Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts

L. C. Triarhou, E. H. Stotz, W. C. Low, J. Norton, Bernardino Ghetti, B. Landwehrmeyer, J. M. Palacios, J. R. Simon

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The dopamine (DA) uptake system was investigated in the mesostriatal system of normal and weaver mutant mice, which lose mesencephalic DA neurons, as well as in weaver mutants with ventral mesencephalic grafts to the striatum. Assays of [3H]DA uptake in striatal synaptosomal fractions in vitro and autoradiography of [3H]mazindol binding in brain sections were carried out in wild-type mice (+/+) and in the two hemispheres of homozygous weaver mutants (wv/wv) that had received unilateral grafts of mesencephalic cell suspensions to the right side. Net [3H]DA uptake, expressed as pmol/mg-protein/2-min, was on the average 50.6 in the striatum of wild-type mice, 7.9 in the non-grafted, and 10.1 in the transplanted striatum of weaver mutants. [3]DA uptake in wild-type mice differed significantly from both the grafted and non-grafted weaver striata (P<0.001). Paired comparisons for [3H]DA uptake between right and left sides of recipient weaver mice showed a significant side effect (P<0.02), the right side being 28-38% higher than the left side [mean of all individual (R-L)/L values]. The results of amphetamine-induced turning behavior tests were compared with the biochemical findings. Mice with grafts to the right side rotated an average of 22 turns to the left and 7 turns to the right during the five one-minute sessions; the mean value L/(L+R) was 64%. A plot of (L-R) rotations against (R-L) [3H]DA uptake gave a correlation coefficient of 0.552 (P<0.05), indicating that animals with a strong rotational bias to the left tended to have higher [3H]DA on the right. Similarly, the animals that were used for [3H]mazindol binding autoradiographic studies displayed on the average 72% rotations to the left side. In the [3H]mazindol binding data, non-grafted weaver mutants showed the severest depletion relative to wild-type in the dorsomedial and dorsolateral caudate-putamen (86% and 87%, respectively). Mice with unilateral grafts to the right side showed an increase in [3H]mazindol binding signal in the transplanted side of 40-64% (depending on dorsoventral topography) over the contralateral, non-grafted side. These findings attest to the functional effects of the grafts at the anatomical, biochemical, and behavioral levels. The parallel measurements of motor performance and DA uptake in the same animals offers an index of behavioral recovery as a function of transmitter-related activity. Furthermore, by conducting measurements of the synaptosomal DA uptake in vitro and of the binding characteristics of mazindol in brain slices by autoradiography, one has the advantage of combining the anatomical resolution of uptake site visualization with a dynamic indicator of function for DA uptake in the nerve terminal.

Original languageEnglish
Pages (from-to)1349-1358
Number of pages10
JournalNeurochemical Research
Volume19
Issue number11
DOIs
StatePublished - Nov 1994

Fingerprint

Neurologic Mutant Mice
Corpus Striatum
Grafts
Dopamine
Mazindol
Transplants
Animals
Autoradiography
Brain
Matched-Pair Analysis
Dopaminergic Neurons
Putamen
Amphetamine
Topography
Suspensions
Neurons
Transmitters
Assays
Visualization

Keywords

  • Dopamine uptake carrier system
  • mazindol binding autoradiography
  • mouse, neurological mutant
  • neostriatum
  • neural graft
  • weaver

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Cite this

Triarhou, L. C., Stotz, E. H., Low, W. C., Norton, J., Ghetti, B., Landwehrmeyer, B., ... Simon, J. R. (1994). Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts. Neurochemical Research, 19(11), 1349-1358. https://doi.org/10.1007/BF00972462

Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts. / Triarhou, L. C.; Stotz, E. H.; Low, W. C.; Norton, J.; Ghetti, Bernardino; Landwehrmeyer, B.; Palacios, J. M.; Simon, J. R.

In: Neurochemical Research, Vol. 19, No. 11, 11.1994, p. 1349-1358.

Research output: Contribution to journalArticle

Triarhou, LC, Stotz, EH, Low, WC, Norton, J, Ghetti, B, Landwehrmeyer, B, Palacios, JM & Simon, JR 1994, 'Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts', Neurochemical Research, vol. 19, no. 11, pp. 1349-1358. https://doi.org/10.1007/BF00972462
Triarhou, L. C. ; Stotz, E. H. ; Low, W. C. ; Norton, J. ; Ghetti, Bernardino ; Landwehrmeyer, B. ; Palacios, J. M. ; Simon, J. R. / Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts. In: Neurochemical Research. 1994 ; Vol. 19, No. 11. pp. 1349-1358.
@article{1c5647b801fa4f6c921a592f689ebf2f,
title = "Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts",
abstract = "The dopamine (DA) uptake system was investigated in the mesostriatal system of normal and weaver mutant mice, which lose mesencephalic DA neurons, as well as in weaver mutants with ventral mesencephalic grafts to the striatum. Assays of [3H]DA uptake in striatal synaptosomal fractions in vitro and autoradiography of [3H]mazindol binding in brain sections were carried out in wild-type mice (+/+) and in the two hemispheres of homozygous weaver mutants (wv/wv) that had received unilateral grafts of mesencephalic cell suspensions to the right side. Net [3H]DA uptake, expressed as pmol/mg-protein/2-min, was on the average 50.6 in the striatum of wild-type mice, 7.9 in the non-grafted, and 10.1 in the transplanted striatum of weaver mutants. [3]DA uptake in wild-type mice differed significantly from both the grafted and non-grafted weaver striata (P<0.001). Paired comparisons for [3H]DA uptake between right and left sides of recipient weaver mice showed a significant side effect (P<0.02), the right side being 28-38{\%} higher than the left side [mean of all individual (R-L)/L values]. The results of amphetamine-induced turning behavior tests were compared with the biochemical findings. Mice with grafts to the right side rotated an average of 22 turns to the left and 7 turns to the right during the five one-minute sessions; the mean value L/(L+R) was 64{\%}. A plot of (L-R) rotations against (R-L) [3H]DA uptake gave a correlation coefficient of 0.552 (P<0.05), indicating that animals with a strong rotational bias to the left tended to have higher [3H]DA on the right. Similarly, the animals that were used for [3H]mazindol binding autoradiographic studies displayed on the average 72{\%} rotations to the left side. In the [3H]mazindol binding data, non-grafted weaver mutants showed the severest depletion relative to wild-type in the dorsomedial and dorsolateral caudate-putamen (86{\%} and 87{\%}, respectively). Mice with unilateral grafts to the right side showed an increase in [3H]mazindol binding signal in the transplanted side of 40-64{\%} (depending on dorsoventral topography) over the contralateral, non-grafted side. These findings attest to the functional effects of the grafts at the anatomical, biochemical, and behavioral levels. The parallel measurements of motor performance and DA uptake in the same animals offers an index of behavioral recovery as a function of transmitter-related activity. Furthermore, by conducting measurements of the synaptosomal DA uptake in vitro and of the binding characteristics of mazindol in brain slices by autoradiography, one has the advantage of combining the anatomical resolution of uptake site visualization with a dynamic indicator of function for DA uptake in the nerve terminal.",
keywords = "Dopamine uptake carrier system, mazindol binding autoradiography, mouse, neurological mutant, neostriatum, neural graft, weaver",
author = "Triarhou, {L. C.} and Stotz, {E. H.} and Low, {W. C.} and J. Norton and Bernardino Ghetti and B. Landwehrmeyer and Palacios, {J. M.} and Simon, {J. R.}",
year = "1994",
month = "11",
doi = "10.1007/BF00972462",
language = "English",
volume = "19",
pages = "1349--1358",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer New York",
number = "11",

}

TY - JOUR

T1 - Studies on the striatal dopamine uptake system of weaver mutant mice and effects of ventral mesencephalic grafts

AU - Triarhou, L. C.

AU - Stotz, E. H.

AU - Low, W. C.

AU - Norton, J.

AU - Ghetti, Bernardino

AU - Landwehrmeyer, B.

AU - Palacios, J. M.

AU - Simon, J. R.

PY - 1994/11

Y1 - 1994/11

N2 - The dopamine (DA) uptake system was investigated in the mesostriatal system of normal and weaver mutant mice, which lose mesencephalic DA neurons, as well as in weaver mutants with ventral mesencephalic grafts to the striatum. Assays of [3H]DA uptake in striatal synaptosomal fractions in vitro and autoradiography of [3H]mazindol binding in brain sections were carried out in wild-type mice (+/+) and in the two hemispheres of homozygous weaver mutants (wv/wv) that had received unilateral grafts of mesencephalic cell suspensions to the right side. Net [3H]DA uptake, expressed as pmol/mg-protein/2-min, was on the average 50.6 in the striatum of wild-type mice, 7.9 in the non-grafted, and 10.1 in the transplanted striatum of weaver mutants. [3]DA uptake in wild-type mice differed significantly from both the grafted and non-grafted weaver striata (P<0.001). Paired comparisons for [3H]DA uptake between right and left sides of recipient weaver mice showed a significant side effect (P<0.02), the right side being 28-38% higher than the left side [mean of all individual (R-L)/L values]. The results of amphetamine-induced turning behavior tests were compared with the biochemical findings. Mice with grafts to the right side rotated an average of 22 turns to the left and 7 turns to the right during the five one-minute sessions; the mean value L/(L+R) was 64%. A plot of (L-R) rotations against (R-L) [3H]DA uptake gave a correlation coefficient of 0.552 (P<0.05), indicating that animals with a strong rotational bias to the left tended to have higher [3H]DA on the right. Similarly, the animals that were used for [3H]mazindol binding autoradiographic studies displayed on the average 72% rotations to the left side. In the [3H]mazindol binding data, non-grafted weaver mutants showed the severest depletion relative to wild-type in the dorsomedial and dorsolateral caudate-putamen (86% and 87%, respectively). Mice with unilateral grafts to the right side showed an increase in [3H]mazindol binding signal in the transplanted side of 40-64% (depending on dorsoventral topography) over the contralateral, non-grafted side. These findings attest to the functional effects of the grafts at the anatomical, biochemical, and behavioral levels. The parallel measurements of motor performance and DA uptake in the same animals offers an index of behavioral recovery as a function of transmitter-related activity. Furthermore, by conducting measurements of the synaptosomal DA uptake in vitro and of the binding characteristics of mazindol in brain slices by autoradiography, one has the advantage of combining the anatomical resolution of uptake site visualization with a dynamic indicator of function for DA uptake in the nerve terminal.

AB - The dopamine (DA) uptake system was investigated in the mesostriatal system of normal and weaver mutant mice, which lose mesencephalic DA neurons, as well as in weaver mutants with ventral mesencephalic grafts to the striatum. Assays of [3H]DA uptake in striatal synaptosomal fractions in vitro and autoradiography of [3H]mazindol binding in brain sections were carried out in wild-type mice (+/+) and in the two hemispheres of homozygous weaver mutants (wv/wv) that had received unilateral grafts of mesencephalic cell suspensions to the right side. Net [3H]DA uptake, expressed as pmol/mg-protein/2-min, was on the average 50.6 in the striatum of wild-type mice, 7.9 in the non-grafted, and 10.1 in the transplanted striatum of weaver mutants. [3]DA uptake in wild-type mice differed significantly from both the grafted and non-grafted weaver striata (P<0.001). Paired comparisons for [3H]DA uptake between right and left sides of recipient weaver mice showed a significant side effect (P<0.02), the right side being 28-38% higher than the left side [mean of all individual (R-L)/L values]. The results of amphetamine-induced turning behavior tests were compared with the biochemical findings. Mice with grafts to the right side rotated an average of 22 turns to the left and 7 turns to the right during the five one-minute sessions; the mean value L/(L+R) was 64%. A plot of (L-R) rotations against (R-L) [3H]DA uptake gave a correlation coefficient of 0.552 (P<0.05), indicating that animals with a strong rotational bias to the left tended to have higher [3H]DA on the right. Similarly, the animals that were used for [3H]mazindol binding autoradiographic studies displayed on the average 72% rotations to the left side. In the [3H]mazindol binding data, non-grafted weaver mutants showed the severest depletion relative to wild-type in the dorsomedial and dorsolateral caudate-putamen (86% and 87%, respectively). Mice with unilateral grafts to the right side showed an increase in [3H]mazindol binding signal in the transplanted side of 40-64% (depending on dorsoventral topography) over the contralateral, non-grafted side. These findings attest to the functional effects of the grafts at the anatomical, biochemical, and behavioral levels. The parallel measurements of motor performance and DA uptake in the same animals offers an index of behavioral recovery as a function of transmitter-related activity. Furthermore, by conducting measurements of the synaptosomal DA uptake in vitro and of the binding characteristics of mazindol in brain slices by autoradiography, one has the advantage of combining the anatomical resolution of uptake site visualization with a dynamic indicator of function for DA uptake in the nerve terminal.

KW - Dopamine uptake carrier system

KW - mazindol binding autoradiography

KW - mouse, neurological mutant

KW - neostriatum

KW - neural graft

KW - weaver

UR - http://www.scopus.com/inward/record.url?scp=0028046646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028046646&partnerID=8YFLogxK

U2 - 10.1007/BF00972462

DO - 10.1007/BF00972462

M3 - Article

C2 - 7898605

AN - SCOPUS:0028046646

VL - 19

SP - 1349

EP - 1358

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 11

ER -