Ontogeny of D1a and D2 dopamine receptor subtypes in rat brain using in situ hybridization and receptor binding

Schambra, Uta B.; Duncan, Gary E.; Breese, George R.; Fornaretto, M. G.; Caron, Marc G.; Fremeau, Robert T.

doi:10.1016/0306-4522(94)90315-8

Cited by 196 publications

(136 citation statements)

References 75 publications

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“…D1-like and D2-like receptor binding sites appear in the mouse basal forebrain by E13 [34], at least a day after the appearance of the mRNA. Similar findings were reported earlier by others [42]. It is possible that developmental regulation of mRNA and binding site expression occurs by independent mechanisms.…”

Section: Discussionsupporting

confidence: 91%

“…Similar correlations do not exist between mRNA and receptor binding site expression for D1 or D2 family of receptors during development or at maturity [17,38,42]. Previous reports show that D1-like binding sites predominate over D2-like binding sites in the embryonic and postnatal striatum [17,38,42]. This is in contrast to the higher D2-like mRNA expression in the striatum during pre-and postnatal development reported in this study (Fig.…”

Section: Discussionsupporting

confidence: 71%

“…Therefore, we suggest that mRNA expression is a reliable marker of receptor protein expression in the developing and mature brain. Similar correlations do not exist between mRNA and receptor binding site expression for D1 or D2 family of receptors during development or at maturity [17,38,42]. Previous reports show that D1-like binding sites predominate over D2-like binding sites in the embryonic and postnatal striatum [17,38,42].…”

Section: Discussionmentioning

confidence: 63%

“…The ontogeny of dopamine receptors has been examined previously by using receptor binding, in situ RNA hybridization or RT-PCR in the brains of rodents and primates [13,14,17,26,38,41,42,45,46]. With the exception of the in situ hybridization studies, the mRNA expression was not analyzed in anatomically defined regions of the embryonic and postnatal brain.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that developmental regulation of mRNA and binding site expression occurs by independent mechanisms. Perhaps receptor binding site expression occurs upon exposure to dopamine, the endogenous ligand, and mRNA expression occurs earlier, independent of exposure to dopamine [42].…”

Section: Discussionmentioning

confidence: 99%

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Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

2007

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The outcome of dopaminergic signaling and effectiveness of dopaminergic drugs depend on the relative preponderance of each of the five dopamine receptors in a given brain region. The separate contribution of each receptor to overall dopaminergic tone is difficult to establish at a functional level due to lack of receptor subtype specific pharmacological agents. A surrogate for receptor function is receptor protein or mRNA expression. We examined dopamine receptor mRNA expression by quantitative reverse transcription real-time PCR in the striatum, globus pallidus, frontal cortex and cingulate cortex of embryonic and postnatal mice. Samples of each region were collected by laser capture microdissection. D1-and D2-receptor mRNAs were the most abundant in all the regions of the mature brain. The D1-receptor was predominant over the D2-receptor in the frontal and cingulate cortices whereas the situation was reversed in the striatum and globus pallidus. In the proliferative domains of the embryonic forebrain, D3-, D4-and D5-receptors were predominant. In the corpus striatum and cerebral cortex, the D3-and D4-receptors were the only receptors that showed marked developmental regulation. By analyzing D1 receptor protein expression, we show that developmental changes in mRNA expression reliably translate into changes in protein levels, at least for the D1-receptor.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

2007

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Ontogeny of the striatal neurons expressing the D1 dopamine receptor in humans

et al. 1996

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We studied D1 dopamine receptor (D1R) gene expression in the human striatum during ontogeny by in situ hybridization, immunohistochemistry, and D1R ligand autoradiography. D1R mRNA, protein, and binding sites ([3H]SCH 23390) were detected in the striatum from week 12 of fetal life. At this time, D1R mRNA was predominant in the striosomal neurons; D1R immunoreactivity (D1R-IR) and D1R binding sites displayed a pattern similar to D1R mRNA. D1R-IR was essentially present in striosomal cell bodies and neuropil, whereas only a few cell bodies were detected in the matrix. From week 20 of fetal life, D1R gene expression developed in the matrix neurons as well, thus leading to an even D1R mRNA expression throughout striosomes and matrix compartments at birth. Comparative analysis of the expression of D1R and dynorphin mRNA show the same developmental patchy pattern up to week 26. Indeed, neurons expressing the D1R gene contain dynorphin mRNA; in contrast, they do not express the preproenkephalin A gene. At birth, the pattern of D1R mRNA expression level was sharply different from that of dynorphin (DYN) gene expression. High DYN mRNA expression was restricted to the striosomes, whereas high D1R mRNA expression was present in the whole striatum. These results demonstrate that, during human ontogeny, functional D1 receptors are expressed as early as week 12 in the striatum, developing initially in the striosomal neurons containing high dynorphin mRNA content. Toward the end of fetal life, there is a dissociation between D1R and DYN expression levels, suggesting that neuroanatomical or neurochemical modifications occur at this period, which may contribute to the regulation of the tone of the striatal D1R and DYN gene with topological specificity.

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Molecular anatomy of the development of the human substantia nigra

et al. 1997

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A series of 15 fetal and perinatal human brains (from week 12 of fetal life to day 2 after birth) was studied in order to describe the anatomical and molecular correlates of the substantia nigra ontogeny. In situ hybridization, immunohistochemistry and binding studies were used to detect D2 dopamine receptor (D2R) mRNA, D2R binding sites, dopamine membrane transporter (DAT) mRNA, tyrosine hydroxylase (TH) protein D1 dopamine receptor (D1R) protein and D1R binding sites. Dopaminergic (DA) neurons of the substantia nigra were detected through TH immunoreactivity from week 12. At week 16, the substantia nigra was clearly delineated as a compact group of intermingled neurons and fibers. From week 19, groups of DA neurons were segregated from the pars reticulata. These groups have been divided into the substantia nigra pars compacta, the ventral tegmental area and the retrorubral area. The DA neurons exhibited a gradual increase in size and branching development until birth. From week 12 onward they expressed several other markers of dopamine transmission, i.e., D2R mRNA, D2R binding sites and DAT mRNA. The ventral tegmental area expressed lower levels of mRNA for DAT and D2R than the pars compacta. From week 12, D1R immunoreactivity and D1R binding sites were also present in the substantia nigra pars reticulata. This suggests that projecting striatonigral neurons, known to express the D1R gene, have developed pathways connecting with the substantia nigra by week 12. Our results demonstrate that the developing substantia nigra in human displays early transcriptional and translational activity for the main constituents of dopaminergic transmission from week 12 and receives at this time dopaminoceptive inputs bearing D1 receptors from the striatum.

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Ontogeny of D1a and D2 dopamine receptor subtypes in rat brain using in situ hybridization and receptor binding

Cited by 196 publications

References 75 publications

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Dopamine receptor mRNA and protein expression in the mouse corpus striatum and cerebral cortex during pre- and postnatal development

Ontogeny of the striatal neurons expressing the D1 dopamine receptor in humans

Molecular anatomy of the development of the human substantia nigra

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