-b3b0-48ed-8d39-2020cfae85a4 Marin, C. (Concepció)|||/items/94f108ca-89c5-4c5a-a9d9-a6b9e61324a9 Iglesias, E. (Elena)|||/items/aed3c45d-4029-4a78-a859-88079d8b9664 Ecay, M. (Margarita)|||/items/62075174-6491-4648-a96e-d724a641d353 Prieto-Azcárate, E. (Elena)|||/items/98983a2a-3ce1-471b-8174-68cd47fc9fcb Delgado, M. (Mercedes)|||/items/1f968675-3d5f-4b11-a700-dff07e1d6ced Collantes, M. (María)|||/items/102ad3e7-3f57-4958-8e97-39af1c92626b Juri, C. (Carlos)|||/items/29797bd5-035a-452c-9162-c885c631f0e4 Quiroga-Varela, A. (Ana)|||/items/adac2591-11fd-481d-919e-9fb4f2da7ea4 Gago, B. (Belén)|||/items/8f172582-cb1a-4caf-bb24-9b11ba7638cd Molinet-Dronda, F. (Francisco)|||/items/0ed0a43f-aa92-4c47-b257-d520c043c48e |
| author |
Obeso, J.A. (José A.)|||/items/dadded16-df40-45a3-9feb-7ece0fa4d520 |
| author_facet |
Obeso, J.A. (José A.)|||/items/dadded16-df40-45a3-9feb-7ece0fa4d520 Peñuelas-Sanchez, I. (Ivan)|||/items/7022e2fa-b3b0-48ed-8d39-2020cfae85a4 Marin, C. (Concepció)|||/items/94f108ca-89c5-4c5a-a9d9-a6b9e61324a9 Iglesias, E. (Elena)|||/items/aed3c45d-4029-4a78-a859-88079d8b9664 Ecay, M. (Margarita)|||/items/62075174-6491-4648-a96e-d724a641d353 Prieto-Azcárate, E. (Elena)|||/items/98983a2a-3ce1-471b-8174-68cd47fc9fcb Delgado, M. (Mercedes)|||/items/1f968675-3d5f-4b11-a700-dff07e1d6ced Collantes, M. (María)|||/items/102ad3e7-3f57-4958-8e97-39af1c92626b Juri, C. (Carlos)|||/items/29797bd5-035a-452c-9162-c885c631f0e4 Quiroga-Varela, A. (Ana)|||/items/adac2591-11fd-481d-919e-9fb4f2da7ea4 Gago, B. (Belén)|||/items/8f172582-cb1a-4caf-bb24-9b11ba7638cd Molinet-Dronda, F. (Francisco)|||/items/0ed0a43f-aa92-4c47-b257-d520c043c48e |
| author_role |
author |
| author2 |
Peñuelas-Sanchez, I. (Ivan)|||/items/7022e2fa-b3b0-48ed-8d39-2020cfae85a4 Marin, C. (Concepció)|||/items/94f108ca-89c5-4c5a-a9d9-a6b9e61324a9 Iglesias, E. (Elena)|||/items/aed3c45d-4029-4a78-a859-88079d8b9664 Ecay, M. (Margarita)|||/items/62075174-6491-4648-a96e-d724a641d353 Prieto-Azcárate, E. (Elena)|||/items/98983a2a-3ce1-471b-8174-68cd47fc9fcb Delgado, M. (Mercedes)|||/items/1f968675-3d5f-4b11-a700-dff07e1d6ced Collantes, M. (María)|||/items/102ad3e7-3f57-4958-8e97-39af1c92626b Juri, C. (Carlos)|||/items/29797bd5-035a-452c-9162-c885c631f0e4 Quiroga-Varela, A. (Ana)|||/items/adac2591-11fd-481d-919e-9fb4f2da7ea4 Gago, B. (Belén)|||/items/8f172582-cb1a-4caf-bb24-9b11ba7638cd Molinet-Dronda, F. (Francisco)|||/items/0ed0a43f-aa92-4c47-b257-d520c043c48e |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Rat models Dopaminergic marker Nigro-striatal depletion [11C]-dihydrotetrabenazine (11C-DTBZ) Positron emission tomography (PET) 6-Hydroxydopamine (6-OHDA) Parkinson's disease |
| topic |
Rat models Dopaminergic marker Nigro-striatal depletion [11C]-dihydrotetrabenazine (11C-DTBZ) Positron emission tomography (PET) 6-Hydroxydopamine (6-OHDA) Parkinson's disease |
| description |
Carbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague–Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. 11C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6 weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new 11C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). 11C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between 11C-DTBZ PET SB and striatal DAT immunostaining values (r = 0.95, p < 0.001). The data presented here indicate that 11C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-02-12 2015 2015-02-12 2017 2017-02-23 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/43017 |
| url |
https://hdl.handle.net/10171/43017 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf image/tiff image/tiff image/tiff image/tiff image/tiff image/tiff image/tiff |
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Elsevier |
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Elsevier |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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15.301603 |