Dopamine Modulates Cell Cycle in the Lateral Ganglionic Eminence

“, and affects cell proliferation in the embryonic germinal zone”

“…circuits have formed fits with data from other parts of the developing CNS showing early expression of neurotransmitter receptors and suggesting that neurotransmitters may act on mitotic progenitor cells to regulate cell cycle or cell fate specification (Rueda et al. 2002; Ohtani et al. 2003).”

“It has furthermore been shown that dopamine and GABA interactions can influence these processes [187, 188].”

“A possible mechanism underlying the HFD-induced increase in neurogenesis may involve changes in the cell-cycle kinetics, as suggested for the dopamine system in the brain (Ohtani et al., 2003).”

“These findings are consistent with recent studies demonstrating that dopamine can regulate progenitor cell proliferation and neuronal migration during prenatal developmen”

“D2-like receptors are involved in promoting the proliferative effect of DA, whereas D1-like receptors decrease proliferation at the level of cell cycle entry (Diaz et al., 1997; Ohtani et al., 2003).”

“Dopamine is a catecholamine neurotransmitter that is implicated in ontogenesis and embryonic germinal zone proliferation during development, and modulates movement, mood and motivation in the adult brain [160–162].”

“Dopamine D2 ⁄ 3 agonist stimulates, whereas D1 agonist blocks, proliferation of embryonic striatal precursor cells (Ohtani et al., 2003).”

“Striatal projection MSNs originate in the VZ/SVZ of the LGE between E12 and P2 with a peak around E15, and subsequently migrate along guiding radial glia into the striatum (Marchand and Lajoie, 1986; Olsson et al., 1995, 1998).”

“In the lateral ganglionic eminence, for example, dopamine-mediated signaling influences proliferation of the dopamine receptor-expressing progenitor cells (Diaz et al., 1997; Ohtani et al., 2003).”

“A decrease in DAergic axons in deep layers of medial prefrontal cortex and decreased D1 receptor binding occurs in schizophrenic patients (Okubo et al., 1997; Akil et al., 1999).”

“In addition to serving a key neurotransmitter function, dopamine has been implicated in the regulation of endogenous neurogenesis during brain development (Borta and Hoglinger, 2007; Diaz et al., 1997; Ohtani et al., 2003) and adult neurogenesis in the SVZ by activating D2-like receptors on transit-amplifying progenit…”

“Of relevance, dopamine has been shown to modulate cell cycle kinetics in the embryonic lateral ganglionic eminence, such that dopamine D1 receptor activation reduces the entry of progenitor cells from the G1- to S-phase of the cell cycle, while D2 receptor activation promotes G1- to S-phase entry (43).”

“Consistent with this hypothesis, dopamine innervation of the forebrain striatal embryonic germinal zone (Ohtani et al., 2003) coincides temporally with the progressive extension of cell cycle time in embryonic NSCs (Martens et al.”

“In addition, we, and others have shown that dopaminergic receptor activation controls the proliferation of adult NPCs in vitro (9, 19, 20), suggesting that dopamine might interact with the EGFR in this neurogenic niche to promote proliferation.”

“Indeed, dopamine has been shown to either activate or inhibit, through D1- and D2-like receptors, respectively, the proliferation of precursor cells in the lateral ganglionic eminence, which is the neuroepithelial precursor of the neostriatum, and in the cortical neuroepithelium, the germinal precursor of the dorsomed…”

“…and dopamine modulation has been postulated to regulate baseline proliferation in an inhibitory manner (Kippin et al, 2005), although various studies suggest that the role of dopamine modulation in the regulation of neurogenesis might be more complex (Ohtani et al, 2003; Hoglinger et al, 2004).”

“D1 dopamine receptor activation decreases G1 to S cell cycle progression in embryonic progenitors (Ohtani et al., 2003).”

“Like the GABA receptors, migrating cortical interneurons also express D1 and D2, which are the receptors for dopamine [192,193].”

“One hypothesis is that dopamine receptors (D1) on the nestin-positive cells are involved in limiting the proliferative response (Ohtani et al., 2003); thus, DA denervation would release these cells from such inhibition.”

“Conversely, D2 agonists can increase neurogenesis in the adult mouse SVZ (Hoglinger et al., 2004) and in the explanted embryonic SVZ (Ohtani et al., 2003).”

“This view is supported by anatomical studies demonstrating that a dopaminergic innervation arrives during embryogenesis concomitantly in both the striatum and SVZ of the developing rodent brain (Ohtani et al., 2003; Popolo et al., 2004).”

“2004) might parallel those observed in the embryonic lateral ganglionic eminence in which proliferation is encouraged by D2-like receptors and inhibited by D1-like receptors (Ohtani et al. 2003; Popolo et al. 2004).”

“Furthermore, dopamine has been identified as a factor influencing neurogenesis in the developing nc. brain (Ohtani et al., 2003; Popolo et al., 2004) and adult brain (Höglinger et al., 2004; Yang et al., 2008).”

“A likely explanation for D1 receptor-like effects of dopamine is that the density of D1 receptor binding sites is 10-fold higher than D2 receptor binding sites in the E15 mouse striatum (Ohtani et al., 2003).”

“Dopamine is a neurotransmitter that can influence neurogenesis and tangential migration of cortical GABA neurons (Ohtani et al., 2003; Popolo et al., 2004; Crandall et al., 2007; McCarthy et al., 2007).”

“Tyrosine-hydroxylase positive axons enter the mouse basal forebrain by E13 and dorsal forebrain by E14, coincident with increases in dopamine content of these two regions [11,33,36].”

“Neurotransmitters and neurotransmitter receptors mediate and modulate excitatory and inhibitory signal transmission in the brain (Nguyen et al. 2001; Ohtani et al. 2003; Crandall et al. 2007).”

“. Furthermore, DA signaling at earlier developmental stages may contribute to postnatal neurogenesis and migration of inhibitory interneurons”

“Our previous data on LGE progenitors obtained from E13 mice suggested that the SVZ progenitors may be more responsive to D2-like receptor activation [Ohtani et al., 2003].”

“Based on our data, as well as recently reported data demonstrating that DRD2 signaling influences normal progenitor phenotype and differentiation (Ohtani et al., 2003; Baker et al., 2004; O’Keeffe et al., 2009; Winner et al., 2009), we next examined whether the observed self-renewal capacity of DRD2 cells was indeed D…”

“limit the entry from the G(1)- to the S-phase of the cell cycle in neuroepithelial precursor cells of the striatum, whereas the activation of D2-class receptors might have opposite effects (Ohtani et al., 2003).”

“A recent report indicates that dopamine, a neurotransmitter implicated in a variety of complex behaviours, modulates cell proliferation in the embryonic germinative zone of the lateral ganglionic eminence (Ohtani et al. 2003).”

“…receptor signaling pathways, prenatal drug exposure may adversely affect the developing brain by affecting the delicate process of neural proliferation (Ohtani et al., 2003), migration (Crandall et al., 2007), dendrite growth (Song et al., 2002), and axonal elongation (Wu et al., 2011).”

“Additionally, recent works show a developmental role for dopamine as regulator of precursor cell proliferation (Ohtani et al., 2003; Hoglinger et al., 2004).”

“However, dopamine has been shown to have a role in the development of neurons in the cerebral cortex such as GABA neurons (Crandall et al., 2007; Ohtani et al., 2003).”

“Agonists of both D2 and D3 receptors in mice have a powerful effect at upregulating proliferation in the SVZ (Diaz et al., 2000; Ohtani et al., 2003).”

“Studies in vitro indicated that dopamine D1-like receptor activation reduced the entry of progenitor cells from the G(1)- to the S-phase of the cell cycle [ 68 ], whereas D2-like activation inhibited neural stem cell proliferation [44].”

“DA is known to modulate neurogenesis in the embryonic brain (Ohtani et al., 2003; Popolo et al., 2004; McCarthy et al., 2007).”

“By acting on D1 receptors, ambient dopamine in the basal forebrain (Ohtani et al., 2003) promoted the migration of GABAergic interneurons into the cortex, while activation of D2 receptors has the opposite effect and impaired their migration from the MGEs and CGEs (Crandall et al., 2007; Fig.”

“…earliest neurochemical systems to develop in the embryo and can influence neurogenesis and neuronal and glial cell differentiation (Molliver, 1982; Lauder, 1988; Cases et al., 1995, 1996; Reinoso et al., 1996; Levitt et al., 1997; Bongarzone et al., 1998; Vitalis et al., 1998; Ohtani et al., 2003).”

“DA signaling also appears to be involved in prenatal neurogenesis itself within the neuroepithelial precursors of the striatum and cerebral cortex, via influences on cell cycle length [Ohtani et al., 2003; Zhang et al., 2005].”

“Defects in the DA system could lead to a disturbance in both brain maturation and the development of telencephalic cortical structures, as is observed in schizophrenics, because DA plays an important role in brain development (Lauder 1993; Ohtani et al. 2003).”

“The activation of the adenosine A2a receptor is antagonistic to the dopamine D2 receptor, which has been shown to enhance neurogenesis [25].”

“…of the present data with that obtained in rodents lacking dopaminergic substantia nigra neurons (pitx3−/− mice for example, Smidt et al., 2004), will allow understanding of the early role of endogenous dopamine on the development of the striatal network (Ohtani et al., 2003; Goffin et al., 2010).”

“…the growth of dendrites and axons have been suggested by a variety of pharmacological and genetic studies (Todd, 1992; Reinoso et al., 1996; Spencer et al., 1996; Behar et al., 1998, 1999, 2000; Lotto et al., 1999; Persico et al., 2000; Parish et al., 2001; Ohtani et al., 2003; Zhang et al., 2004).”

“…osmolality, protein kinase C activation, cytokines and steroid hormones have been shown to modulate AQP4 expression, it is not known whether DA influences the expression of AQP4 mRNA and protein, although an effect of DA on the water permeability of AQP4 has been described (Zelenina et al., 2002).”

“Dopamine modulates several specific features of prenatal and postnatal brain development, including effects on the regulation of neurogenesis (Ohtani et al., 2003), differentiation (Reinoso et al., 1996; Schmidt et al., 1996; Porter et al., 1999), and circuit formation (Tang et al., 2001).”

“late the cell cycle during neural development (Spencer et al., 1998; Ohtani et al., 2003), no direct evidence has”

“[141,142] Immunohistochemical and electron microscopy studies in the SVZ have shown that D2-like DAergic receptors are expressed predominately on C-cells (frequently dividing transit-amplifying cells), whereas A-cells (PSA-NCAMpositive-restricted neural precursors) express both D1- and D2-like receptors.”

“Moreover, modulation of dopamine signalling during development alters the proliferation of neural progenitor cells in the forebrain germinal zones (Zhang and Lidow , 2002 ; Ohtani et al. , 2003 ; Popolo et al. , 2004 ; McCarthy et al. , 2007 ).”

“This paradigm is similar to that seen with dopamine, as dopamine D1-like and D2-like receptor activation has been reported to produce mutually opposing effects on cell proliferation (Ohtani et al., 2003; Van Kampen et al., 2004).”

“Dopamine receptors D1 and D2 are expressed by cINs and have opposite effects on migration (Ohtani et al., 2003).”

“…2000; Anderson et al., 1999); 4—(Blue and Parnavelas, 1983; Parnavelas et al., 1977; Katz and Shatz, 1996); 5—(Graybiel and Hickey, 1982; Van Der Kooy and Fishell, 1986; Bayer, 1984; Sadikot and Sasseville, 1997); 6—(Ohtani et al., 2003); 7—(Sheth et al., 1998); 8—(Tepper et al., 1998).”

“The midbrain dopaminergic neurons and the striatum have been shown to have trophic effects on each other (Emgard-Mattson et al., 1997; Ohtani et al., 2003).”

“D2 receptor stimulation on cultured embryonic striatal cells facilitates progression through the cell cycle, whereas D1 decreases it (Ohtani et al., 2003).”

“Different components of DA signalling are expressed in progenitor cells in the CNS (Diaz et al., 1997; Ohtani et al., 2003).”

“Although DA has been shown to affect progenitor cell proliferation in the embryonic telencephalon (Ohtani et al., 2003; Zhang et al., 2005), our HPLC data showed that there were no differences in DA levels between WT and MAO AB KO mice at any developmental stage.”

“The neurotransmitter dopamine (DA), for example, modulates the cell cycle of lateral ganglionic eminence progenitors during development through DA D1- and D2-like receptors [13].”

“…variety of amino acid and monoamine transmitters including Á-aminobutyric acid (GABA), glutamate, dopamine and serotonin [Lo- Glutamate and Forebrain Proliferation Dev Neurosci 2004;26:218–228 219 Turco et al., 1995; Sadikot et al., 1998; Haydar et al., 2000; Luk et al., 2003; Ohtani et al., 2003].”

“of the striatum by TH+ fibers is already present at E14–E16 in the ventro-lateral part of the striatum (Ohtani et al., 2003) (Figure 1B).”

“Since, dopamine D1- and D2-receptors produce opposite effects on developmental events such as neurogenesis (Ohtani et al., 2003; Popolo et al., 2004) and neuronal migration (Crandall et al., 2007) and since dopamine’s overall effects on neurogenesis and neuronal migration in the embryonic striatum…”

“While activation of D1 promotes migration, D2 activation causes IN stop (Ohtani et al., 2003), indicating an opposite effect of these receptors in response to the same external cue.”

“Subtypes of ionotropic glutamate receptors and dopamine receptors also mediate heterogeneous proliferative responses in the ventricular or subventricular zones of the dorsal (Haydar et al. 2000) and ventral (Luk et al. 2003; Ohtani et al. 2003; Popolo et al. 2004) telencephalon.”

“Specifically, activation of dopamine D1 receptors causes an inhibition of G1-to-S phase transition of neural progenitor cells, whereas activation of D2 receptors causes the opposite effect (Ohtani et al., 2003).”