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Query: UMLS:C0153640 (
Cerebellum
)
1,777
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In the central nervous system, dopamine is known to play a critical role in motor and cognitive functions. Although the cerebellum plays a role in the control of movement and posture and in cognitive functions, it has not been considered to be a dopaminergic region and the dopamine present was thought to represent a precursor of noradrenaline. However, recent evidence suggests that in the cerebellum there is a small dopaminergic element, whose properties are similar to the well characterized system of striatum. In order to better understand the functional role of this system and to delineate its specific interactions within the cerebellum, the distribution and properties of
dopamine transporter
(
DAT
) in the cerebellum of reeler and Purkinje cell degeneration (Nna1pcd) mutant mice, which are characterized by severe loss of different cell populations and abnormalities in synapse formation, have been studied. Kinetic studies revealed that [3H]dopamine is transported into cerebellar synaptosomes prepared from normal mice with affinities similar to that into striatal synaptosomes but with much lower maximal velocities. In reeler cerebellar synaptosomes the number of transport sites is significantly reduced. In Nna1pcd cerebellar synaptosomes the kinetic properties of transport of [3H]dopamine are similar to the normal. However, in vitro quantitative
DAT
autoradiography revealed a significantly increased binding in cerebellar nuclei, a decreased binding in molecular layer and an unaltered binding in the granule cell layer. These observations confirm a dopaminergic innervation of the cerebellum and contribute to our understanding of the intracerebellar distribution of the dopaminergic system.
Cerebellum
2005
PMID:Dopamine transporters in the cerebellum of mutant mice. 1603 92
We studied the binding parameters, the pharmacological profile and the anatomical distribution of the
dopamine transporter
in the mouse cerebellum by using the specific dopamine uptake antagonist [(3)H]GBR12935 and an antidopamine transporter monoclonal antibody. Competition experiments in cerebellar and striatal membrane preparations showed that [(3)H]GBR12935 binds to a specific binding site, sensitive to dopamine and low concentrations of mazindol. The affinity of dopamine for the cerebellar binding site was one order of magnitude lower than the affinity for the striatal binding site. Saturation experiments in cerebellar membrane preparations and thin frozen sections showed that the affinity of [(3)H]GBR12935 for this binding site is similar to its affinity for the striatal
dopamine transporter
. Saturable binding was lobule specific and in general was higher in the molecular layer compared to the granule cell layer. The immunohistochemical signal was mostly concentrated in the Purkinje cell layer and the cerebellar nuclei. The results suggest that the cerebellar
dopamine transporter
is similar but not identical to the striatal
dopamine transporter
and that it is present in the mouse cerebellum in a lobule and lamina specific pattern.
Cerebellum
2008
PMID:Pharmacological characterization and anatomical distribution of the dopamine transporter in the mouse cerebellum. 1841 65
Purpose:
The density of the neuronal
dopamine transporter
(
DAT
) is directly correlated with the presynaptic dopaminergic system injury. In a first study, we evaluated the brain distribution and kinetics of [
18
F]LBT-999, a
DAT
PET radioligand, in a group of eight healthy subjects. Taking into account the results obtained in healthy volunteers, we wanted to evaluate whether the loss of presynaptic striatal dopaminergic fibers could be estimated, under routine clinical conditions, using [
18
F]LBT-999 and a short PET acquisition.
Materials and methods:
Six patients with Parkinson's disease (PD) were compared with eight controls. Eighty-nine minutes of dynamic PET following an intravenous injection of [
18
F]LBT-999 were acquired. Using regions of interest for striatal nuclei, substantia nigra (SN), cerebellum, and occipital cortex, defined over each T1 3D MRI, time-activity curves (TACs) were obtained. From TACs, binding potential (BP
ND
) using the simplified reference tissue model and distribution volume ratios (DVRs) using Logan graphical analysis were calculated. Ratios obtained for a 10-min image, acquired between 30 and 40 min post-injection, were also calculated.
Cerebellum
activity was used as non-specific reference region.
Results:
In PD patients and as expected, striatal uptake was lower than in controls which is confirmed by BP
ND
, DVR, and ratios calculated for both striatal nuclei and SN, significantly inferior in PD patients compared with controls (
p
< 0.001).
Conclusions:
PET with [
18
F]LBT-999 could be an alternative to assess dopaminergic presynaptic injury in a clinical environment using a single 10 min acquisition.
...
PMID:Usefulness of PET With [
18
F]LBT-999 for the Evaluation of Presynaptic Dopaminergic Neuronal Loss in a Clinical Environment. 3297 45
