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  • 1
    ISSN: 0309-1651
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Changes in striatal dopamine D2 receptor mRNA levels provoked by unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine pathway were studied by in situ hybridization. The influence of embryonic dopaminergic neurons implanted into the dopamine-depleted striatum on the lesion-induced changes was also examined. Changes in D2 mRNA levels were compared with changes in D2 receptor densities measured in the same animals by receptor autoradiography using [3H]spiperone or [3H]SDZ 205–501 as ligands. The distribution of D2 mRNA in the striatum of control animals closely paralleled that of the D2 receptor itself, as assessed by autoradiography, and the highest density of D2 mRNA occurred in the lateral part of the striatum. One month after lesion, levels of D2 mRNA were 34% higher in the dorsolateral part of the dopamine-depleted striatum than in the corresponding region of the contralateral control striatum. D2 receptor density in this region was increased by 40% relative to the control level. No significant increases could be measured in the medial part of the striatum. The increases in the lateral part were similar at 7 months post-lesion; however, at this time the increase in both D2 mRNA and receptor levels had spread to the medial part of the striatum as well. In the graft-bearing striatum levels of both D2 mRNA and D2 receptors reverted to control levels. This study shows that the post-lesion increase in striatal dopamine receptor and mRNA level is a biphasic phenomenon with a late-occurring component in the medial striatum. It also shows that once the increase in striatal D2 receptor gene expression is accomplished, it is maintained unchanged for long periods, similar to that of D2 receptor levels themselves. Moreover, grafts of embryonic dopaminergic neurons are able to modulate the expression of the dopamine D2 receptor gene.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Stereotaxic injection of a limited amount of 6- hydroxydopamine in the lateral part of the rat substantia nigra induces a partial degeneration of the nigrostriatal dopaminergic system. This animal model in which the destruction of the dopaminergic nigral cell population reaches -50% could be considered as a preclinical Parkinson's model. Autoradiography of dopaminergic uptake sites performed with a specific marker ([3H]GBR 12935) allowed the precise determination of dopaminergic denervated and non-denervated areas in the striatum 1 month after partial lesion of the substantia nigra pars compacta. In both striatal areas, dopaminergic D1 and D2receptor densities and dopaminergic D2 and preproenkephalin mRNAs levels were measured by autoradiography and in situ hybridization coupled to an image analysis system. Our results show that in the denervated striatal subregion, none of the dopaminergic targets were modified, contrary to the observations made after complete lesion of the nigrostriatal DA system at the same post-lesion delay. However, striatal Fos activation induced by amphetamine (5 mg/kg i.p., 2 h before killing) revealed that the number of Fos-positive cells detected in the denervated striatal subregion was lower than that observed in the non-denervated one. These data argue in favour of the existence of compensatory mechanisms different from the up-regulation of DA receptor densities, thereby allowing the maintenance of striatal dopaminergic transmission. Such mechanisms could contribute to the delay of the appearance of neurological symptoms (which are reported to be clinically apparent only when depletion of striatal dopamine levels reaches near 80%) in Parkinsonian patients.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1463
    Keywords: Dopamine uptake sites ; autoradiography ; immunohistochemistry ; image analysis ; regional distribution ; [3H]GBR 12935 ; rat brain ; dopaminergic system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The regional distribution of dopamine (DA) uptake sites in the rat brain has been studied by quantitative autoradiography using [3H]GBR 12935 as a ligand. The binding of [3H]GBR 12935 to striatal sections was saturable and of high affinity (Kd = 1.6 nM); it occurred at a single population of sites and possessed the pharmacological features of the DA uptake sites. The highest densities of [3H]GBR 12935 binding sites were found in the caudate-putamen, nucleus accumbens, olfactory tubercle, ventral tegmental area and substantia nigra (especially in the pars compacta). Moderate levels of [3H]GBR 12935 binding were observed in globus pallidus, thalamus, hypothalamus, hippocampus, amygdala (basolateral nucleus) and prefrontal and cingular cortices. This regional distribution of [3H]GBR 12935 binding closely correlated with the reported distribution of dopaminergic nerve terminals. The topographical distribution of [3H]GBR 12935 has also been studied in detail in striatal subregions and this distribution was compared, using quantitative TH immunoreactivity, to the density of striatal dopaminergic nerve terminals. There is good overlapping between these two regional distributions, the highest density of both markers was found in the lateral part of the striatum and a similar rostro-caudal gradient has been observed. A dopaminergic denervation caused a complete loss of [3H]GBR 12935 in basal ganglia ipsilateral to the lesion.
    Type of Medium: Electronic Resource
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