The colocalization of cholecystokinin and tyrosine hydroxylase mRNAs in mesencephalic dopaminergic neurons in the rat brain examined byin situ hybridization

Savasta, Marc; Ruberte, Esther; Palacios, J.M.; Mengod, Guadalupe

doi:10.1016/0306-4522(89)90063-8

Cited by 65 publications

(9 citation statements)

References 22 publications

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“…f~~~~~.~A obtained by unilateral lesion of these neurons by stereotaxic injection of 6-hydroxydopamine. The degeneration of the dopaminergic cells was followed by a loss of the hybridization signal with the dopamine receptor probe (data not shown) and also with an oligonucleotide complementary to the tyrosine hydroxylase mRNA (17). The presence of the dopamine D2 receptor mRNA in the substantia nigra pars compacta and ventral tegmental area is in good agreement with the presence of dopamine D2 receptor binding in these areas and with receptor losses following 6-hydroxydopamine lesion (3,16).…”

supporting

confidence: 69%

Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry.

Mengod¹,

Martinez-Mir²,

Vilaró³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

119

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ABSTRACT32P-labeled oligonucleotides derived from the coding region of rat dopamine D2 receptor cDNA were used as probes to localize cells in the rat brain that contain the mRNA coding for this receptor by using in situ hybridization histochemistry. The highest level of hybridization was found in the intermediate lobe of the pituitary gland. High mRNA content was observed in the anterior lobe of the pituitary gland, the nuclei caudate-putamen and accumbens, and the olfactory tubercle. Lower levels were seen in the substantia nigra pars compacta and the ventral tegmental area, as well as in the lateral mammillary body. In these areas the distribution was comparable to that of the dopamine D2 receptor binding sites as visualized by autoradiography using ligand. However, in some areas such as the olfactory bulb, neocortex, hippocampus, superior colliculus, and cerebellum, D2 receptors have been visualized but no significant hybridization signal could be detected. The mRNA coding for these receptors in these areas could be contained in cells outside those brain regions, be different from the one recognized by our probes, or be present at levels below the detection limits of our procedure. The possibility of visualizing and quantifying the mRNA coding for dopamine D2 receptor at the microscopic level will yield more information about the in vivo regulation of the synthesis of these receptors and their alteration following selective lesions or drug treatments.Two types of dopamine receptors mediate the effects of this neurotransmitter in the central nervous system and in the periphery, the so-called D1 and D2 receptor subtypes (1). Dopamine D2 receptors are the target for drugs used in the treatment of schizophrenia and Parkinson disease and for regulation of prolactin secretion (2). Their distribution in the mammalian brain, including human, has been extensively examined by using receptor binding autoradiography (3). Dopamine D2 receptors have been directly visualized in living humans by positron-emission tomography (PET) (4). Binding and PET studies have suggested that dopamine D2 receptor levels may be elevated in schizophrenics (refs. 5, 6; see, however, ref. 7). Although dopamine receptors can be visualized at the light microscopic level by means of receptor binding autoradiography, the cellular localization of these receptors cannot be determined with this technique. The use of neurotoxin or mechanical brain lesions combined with binding studies has resulted in contradictory results (8-10). In order to establish the exact cellular localization of dopamine receptors, tools with higher anatomical resolution are necessary. The cloning and sequencing of the gene coding for the rat dopamine D2 receptor has been reported recently (11), thus opening the way to the development of these tools. On the basis of this sequence we have synthesized oligonucleotide probes and used them to visualize the regional distribution of the cells containing mRNA coding for the dopamine D2 receptor in the rat brain and pituitary gland b...

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supporting

confidence: 69%

Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry.

Mengod¹,

Martinez-Mir²,

Vilaró³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

119

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“…In the striatum, most of the gene expression changes were an increase, whereas in the substantia nigra a number of genes increased in expression (value in red) and a number of genes decreased in expression (value in green). Those pathways identified by the genes with an increase in expression are shown in red, whereas those identified by genes that decrease in expression are shown in green down-regulated reveals several genes associated with DA neurons, these include the D2 DA receptor, tyrosine hydroxylase, VMAT, kappa opioid receptor [11], GIRK2 (mutated in the weaver mouse) [12] and CCK [13,14].…”

Section: Gene Sets In the Striatummentioning

confidence: 97%

Molecular Profiling of a 6-Hydroxydopamine Model of Parkinson’s Disease

DiLella

Lis

et al. 2010

Neurochem Res

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Convection enhanced delivery of 6-hydroxydopamine (6-OHDA) to the rat striatum results in a model of Parkinson's disease. An important feature of this unilateral model is the progressive loss of dopaminergic (DA) neurons over the course of several weeks. To improve the understanding of this model, gene expression changes in the substantia nigra, which contains the DA neuron cell bodies, and the striatum, which contains the DA neuron synaptic terminals, were examined using DNA microarrays. Samples were collected and behavior was analyzed from vehicle and toxin treated animals at 3 days, 1 week, 2 weeks and 4 weeks following 6-OHDA treatment. Tissue DA content was determined and samples from animals which exhibited a substantial depletion of striatal DA were included in the subsequent gene expression analysis. The results of the gene expression analysis indicated that 6-OHDA elicits a vigorous inflammatory response, comprised of several distinct pathways, in the striatum at the earliest time point tested. In contrast, relatively few gene expression changes were observed in the SN at the 3-day time point. In both tissues examined there was evidence for a vigorous inflammatory response at the 1- and 2-week time points, which was substantially diminished by the 4-week time point. Inflammation plays a prominent role in the 6-OHDA model of Parkinson's disease.

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“…Surviving TH+ cells were found usually in ventromedial aspects of the anterior SNc and exceptionally in the SNr of s3 and hl. Savasta et al 15) have reported complete disappearance of TH oligonucleotide labeling after treatment with 6-OHDA, but 15% of SN neurons with catecholamine fluorescence survive nigral application of a smaller dose (4.8 µg) of 6-OHDA.7) This discrepancy may result from differences in the injection site, the dose of 6-OHDA, or detection sensitivity.…”

Section: Introductionmentioning

confidence: 99%

6-Hydroxydopamine Lesion Prevents Induction of Tyrosine Hydroxylase by Haloperidol in the Rat Substantia Nigra, Pars Reticulata.

Stork

Kumazaki

Nishino

et al. 1994

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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We investigated the number of tyrosine hydroxylase (TH)-positive neurons in the rat substantia nigra (SN) after unilateral lesion of SN dopamine neurons with intranigral 6-hydroxydopamine (6-OHDA) injection. Non-radioactive in situ hybridization procedure and immunohistochemistry detected much less (<5%) TH-positive neurons in the lesioned SN, compared with the contralateral side. Single administration of a dopamine antagonist haloperidol failed to increase TH labeling on the lesioned side, although it increased that in the contralateral SN pars reticulata (SNr), as in the case of unlesioned animals. These results indicate that 6-OHDA destroyed not only TH-positive SN neurons but also TH-negative but -inducible SNr neurons. It is probable that these "TH inducible" SNr neurons are dopaminergic neurons although they usually do not express TH at detectable levels.

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The colocalization of cholecystokinin and tyrosine hydroxylase mRNAs in mesencephalic dopaminergic neurons in the rat brain examined byin situ hybridization

Cited by 65 publications

References 22 publications

Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry.

Localization of the mRNA for the dopamine D2 receptor in the rat brain by in situ hybridization histochemistry.

Molecular Profiling of a 6-Hydroxydopamine Model of Parkinson’s Disease

6-Hydroxydopamine Lesion Prevents Induction of Tyrosine Hydroxylase by Haloperidol in the Rat Substantia Nigra, Pars Reticulata.

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