Activation of dopaminergic D1 receptors promotes morphogenesis of developing striatal neurons

Schmidt, Ulrike; Beyer, Cordian; Oestreicher, A.B.; Reisert, Ingrid; Schilling, Karl; Pilgrim, Christoph

doi:10.1016/0306-4522(96)00201-1

Cited by 93 publications

(87 citation statements)

References 39 publications

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“…1). Ascorbic acid was used to retard oxidation of L-DOPA in the water [32,44,50]. The treatments began on the 11 th day of pregnancy and lasted until parturition.…”

Section: Resultsmentioning

confidence: 99%

“…Activation of dopamine receptors influences cell proliferation in the lateral ganglionic eminence (LGE) and the neuroepithelium of the frontal cortex in embryonic mice [39,43,72,73] and in the subventricular zone and hippocampal dentate gyrus in the adult mice [18,22,64]. Dopamine receptor activation also influences GABA neuron migration from the basal forebrain to the cerebral cortex [13] and differentiation of cortical and striatal neurons [50,56].…”

Section: Introductionmentioning

confidence: 99%

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Elevated dopamine levels during gestation produce region-specific decreases in neurogenesis and subtle deficits in neuronal numbers

2007

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Dopamine levels in the fetal brain were increased by administering the dopamine precursor 3,4-dihydroxy-L-phenylalanine (L-DOPA) to pregnant mice in drinking water. The L-DOPA exposure decreased bromodeoxyuridine (BrdU) labeling in the lateral ganglionic eminence and frontal cortical neuroepithelium but not medial or caudal ganglionic eminences. The regional differences appear to reflect heterogeneity in precursor cells' responses to dopamine receptor activation. Relative numbers of E15 generated neurons were decreased at postnatal day 21 (P21) in the caudate-putamen, nucleus accumbens and frontal cortex but not globus pallidus in the L-DOPA group. TUNEL labeling did not show significant differences on P0, P7 or P14 in the caudate-putamen or frontal cortex, suggesting that cell death was not altered. Although virtually all cells in the P21 brains that were labeled with the E15 BrdU injection were NeuN-positive, stereological analyses showed no significant changes in total numbers of NeuN-positive or NeuN-negative cells in the P21 caudate-putamen or frontal cortex. Thus persisting deficits in neuronal numbers were evident in the L-DOPA group only by birth-dating analyses and not upon gross histological examination of brain sections or analysis of total numbers of neurons or glia. One explanation for this apparent discrepancy is that L-DOPA exposure decreased cell proliferation at E15 but not at E13. By E15, expansion of the neuroepithelial precursor pool is complete and any decrease in cell proliferation likely produces only marginal decreases in the total numbers of cells generated. Our L-DOPA exposure model may be pertinent to investigations of neurological dysfunction produced by developmental dopamine imbalance.

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“…1). Ascorbic acid was used to retard oxidation of L-DOPA in the water [32,44,50]. The treatments began on the 11 th day of pregnancy and lasted until parturition.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated dopamine levels during gestation produce region-specific decreases in neurogenesis and subtle deficits in neuronal numbers

2007

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“…Rational for adding DA to the hESC neurodifferentiation protocol DA has been found to regulate neuronal proliferation and differentiation via DA receptors [64,65]. More importantly, DA receptors have been theorized to play a critical role in the development of midbrain dopaminergic neurons [33,66] tempting us to speculate that DA may be able to boost the production of dopaminergic neurons from hESCs.…”

Section: Da Receptor Signaling In Hesc Coloniesmentioning

confidence: 99%

“…Second, the 5 well-established DA receptor subtypes and the products of their heterodimerizations [32] point to a plethora of intracellular pathways that can potentially be manipulated by conditioning the culture media. For example, both D1-like [65] and D-2 like receptors [66] affect neuronal development. Also, dopaminergic signals can be manipulated by turning them ON or OFF.…”

Section: Da Receptor Signaling In Hesc Coloniesmentioning

confidence: 99%

Dopamine Receptors in Human Embryonic Stem Cell Neurodifferentiation

Belinsky

Sirois

Rich

et al. 2013

Stem Cells and Development

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We tested whether dopaminergic drugs can improve the protocol for in vitro differentiation of H9 human embryonic stem cells (hESCs) into dopaminergic neurons. The expression of 5 dopamine (DA) receptor subtypes (mRNA and protein) was analyzed at each protocol stage (1, undifferentiated hESCs; 2, embryoid bodies [EBs]; 3, neuroepithelial rosettes; 4, expanding neuroepithelium; and 5, differentiating neurons) and compared to human fetal brain (gestational week 17-19). D2-like DA receptors (D2, D3, and D4) predominate over the D1-like receptors (D1 and D5) during derivation of neurons from hESCs. D1 was the receptor subtype with the lowest representation in each protocol stage (Stages 1-5). D1/D5-agonist SKF38393 and D2/D3/D4-agonist quinpirole (either alone or combined) evoked Ca 2 + responses, indicating functional receptors in hESCs. To identify when receptor activation causes a striking effect on hESC neurodifferentiation, and what ligands and endpoints are most interesting, we varied the timing, duration, and drug in the culture media. Dopaminergic agonists or antagonists were administered either early (Stages 1-3) or late (Stages 4-5). Early DA exposure resulted in more neuroepithelial colonies, more neuronal clusters, and more TH + clusters. The D1/D5 antagonist SKF83566 had a strong effect on EB morphology and the expression of midbrain markers. Late exposure to DA resulted in a modest increase in TH + neuron clusters (*75%). The increase caused by DA did not occur in the presence of dibutyryl cAMP (dbcAMP), suggesting that DA acts through the cAMP pathway. However, a D2-antagonist (L741) decreased TH + cluster counts. Electrophysiological parameters of the postmitotic neurons were not significantly affected by late DA treatment (Stages 4-5). The mRNA of mature neurons (VGLUT1 and GAD1) and the midbrain markers (GIRK2, LMX1A, and MSX1) were lower in hESCs treated by DA or a D2-antagonist. When hESCs were neurodifferentiated on PA6 stromal cells, DA also increased expression of tyrosine hydroxylase. Although these results are consistent with DA's role in potentiating DA neurodifferentiation, dopaminergic treatments are generally less efficient than dbcAMP alone.

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“…Several studies have shown that DA and stimulation of DA receptors facilitate neuronal growth [18][19][20] . However, these studies used striatal neurons; so, such molecular mechanisms of DA-dependent facilitation of neuronal growth may not necessarily be applicable to PFC neurons.…”

mentioning

confidence: 99%

Prefrontal cortical dopamine from an evolutionary perspective

Lee

Goto

2015

Neurosci. Bull.

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In this article, we propose the hypothesis that the prefrontal cortex (PFC) acquired neotenic development as a consequence of mesocortical dopamine (DA) innervation, which in turn drove evolution of the PFC into becoming a complex functional system. Accordingly, from the evolutionary perspective, decreased DA signaling in the PFC associated with such adverse conditions as chronic stress may be considered as an environmental adaptation strategy. Psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder may also be understood as environmental adaptation or a by-product of such a process that has emerged through evolution in humans. To investigate the evolutionary perspective of DA signaling in the PFC, domestic animals such as dogs may be a useful model.

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Activation of dopaminergic D1 receptors promotes morphogenesis of developing striatal neurons

Cited by 93 publications

References 39 publications

Elevated dopamine levels during gestation produce region-specific decreases in neurogenesis and subtle deficits in neuronal numbers

Elevated dopamine levels during gestation produce region-specific decreases in neurogenesis and subtle deficits in neuronal numbers

Dopamine Receptors in Human Embryonic Stem Cell Neurodifferentiation

Prefrontal cortical dopamine from an evolutionary perspective

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