Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-12-8
pubmed:abstractText
Mice lacking the dopamine transporter (DAT) display biochemical and behavioural dopaminergic hyperactivity despite dramatic alteration in dopamine homeostasis. In order to determine the anatomical and functional integrity of the dopaminergic system, we examined the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis as well as DOPA decarboxylase and vesicular monoamine transporter. TH-positive neurons in the substantia nigra were only slightly decreased (-27.6 +/- 4.5%), which can not account for the dramatic decreases in the levels of TH and dopamine that we previously observed in the striatum. TH mRNA levels were decreased by 25% in the ventral midbrain with no modification in the ratio of TH mRNA levels per cell. However, TH protein levels were decreased by 90% in the striatum and 35% in the ventral midbrain. In the striatum, many dopaminergic projections had no detectable TH, while few projections maintained regular labelling as demonstrated using electron microscopy. DOPA decarboxylase levels were not modified and vesicular transporter levels were decreased by only 28.7% which suggests that the loss of TH labelling in the striatum is not due to loss of TH projections. Interestingly, we also observed sporadic TH-positive cell bodies using immunohistochemistry and in situ hybridization in the striatum of homozygote mice, and to some extent that of wild-type animals, which raises interesting possibilities as to their potential contribution to the dopamine hyperactivity and volume transmission previously reported in these animals. In conjunction with our previous findings, these results highlight the complex regulatory mechanisms controlling TH expression at the level of mRNA, protein, activity and distribution. The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson's disease implying that blockade of DAT may be beneficial in this condition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Dopa Decarboxylase, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Plasma Membrane Transport..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Slc6a3 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase, http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Biogenic Amine Transport..., http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Monoamine Transport...
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3499-511
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10564358-Animals, pubmed-meshheading:10564358-Basal Ganglia, pubmed-meshheading:10564358-Carrier Proteins, pubmed-meshheading:10564358-Dopa Decarboxylase, pubmed-meshheading:10564358-Dopamine, pubmed-meshheading:10564358-Dopamine Plasma Membrane Transport Proteins, pubmed-meshheading:10564358-Female, pubmed-meshheading:10564358-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10564358-In Situ Hybridization, pubmed-meshheading:10564358-Male, pubmed-meshheading:10564358-Membrane Glycoproteins, pubmed-meshheading:10564358-Membrane Transport Proteins, pubmed-meshheading:10564358-Mesencephalon, pubmed-meshheading:10564358-Mice, pubmed-meshheading:10564358-Mice, Knockout, pubmed-meshheading:10564358-Microscopy, Electron, pubmed-meshheading:10564358-Nerve Tissue Proteins, pubmed-meshheading:10564358-Neurons, pubmed-meshheading:10564358-Neuropeptides, pubmed-meshheading:10564358-RNA, Messenger, pubmed-meshheading:10564358-Synaptic Transmission, pubmed-meshheading:10564358-Tyrosine 3-Monooxygenase, pubmed-meshheading:10564358-Vesicular Biogenic Amine Transport Proteins, pubmed-meshheading:10564358-Vesicular Monoamine Transport Proteins
pubmed:year
1999
pubmed:articleTitle
Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter.
pubmed:affiliation
CNRS UMR 5541, Université Bordeaux II Victor Segalen, France. mjaber@hippocrate.u-bordeaux2.fr
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't