Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts

P Cumming, E H Danielsen, M Vafaee, L Falborg, E Steffensen, J C Sørensen, N Gillings, D Bender, K Marthi, F Andersen, O Munk, D Smith, A Møller, A Gjedde

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

Abstract

As part of the DaNeX study, the uptake and binding of several positron emitting tracers was recorded in brain of healthy Göttingen minipigs, in minipigs with a syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs which had received intrastriatal grafts of mesencephalic neurons from fetal pigs. The specific binding of [11C]NS 2214 to catecholamine uptake sites was reduced by two thirds in striatum of the intoxicated animals, while the rate constant for the decarboxylation of [18F]fluorodopa was reduced by 50% in the intoxicated animals. Several months after grafting, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However, this apparent immunological response did not preclude the re-establishment of normal [18F]fluorodopa and [11C]NS 2214 uptake in the allografted striatum.

Original languageEnglish
Title of host publicationBRIDGE
Number of pages7
Volume103
Publication dateMay 2001
Edition5
Pages309-15
DOIs
Publication statusPublished - May 2001
SeriesActa Neurologica Scandinavica
ISSN0001-6314

Fingerprint

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine D1 Receptors
Decarboxylation
Gliosis
Dopamine D2 Receptors
Perfusion
Electrons
Oxygen
Neurons

Keywords

  • Animals
  • Antineoplastic Agents/pharmacokinetics
  • Dihydroxyphenylalanine/analogs & derivatives
  • Dopamine/pharmacokinetics
  • Graft Survival
  • Isoquinolines/pharmacokinetics
  • Parkinsonian Disorders/pathology
  • Receptors, Dopamine/analysis
  • Regional Blood Flow
  • Swine
  • Tomography, Emission-Computed
  • Visual Cortex/physiology

Cite this

Cumming, P ; Danielsen, E H ; Vafaee, M ; Falborg, L ; Steffensen, E ; Sørensen, J C ; Gillings, N ; Bender, D ; Marthi, K ; Andersen, F ; Munk, O ; Smith, D ; Møller, A ; Gjedde, A. / Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts. BRIDGE. Vol. 103 5. ed. 2001. pp. 309-15 (Acta Neurologica Scandinavica).
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title = "Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts",
abstract = "As part of the DaNeX study, the uptake and binding of several positron emitting tracers was recorded in brain of healthy G{\"o}ttingen minipigs, in minipigs with a syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs which had received intrastriatal grafts of mesencephalic neurons from fetal pigs. The specific binding of [11C]NS 2214 to catecholamine uptake sites was reduced by two thirds in striatum of the intoxicated animals, while the rate constant for the decarboxylation of [18F]fluorodopa was reduced by 50{\%} in the intoxicated animals. Several months after grafting, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However, this apparent immunological response did not preclude the re-establishment of normal [18F]fluorodopa and [11C]NS 2214 uptake in the allografted striatum.",
keywords = "Animals, Antineoplastic Agents/pharmacokinetics, Dihydroxyphenylalanine/analogs & derivatives, Dopamine/pharmacokinetics, Graft Survival, Isoquinolines/pharmacokinetics, Parkinsonian Disorders/pathology, Receptors, Dopamine/analysis, Regional Blood Flow, Swine, Tomography, Emission-Computed, Visual Cortex/physiology",
author = "P Cumming and Danielsen, {E H} and M Vafaee and L Falborg and E Steffensen and S{\o}rensen, {J C} and N Gillings and D Bender and K Marthi and F Andersen and O Munk and D Smith and A M{\o}ller and A Gjedde",
year = "2001",
month = "5",
doi = "10.1034/j.1600-0404.2001.103005309.x",
language = "English",
volume = "103",
pages = "309--15",
booktitle = "BRIDGE",
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Cumming, P, Danielsen, EH, Vafaee, M, Falborg, L, Steffensen, E, Sørensen, JC, Gillings, N, Bender, D, Marthi, K, Andersen, F, Munk, O, Smith, D, Møller, A & Gjedde, A 2001, Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts. in BRIDGE. 5 edn, vol. 103, Acta Neurologica Scandinavica, pp. 309-15. https://doi.org/10.1034/j.1600-0404.2001.103005309.x

Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts. / Cumming, P; Danielsen, E H; Vafaee, M; Falborg, L; Steffensen, E; Sørensen, J C; Gillings, N; Bender, D; Marthi, K; Andersen, F; Munk, O; Smith, D; Møller, A; Gjedde, A.

BRIDGE. Vol. 103 5. ed. 2001. p. 309-15 (Acta Neurologica Scandinavica).

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

TY - CHAP

T1 - Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts

AU - Cumming, P

AU - Danielsen, E H

AU - Vafaee, M

AU - Falborg, L

AU - Steffensen, E

AU - Sørensen, J C

AU - Gillings, N

AU - Bender, D

AU - Marthi, K

AU - Andersen, F

AU - Munk, O

AU - Smith, D

AU - Møller, A

AU - Gjedde, A

PY - 2001/5

Y1 - 2001/5

N2 - As part of the DaNeX study, the uptake and binding of several positron emitting tracers was recorded in brain of healthy Göttingen minipigs, in minipigs with a syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs which had received intrastriatal grafts of mesencephalic neurons from fetal pigs. The specific binding of [11C]NS 2214 to catecholamine uptake sites was reduced by two thirds in striatum of the intoxicated animals, while the rate constant for the decarboxylation of [18F]fluorodopa was reduced by 50% in the intoxicated animals. Several months after grafting, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However, this apparent immunological response did not preclude the re-establishment of normal [18F]fluorodopa and [11C]NS 2214 uptake in the allografted striatum.

AB - As part of the DaNeX study, the uptake and binding of several positron emitting tracers was recorded in brain of healthy Göttingen minipigs, in minipigs with a syndrome of parkinsonism due to MPTP intoxication, and in parkinsonian minipigs which had received intrastriatal grafts of mesencephalic neurons from fetal pigs. The specific binding of [11C]NS 2214 to catecholamine uptake sites was reduced by two thirds in striatum of the intoxicated animals, while the rate constant for the decarboxylation of [18F]fluorodopa was reduced by 50% in the intoxicated animals. Several months after grafting, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However, this apparent immunological response did not preclude the re-establishment of normal [18F]fluorodopa and [11C]NS 2214 uptake in the allografted striatum.

KW - Animals

KW - Antineoplastic Agents/pharmacokinetics

KW - Dihydroxyphenylalanine/analogs & derivatives

KW - Dopamine/pharmacokinetics

KW - Graft Survival

KW - Isoquinolines/pharmacokinetics

KW - Parkinsonian Disorders/pathology

KW - Receptors, Dopamine/analysis

KW - Regional Blood Flow

KW - Swine

KW - Tomography, Emission-Computed

KW - Visual Cortex/physiology

U2 - 10.1034/j.1600-0404.2001.103005309.x

DO - 10.1034/j.1600-0404.2001.103005309.x

M3 - Book chapter

VL - 103

SP - 309

EP - 315

BT - BRIDGE

ER -

Cumming P, Danielsen EH, Vafaee M, Falborg L, Steffensen E, Sørensen JC et al. Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts. In BRIDGE. 5 ed. Vol. 103. 2001. p. 309-15. (Acta Neurologica Scandinavica). https://doi.org/10.1034/j.1600-0404.2001.103005309.x