A possible role for dopamine D3 receptor stimulation in the induction of neurogenesis in the adult rat substantia nigra

Kampen, Jackalina M. Van; Robertson, Harold A.

doi:10.1016/j.neuroscience.2005.07.054

Cited by 96 publications

(73 citation statements)

References 25 publications

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“…D5R mRNA was significantly higher in this region compared to the embryonic proliferative domains. Once again, expression of dopamine receptor mRNAs is consistent with the reported effects of dopamine receptor agonists and antagonists on cell proliferation in the subventricular zone [15,20,53,54]. Each brain region showed unique characteristics with respect to developmental regulation of the five mRNAs.…”

Section: Discussionsupporting

confidence: 84%

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: 84%

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

2007

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“…2), consistent with the published anatomical data [4,9]. The next highest TH band in the fetal brain was detected in GE, consistent with the presence of DA neurons in the gangliothalamic body [49,51,55].…”

Section: Da Receptor Proteins In Hescs Undergoing Differentiationsupporting

confidence: 88%

“…1B). This finding is consistent with reports that in adult rats, a 10-fold increase of proliferating cells in the neostriatum has been observed upon stimulation with a D3 agonist [52,55].…”

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confidence: 93%

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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“…Their results suggested that dopamine neurons are constantly turned over, although they die and are replaced at a low rate. Since then, a series of publications (e.g., Van Kampen et al, 2005 ) has confirmed the potency of dopamine as a stimulator of precursor cell proliferation in the rodent SVZ. Even more convincing, research by Freundlieb et al (2006) in aged primates has demonstrated a subventricular dopaminergic projection system from the substantia nigra pars compacta to the SVZ that suggests the possibility of using endogenous neural precursor cells to treat aged primates like ourselves.…”

Section: Location Locationmentioning

confidence: 99%

Can endocrine disruptors influence neuroplasticity in the aging brain?

Weiss

2007

NeuroToxicology

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Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer's disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, antiandrogens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle.

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A possible role for dopamine D3 receptor stimulation in the induction of neurogenesis in the adult rat substantia nigra

Cited by 96 publications

References 25 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

Dopamine Receptors in Human Embryonic Stem Cell Neurodifferentiation

Can endocrine disruptors influence neuroplasticity in the aging brain?

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