Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine Neurons<i>In Vivo</i>and<i>In Vitro</i>: A Proposed Role during Glycemic Challenges

Khan, Arshad M.; Ponzio, Todd A.; Sanchez‐Watts, Graciela; Stanley, B. Glenn; Hatton, Glenn I.; Watts, Alan G.

doi:10.1523/jneurosci.0873-07.2007

Cited by 57 publications

(80 citation statements)

References 96 publications

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“…Paradoxically, the behavioral analyses show that the suppression of food intake by hindbrain Ex-4 delivery is not observed until 3 h postadministration, an effect dependent upon an increase in PI3K activation, translocation of Akt to the cell membrane, and presumably the suppression of membranebound Akt phosphorylation. Similar time course discrepancies for other intracellular signaling cascades between tissue lysates and physiological/behavioral feeding responses are reported for GLP-1R (26) and for other anorectic ligands acting within the brain (36,47,52,62). Moreover, hindbrain administration of TCN produced an increase in food intake 1 h postinjection (the earliest time point measured), indicating that a basal level of Akt activity within the hindbrain is required to maintain normal homeostatic food intake.…”

Section: Discussionsupporting

confidence: 61%

Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt

Rupprecht

Mietlicki‐Baase

Zimmer

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) expressed in the nucleus tractus solitarius (NTS) are physiologically required for the control of feeding. Recently, NTS GLP-1R-mediated suppression of feeding was shown to occur via a rapid PKA-induced suppression of AMPK and activation of MAPK signaling. Unknown are the additional intracellular signaling pathways that account for the long-term hypophagic effects of GLP-1R activation. Because cAMP/PKA activity can promote PI3K/PIP3-dependent translocation of Akt to the plasma membrane, we hypothesize that hindbrain GLP-1R-mediated control of feeding involves a PI3K-Akt-dependent pathway. Importantly, the novel evidence presented here challenges the dogmatic view that PI3K phosphorylation results in an obligatory activation of Akt and instead supports a growing body of literature showing that activation of cAMP/PKA can inhibit Akt phosphorylation at the plasma membrane. Behavioral data show that inhibition of hindbrain PI3K activity by a fourth icv administration of LY-294002 (3.07 μg) attenuated the food intake- and body weight-suppressive effects of a fourth icv administration of the GLP-1R agonist exendin-4 (0.3 μg) in rats. Hindbrain administration of triciribine (10 μg), an inhibitor of PIP3-dependent translocation of Akt to the cell membrane, also attenuated the intake-suppressive effects of a fourth icv injection of exendin-4. Immunoblot analyses of ex vivo NTS tissue lysates and in vitro GLP-1R-expressing neurons (GT1-7) support the behavioral findings and show that GLP-1R activation decreases phosphorylation of Akt in a time-dependent fashion. Current data reveal the requirement of PI3K activation, PIP3-dependent translocation of Akt to the plasma membrane, and suppression in phosphorylation of membrane-bound Akt to mediate the food intake-suppressive effects of hindbrain GLP-1R activation.

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Section: Discussionsupporting

confidence: 61%

Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt

Rupprecht

Mietlicki‐Baase

Zimmer

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…modulate ERK activity, for their ability to alter ISF Aβ levels in vivo (27)(28)(29)(30). Treatment with BDNF, a TrkB receptor ligand, or norepinephrine, a similar neurotransmitter to serotonin, did not change ISF Aβ levels after direct administration to the hippocampus (Fig.…”

Section: Serotonergic Regulation Of Isf Aβ Does Not Require Actionmentioning

confidence: 94%

Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans

Cirrito

Disabato²,

Restivo³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

300

307

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Aggregation of amyloid-β (Aβ) as toxic oligomers and amyloid plaques within the brain appears to be the pathogenic event that initiates Alzheimer's disease (AD) lesions. One therapeutic strategy has been to reduce Aβ levels to limit its accumulation. Activation of certain neurotransmitter receptors can regulate Aβ metabolism. We assessed the ability of serotonin signaling to alter brain Aβ levels and plaques in a mouse model of AD and in humans. In mice, brain interstitial fluid (ISF) Aβ levels were decreased by 25% following administration of several selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Similarly, direct infusion of serotonin into the hippocampus reduced ISF Aβ levels. Serotonindependent reductions in Aβ were reversed if mice were pretreated with inhibitors of the extracellular regulated kinase (ERK) signaling cascade. Chronic treatment with an SSRI, citalopram, caused a 50% reduction in brain plaque load in mice. To test whether serotonin signaling could impact Aβ plaques in humans, we retrospectively compared brain amyloid load in cognitively normal elderly participants who were exposed to antidepressant drugs within the past 5 y to participants who were not. Antidepressant-treated participants had significantly less amyloid load as quantified by positron emission tomography (PET) imaging with Pittsburgh Compound B (PIB). Cumulative time of antidepressant use within the 5-y period preceding the scan correlated with less plaque load. These data suggest that serotonin signaling was associated with less Aβ accumulation in cognitively normal individuals.microdialysis | selective serotonin reuptake inhibitor antidepressants | late-life depression A myloid-β (Aβ) dysregulation appears to initiate the pathogenesis of Alzheimer's disease (AD) with a cascade of downstream factors that exacerbate and propagate neuronal injury (1). Aβ can accumulate as toxic plaques and soluble oligomers in the brains of individuals with AD a decade or more before the initial symptoms are identified (2). The concentration of Aβ is a critical factor determining if and when it will aggregate into these toxic structures; high concentrations of Aβ are more prone to convert from its normal soluble form into these multimeric conformations (3). Aβ is formed within neurons by sequential cleavage of the amyloid precursor protein (APP) by two enzymes, β-secretase and then γ-secretase. Alternatively, α-secretase can cleave APP within the Aβ sequence, which precludes the peptide from being formed at all. The enzymes and mechanisms that produce Aβ have been well characterized; however, the mechanisms that regulate Aβ production and levels are only partly understood. Understanding the cellular processes that regulate Aβ levels may provide greater insight into disease pathogenesis and suggest new avenues to treat or prevent AD.Synaptic activity is one key regulator of brain Aβ production. Depolarization and subsequent synaptic transmission causes Aβ to be produced presynaptically and then secreted into the brain extracel...

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“…CRH promoter contains cis-acting elements among those the cAMP-response element (CRE) is of the highest significance in stress-initiated CRH transcription (Kovacs & Sawchenko 1996b, Seasholtz et al 1991, Seasholtz et al 1988 . This site integrates cAMP-PKA (Majzoub et al 1993), MAPK -ERK 1/2 (Khan et al 2011, Khan et al 2007, PKC (Majzoub et al 1993) and intracellular Ca 2+ signaling via phosphorylation of CREB (Khan et al 2011, Kovacs & Sawchenko 1996a). This relatively simple scenario of CRH regulation is complicated by several factors.…”

Section: Regulation Of Hypothalamic Crh Transcriptionmentioning

confidence: 99%

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

Kovács

2013

Journal of Chemical Neuroanatomy

105

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Two major and mutually interconnected brain systems are recruited during stress reaction. One is the hypothalamic paraventricular nucleus (PVH) and the second is the extended amygdala. PVH governs the neuroendocrine stress response while CeA regulates most of the autonomic and behavioral stress reactions. The common neurohormonal mediator of these responses is the corticotropin-releasing hormone, CRH, which is expressed in both centers. CRH belongs to a larger family of neuropeptides that also includes urocortins 1, 2, and 3 all have different affinity towards the two types of CRHR receptors and have been implicated in regulation of stress and HPA axis activity. One functionally relevant aspect of CRH systems is their differential regulation by glucocorticoids. While corticosterone inhibits CRH transcription in the PVH, stress-induced glucocorticoids stimulate CRH expression in the extended amygdala. This review summarizes past and recent findings related to CRH gene regulation and its involvement in the neuroendocrine, autonomic and behavioral stress reaction.Key words: Corticotropin-releasing hormone, paraventricular nucleus, central amygdala, bed nucleus of stria terminalis, corticosterone, cAMP-response element.

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Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

Cited by 57 publications

References 96 publications

Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt

Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt

Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

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