The PACAP Ligand/Receptor System Regulates Cerebral Cortical Neurogenesis<sup>a</sup>

DiCicco‐Bloom, Emanuel; Lu, Nairu; Pintar, John E.; Zhang, Jiwen

doi:10.1111/j.1749-6632.1998.tb11188.x

Cited by 59 publications

(33 citation statements)

References 53 publications

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“…From this point of view, it should be noted that PACAP significantly increases both MTT reduction and neurosphere size. This polypeptide was shown to regulate the proliferation and differentiation in neural progenitor cells during embryonic development (63). In our hands, mRNA expression was not detected for any isoforms of adrenergic β-receptors known to be positively coupled to adenylyl cyclase in undifferentiated neural progenitor cells.…”

Section: A Role Of Group III Mglur In Neurogenesismentioning

confidence: 68%

Neurogenesis Mediated by γ-Aminobutyric Acid and Glutamate Signaling

2009

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Abstract. In this review, we will summarize our ongoing studies on the functionality of both γ-aminobutyric acid (GABA) and glutamate receptors expressed by undifferentiated neural progenitor cells isolated from embryonic rodent brains. Cells were cultured with growth factors for the formation of round spheres by clustered cells under floating conditions, whereas a reverse transcription polymerase chain reaction analysis revealed expression of mRNA for particular subtypes of different ionotropic and metabotropic GABA and glutamate receptors in undifferentiated progenitors and neurospheres. Moreover, sustained exposure to either GABAergic or glutamatergic agonists not only modulated the size of neurospheres formed, but also affected spontaneous and induced differentiation of neural progenitor cells into particular progeny cell lineages such as neurons and astroglia. Both GABA and glutamate could play a pivotal role in the mechanisms underlying proliferation for self-replication along with the determination of subsequent differentiation fate toward particular progeny lineages through activation of their receptor subtypes functionally expressed by undifferentiated neural progenitor cells. Accordingly, neurogenesis seems to be also under control by GABAergic and glutamatergic signaling in developing brains as seen with neurotransmission in adult brains.

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Section: A Role Of Group III Mglur In Neurogenesismentioning

confidence: 68%

Neurogenesis Mediated by γ-Aminobutyric Acid and Glutamate Signaling

2009

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“…These include widely expressed growth factors [bFGF, EGF, IGF, TGF-␤, and pituitary adenylate cyclase-activating polypeptide (PACAP)], neurotrophic factors (NT3, NT4, BDNF, and NGF), and neurotransmitters (GABA, glutamate, VIP, and monoamines). Factors that have been reported to promote neuroblast proliferation include NGF (Cattaneo and McKay, 1990), bFGF (Ghosh and Greenberg, 1995;Cavanagh et al, 1997), EGF (Burrows et al, 1997), IGF (Nielsen and Gammeltoft, 1990;Ye et al, 1996), and VIP (Gressens et al, 1998), whereas 5-hydroxytryptamine (5-HT) (Lavdas et al, 1997), norepinephrine (Ghiani et al, 1999), glutamate and GABA (LoTurco et al, 1995), and PACAP (Lu and DiCicco-Bloom, 1997;DiCicco-Bloom et al, 1998) have been shown to inhibit proliferation and/or to elicit cell-cycle withdrawal.…”

Section: Candidate Molecule For the Mitogenic Effectmentioning

confidence: 99%

“…Glutamate and GABA influence DNA synthesis of cortical precursors in the rat ventricular and subventricular zones (LoTurco et al, 1995, Haydar et al, 2000. There is evidence suggesting that the cortical plate exerts an inhibitory feedback influence on proliferation in the ventricular zone (DiCicco-Bloom et al, 1998;Polleux et al, 1998) that could be relayed by descending corticofugal axons (Kim et al, 1991;Miller et al, 1993;McConnell et al, 1994;Meyer et al, 1998).…”

Section: Afferent Control Of Morphogenesis In the Cnsmentioning

confidence: 99%

Cell-Cycle Kinetics of Neocortical Precursors Are Influenced by Embryonic Thalamic Axons

et al. 2001

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Thalamic afferents are known to exert a control over the differentiation of cortical areas at late stages of development. Here, we show that thalamic afferents also influence early stages of corticogenesis at the level of the ventricular zone. Using an in vitro approach, we show that embryonic day 14 mouse thalamic axons release a diffusable factor that promotes the proliferation of cortical precursors over a restricted developmental window. The thalamic mitogenic effect on cortical precursors (1) shortens the total cell-cycle duration via a reduction of the G 1 phase; (2) facilitates the G 1 /S transition leading to an increase in proliferative divisions; (3) is significantly reduced by antibodies directed against bFGF; and (4) influences the proliferation of both glial and neuronal precursors and does not preclude the action of signals that induce differentiation in these two lineages. We have related these in vitro findings to the in vivo condition: the organotypic culture of cortical explants in which anatomical thalamocortical innervation is preserved shows significantly increased proliferation rates compared with cortical explants devoid of subcortical afferents. These results are in line with a number of studies at subcortical levels showing the control of neurogenesis via afferent fibers in both vertebrates and invertebrates. Specifically, they indicate the mechanisms whereby embryonic thalamic afferents contribute to the known early regionalization of the ventricular zone, which plays a major role in the specification of neocortical areas. Key words: development; cortex; proliferation; areal specification; mouse; ventricular zoneCells of the cerebral cortex originate from the ventricular and subventricular zones of the embryonic telencephalon. The heterogeneous population of precursors lining the ventricular zone divide, migrate, and differentiate to form the cerebral cortex. Although many of the developmental events occurring during corticogenesis have been described (Angevine and Sidman, 1961;Smart, 1973;Smart and Smart, 1982;Rakic, 1988;Bayer and Altman, 1991), the contribution of early mechanisms that determine the phenotypes of cortical neurons and specify the identity of cortical areas still has to be resolved (McConnell, 1995).The sensory periphery exerts an important control over the development of the immature cortical plate via thalamic afferents (O'Leary, 1989). Such afferent specification of cortex (Killackey, 1990) is in line with in vivo and in vitro experiments showing that thalamic afferents influence cell survival and differentiation (Repka and Cunningham, 1987;Windrem and Finlay, 1991;Lotto and Price, 1996;Price and Lotto, 1996;Zhou et al., 1999). However, there is also clear evidence that there is a specification of cortical neuron phenotype at the level of the ventricular zone before migration to the cortical plate (Arimatsu et al., 1992;Cohen-Tannoudji et al., 1994;Soriano et al., 1995;Levitt et al., 1997;Miyashita-Lin et al., 1999, Nakagawa et al., 1999.Given the developmental impa...

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“…It is widely distributed in neurons of the brain and peripheral nervous system [2], and has multiple transmitter and trophic functions [3]. PACAP affects neuronal cell cycle exit during central nervous system formation [4], promotes neuronal differentiation in cultured rat sympathetic neuroblasts [5,6], differentially modulates proliferation of central and peripheral neuroblasts [7], stimulates neuritogenesis in PC12 cells [8,9] and regulates neuron-specific gene expression in human neuroblastoma cell lines [10]. PACAP prevents apoptotic cell death and protects cultured rat cortical neurons against glutamate-induced cytotoxicity [11], and dopaminergic neurons against 6-hydroxydopamine-induced cytotoxicity [12].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by endogenous and exogenous PACAP following stroke

Chen¹,

Samal²,

Hamelink³

et al. 2006

Regulatory Peptides

105

113

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We investigated the effects of PACAP treatment, and endogenous PACAP deficiency, on infarct volume, neurological function, and the cerebrocortical transcriptional response in a mouse model of stroke, middle cerebral artery occlusion (MCAO). PACAP-38 administered i.v. or i.c. v. 1 h after MCAO significantly reduced infarct volume, and ameliorated functional motor deficits measured 24 h later in wild-type mice. Infarct volumes and neurological deficits (walking faults) were both greater in PACAP-deficient than in wild-type mice, but treatment with PACAP reduced lesion volume and neurological deficits in PACAP-deficient mice to the same level of improvement as in wild-type mice.A 35,546-clone mouse cDNA microarray was used to investigate cortical transcriptional changes associated with cerebral ischemia in wild-type and PACAP-deficient mice, and with PACAP treatment after MCAO in wild-type mice. 229 known (named) transcripts were increased (228) or decreased (1) in abundance at least 50% following cerebral ischemia in wild-type mice. 49 transcripts were significantly up-regulated only at 1 h post-MCAO (acute response transcripts), 142 were up-regulated only at 24 h post-MCAO (delayed response transcripts) and 37 transcripts were up-regulated at both times (sustained response transcripts). More than half of these are transcripts not previously reported to be altered in ischemia.A larger percentage of genes up-regulated at 24 hr than at 1 hr required endogenous PACAP, suggesting a more prominent role for PACAP in later response to injury than in the initial response. This is consistent with a neuroprotective role for PACAP in late response to injury, i.e., even when administered 1 hr or more after MCAO. Putative injury effector transcripts regulated by PACAP include β-actin, midline 2, and metallothionein 1. Potential neuroprotective transcripts include several demonstrated to be PACAP-regulated in other contexts. Prominent among these ☆ Data deposition: The raw data from the expression profiling experiments reported in this paper have been deposited in the Gene Expression Omnibus database (accession no. GSE5902). The GSE5902 will be hyperlinked when it is released. were transcripts encoding the PACAP-regulated gene Ier3, and the neuropeptides enkephalin, substance P (tachykinin 1), and neurotensin.

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The PACAP Ligand/Receptor System Regulates Cerebral Cortical Neurogenesis^a

Cited by 59 publications

References 53 publications

Neurogenesis Mediated by γ-Aminobutyric Acid and Glutamate Signaling

Neurogenesis Mediated by γ-Aminobutyric Acid and Glutamate Signaling

Cell-Cycle Kinetics of Neocortical Precursors Are Influenced by Embryonic Thalamic Axons

Neuroprotection by endogenous and exogenous PACAP following stroke

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The PACAP Ligand/Receptor System Regulates Cerebral Cortical Neurogenesisa

Cited by 59 publications

References 53 publications

Neurogenesis Mediated by γ-Aminobutyric Acid and Glutamate Signaling

Neurogenesis Mediated by γ-Aminobutyric Acid and Glutamate Signaling

Cell-Cycle Kinetics of Neocortical Precursors Are Influenced by Embryonic Thalamic Axons

Neuroprotection by endogenous and exogenous PACAP following stroke

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The PACAP Ligand/Receptor System Regulates Cerebral Cortical Neurogenesis^a