New Insights into the Central PACAPergic System from the Phenotypes in PACAP‐ and PACAP Receptor‐Knockout Mice

Hashimoto, Hitoshi; Shintani, Norihito; Baba, Akemichi

doi:10.1196/annals.1317.038

Cited by 96 publications

(61 citation statements)

References 82 publications

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“…Consistent with this, a gradient of PACAP rapidly induces robust cAMP production in a receptive axonal growth cone and this evokes chemoattraction (Fig. 2 B, D) (Hashimoto et al, 2006). Additionally, axonal attraction to an extracellular gradient of PACAP is disrupted when cAMP is elevated globally (Guirland et al, 2003).…”

Section: Discussionsupporting

confidence: 52%

“…membrane adenylyl cyclase through a G-protein coupled receptor-dependent pathway (Hashimoto et al, 2006). In neurons maintained at 0.08 or 2.5 ng/ml NGF, PACAP exposure induced a robust increase in cellular cAMP levels in both the presence and absence of the phosphodiesterase inhibitor IBMX, which inhibits the breakdown of cAMP (Fig.…”

Section: Netrin-1 Does Not Elevate Camp Levels In Embryonic Drg Neuronsmentioning

confidence: 99%

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Soluble Adenylyl Cyclase Is Not Required for Axon Guidance to Netrin-1

Moore

Sun²,

Xie³

et al. 2008

J. Neurosci.

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During development, axons are directed to their targets by extracellular guidance cues. The axonal response to the guidance cue netrin-1 is profoundly influenced by the concentration of cAMP within the growth cone. In some cases, cAMP affects the sensitivity of the growth cone to netrin-1, whereas in others it changes the response to netrin-1 from attraction to repulsion. The effects of cAMP on netrin-1 action are well accepted, but the critical issue of whether cAMP production is activated by a netrin-1 induced signaling cascade remains uncertain. A previous report has suggested that axon guidance in response to netrin-1 requires cAMP production mediated by soluble adenyl cyclase (sAC). We have used genetic, molecular and biochemical strategies to assess this issue. Surprisingly, we found only extremely weak expression of sAC in embryonic neurons and determined that, under conditions where netrin-1 directs axonal pathfinding, exposure to netrin-1 does not alter cAMP levels. Furthermore, although netrin-1-deficient mice exhibit major axon guidance defects, we show that pathfinding is normal in sAC-null mice. Therefore, although cAMP can alter the response of axons to netrin-1, we conclude that netrin-1 does not alter cAMP levels in axons attracted by this cue, and that sAC is not required for axon attraction to netrin-1.

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Section: Discussionsupporting

confidence: 52%

Section: Netrin-1 Does Not Elevate Camp Levels In Embryonic Drg Neuronsmentioning

confidence: 99%

Soluble Adenylyl Cyclase Is Not Required for Axon Guidance to Netrin-1

Moore

Sun²,

Xie³

et al. 2008

J. Neurosci.

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“…Of these, functions in the VMH are best described for BDNF, in which it acts as a satiety factor downstream of melanocortin signaling . PACAP signaling is proposed to regulate the sympathoadrenal axis affecting the release of adrenal steroids (Hashimoto et al, 2006), and substance P release from ER-positive VMH neurons is proposed to affect sexual behavior (Daniels et al, 2003). Other known adult VMH peptides, such as enkephalin, cholecystokinin (CCK ), and somatostatin, were not enriched in the neonatal VMH, but some were found at much higher levels in P21 hypothalami (F. Y.…”

Section: The Neonatal Mouse Vmh Transcriptomementioning

confidence: 99%

The Neonatal Ventromedial Hypothalamus Transcriptome Reveals Novel Markers with Spatially Distinct Patterning

Kurrasch¹,

Cheung²,

Lee³

et al. 2007

J. Neurosci.

155

151

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The ventromedial hypothalamus (VMH) is a distinct morphological nucleus involved in feeding, fear, thermoregulation, and sexual activity. It is essentially unknown how VMH circuits underlying these innate responses develop, in part because the VMH remains poorly defined at a cellular and molecular level. Specifically, there is a paucity of cell-type-specific genetic markers with which to identify neuronal subgroups and manipulate development and signaling in vivo. Using gene profiling, we now identify ϳ200 genes highly enriched in neonatal (postnatal day 0) mouse VMH tissue. Analyses of these VMH markers by real or virtual (Allen Brain Atlas; http:// www.brain-map.org) experiments revealed distinct regional patterning within the newly formed VMH. Top neonatal markers include transcriptional regulators such as Vgll2, SF-1, Sox14, Satb2, Fezf1, Dax1, Nkx2-2, and COUP-TFII, but interestingly, the highest expressed VMH transcript, the transcriptional coregulator Vgll2, is completely absent in older animals. Collective results from zebrafish knockdown experiments and from cellular studies suggest that a subset of these VMH markers will be important for hypothalamic development and will be downstream of SF-1, a critical factor for normal VMH differentiation. We show that at least one VMH marker, the AT-rich binding protein Satb2, was responsive to the loss of leptin signaling (Lep ob/ob ) at postnatal day 0 but not in the adult, suggesting that some VMH transcriptional programs might be influenced by fetal or early postnatal environments. Our study describing this comprehensive "VMH transcriptome" provides a novel molecular toolkit to probe further the genetic basis of innate neuroendocrine behavioral responses.

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“…52 Animal experimental models have proposed that PACAP might have a role in central pain transmission. 53 Capsaicin elevates PACAP in rat cerebrospinal fluid in vivo, 54 suggesting that PACAP may be released from activated C-fibers in the spinal cord. In PACAP gene knockout mice (Adcyap1 Ϫ/Ϫ ), inflammatory pain disappears 55 and PACAP promotes the functional coupling of neuronal NO-synthase to NMDA receptors.…”

Section: The Central Actions Of Pacapmentioning

confidence: 99%

The PACAP Receptor: A Novel Target for Migraine Treatment

2010

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Summary:The origin of migraine pain has not yet been clarified, but accumulating data point to neuropeptides present in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in sensory trigeminal neurons and may modulate nociception at different levels of the nervous system. Human experimental studies have shown that PACAP-38 infusion induces marked dilatation of extracerebral vessels and delayed migraine-like attacks in migraine patients. PACAP selectively activates the PAC 1 receptor, which suggests a possible signaling pathway implicated in migraine pain. This review summarizes the current evidence supporting the involvement of PACAP in migraine pathophysiology and the PAC 1 receptor as a possible novel target for migraine treatment.

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New Insights into the Central PACAPergic System from the Phenotypes in PACAP‐ and PACAP Receptor‐Knockout Mice

Cited by 96 publications

References 82 publications

Soluble Adenylyl Cyclase Is Not Required for Axon Guidance to Netrin-1

Soluble Adenylyl Cyclase Is Not Required for Axon Guidance to Netrin-1

The Neonatal Ventromedial Hypothalamus Transcriptome Reveals Novel Markers with Spatially Distinct Patterning

The PACAP Receptor: A Novel Target for Migraine Treatment

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