Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G-protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole-cell patch clamp recordings were performed in rat brainstem slices from 9 to 17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (INa) and h-current (IH) in PPN neurons. TA (100 nM) reduced the blockade of INa (~ 50% reduction) and IH (~ 93% reduction) caused by leptin. Intracellular guanosine 5′-[β-thio]diphosphate trilithium salt (a G-protein inhibitor) significantly reduced the effect of leptin on INa(~ 60% reduction) but not on IH (~ 25% reduction). Intracellular GTPγS (a G-protein activator) reduced the effect of leptin on both INa (~ 80% reduction) and IH (~ 90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor- and G-protein dependent. We also found that leptin enhanced NMDA receptor-mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances. Beck et al. investigated the effects of leptin on the intrinsic properties of neurons from the pedunculopontine nucleus (PPN). Leptin reduced the amplitude of voltage-gated sodium (INa) and hyperpolarization-activated cyclic nucleotide-gated HCN (IH) channels. These effects were antagonized by a leptin receptor (OB-R) antagonist and by the G-protein antagonist GDPβ. Beck et al. investigated the effects of leptin on the intrinsic properties of neurons from the pedunculopontine nucleus (PPN). Leptin reduced the amplitude of voltage-gated sodium (INa) and hyperpolarization-activated cyclic nucleotide-gated HCN (IH) channels. These effects were antagonized by a leptin receptor (OB-R) antagonist and by the G-protein antagonist GDPβ. © 2013 International Society for Neurochemistry.

Registro:

Documento: Artículo
Título:Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons
Autor:Beck, P.; Mahaffey, S.; Urbano, F.J.; Garcia-Rill, E.
Filiación:Department of Neurobiology and Development Science, Center for Translational Neuroscience, University of Arkansas for Medical Sciences, 4301 West Markham St., Slot 847, Little Rock, AR 72205, United States
IFIBYNE, CONICET, University of Buenos Aires, Buenos Aires, Argentina
Palabras clave:arousal; GDPβ, GTPγS; hyperpolarization-activated cation current; sodium current; guanine nucleotide binding protein; leptin; leptin receptor; n methyl dextro aspartic acid receptor; proton pump; sodium channel; animal cell; animal tissue; article; brain nerve cell; brain slice; brain stem; controlled study; female; male; nonhuman; patch clamp; pedunculopontine tegmental nucleus; priority journal; protein function; rat; arousal; GDPβ, GTPγS; hyperpolarization-activated cation current; sodium current; Animals; Cyclic Nucleotide-Gated Cation Channels; Data Interpretation, Statistical; Excitatory Postsynaptic Potentials; Female; GTP-Binding Proteins; Immunohistochemistry; Leptin; Male; Membrane Potentials; Neurons; Patch-Clamp Techniques; Pedunculopontine Tegmental Nucleus; Population; Potassium Channels; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Sodium Channels; Rattus
Año:2013
Volumen:126
Número:6
Página de inicio:705
Página de fin:714
DOI: http://dx.doi.org/10.1111/jnc.12312
Título revista:Journal of Neurochemistry
Título revista abreviado:J. Neurochem.
ISSN:00223042
CODEN:JONRA
CAS:Cyclic Nucleotide-Gated Cation Channels; GTP-Binding Proteins, 3.6.1.-; Leptin; Potassium Channels; Receptors, N-Methyl-D-Aspartate; Sodium Channels; hyperpolarization-activated cation channel
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223042_v126_n6_p705_Beck

Referencias:

  • Ahima, R.S., Flier, J.S., Leptin (2000) Annu. Rev. Physiol., 62, pp. 413-437
  • Aldabal, L., Bahammam, A.S., Metabolic, endocrine, and immune consequences of sleep deprivation (2011) Open Respir. Med. J., 5, pp. 31-43
  • Aramakis, V.B., Bandrowski, A.E., Ashe, J.H., Activation of muscarinic receptors modulates NMDA receptor-mediated responses in auditory cortex (1997) Exp. Brain Res., 113, pp. 484-496
  • Beck, P., Urbano, F.J., Williams, D.K., Garcia-Rill, E., Effects of leptin on pedunculopontine nucleus (PPN) neurons (2013) J. Neural Transm., , [Epub ahead of print]
  • Bjorbaeck, C., Elmquist, J.K., Frantz, J.D., Shoelson, S.E., Flier, J.S., Identification of SOCS-3 as a potential mediator of central leptin resistance (1998) Mol. Cell, 1, pp. 619-625
  • Caldwell, D.F., Domino, E.F., Electroencephalographic and eye movement patterns during sleep in chronic schizophrenic patients (1967) Electroencephalogr. Clin. Neurophysiol., 22, pp. 414-420
  • Cizza, G., Ronsaville, D.S., Kleitz, H., Clinical subtypes of depression are associated with specific metabolic parameters and circadian endocrine profiles in women: The power study (2012) PLoS ONE, 7, pp. e28912
  • Cottrell, E.C., Cripps, R.L., Duncan, J.S., Barrett, P., Mercer, J.G., Herwig, A., Ozanne, S.E., Developmental changes in hypothalamic leptin receptor: Relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat (2009) Am. J. Physiol. Regul. Integr. Comp. Physiol., 296, pp. R631-R639
  • Datta, S., Prutzman, S.L., Novel role of brain stem pedunculopontine tegmental adenylyl cyclase in the regulation of spontaneous REM sleep in the freely moving rat (2005) J. Neurophysiol., 94, pp. 1928-1937
  • Deckleman, M.C., Dixon, L.B., Conley, R.R., Comorbid bulimia nervosa and schizophrenia (1997) Int. J. Eat. Disord., 22, pp. 101-105
  • Delorme, A., Makeig, S., EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis (2004) J. Neurosci. Methods, 134, pp. 9-21
  • Dixon, J.B., Dixon, M.E., Anderson, M.L., Schachter, L., O'Brien, P.E., Daytime sleepiness in the obese: Not as simple as obstructive sleep apnea (2007) Obesity (Silver Spring), 15, pp. 2504-2511
  • Durakoglugil, M., Irving, A.J., Harvey, J., Leptin induces a novel form of NMDA receptor-dependent long-term depression (2005) J. Neurochem., 95, pp. 396-405
  • Fukuda, M., Williams, K.W., Gautron, L., Elmquist, J.K., Induction of leptin resistance by activation of cAMP-Epac signaling (2011) Cell Metab., 13, pp. 331-339
  • Garcia-Rill, E., Charlesworth, A., Heister, D., Ye, M., Hayar, A., The developmental decrease in REM sleep: The role of transmitters and electrical coupling (2008) Sleep, 31, pp. 673-690
  • Garcia-Rill, E., Wallace-Huitt, T., Mennemeier, M., Charlesworth, A., Heister, D., Ye, M., Yates, C., Neuropharmacology of sleep and wakefulness (2009) Sleep Medicine Essentials, pp. 15-21. , in (Lee-Chiong T. L. ed), Wiley, New Jersey
  • Harvey, J., Leptin regulation of neuronal excitability and cognitive function (2007) Curr. Opin. Pharmacol., 7, pp. 643-647
  • Hille, B., Modulation of ion-channel function by G-protein-coupled receptors (1994) Trends Neurosci., 17, pp. 531-536
  • Israel, D.D., Sheffer-Babila, S., De Luca, C., Jo, Y.H., Liu, S.M., Xia, Q., Spergel, D.J., Chua, Jr.S.C., Effects of leptin and melanocortin signaling interactions on pubertal development and reproduction (2012) Endocrinology, 153, pp. 2408-2419
  • Jus, K., Bouchard, M., Jus, A., Villeneuve, A., Lachance, R., Sleep EEG studies in untreated long-term schizophrenic patients (1973) Arch. Gen. Psychiatry, 29, pp. 286-290
  • Krebs, D.L., Hilton, D.J., SOCS: Physiological suppressors of cytokine signaling (2000) J. Cell Sci., 113, pp. 2813-2819
  • Liu, S.B., Zhang, N., Guo, Y.Y., G-protein-coupled receptor 30 mediates rapid neuroprotective effects of estrogen via depression of NR2B-containing NMDA receptors (2012) J. Neurosci., 32, pp. 4887-4900
  • Luthi, A., McCormick, D.A., H-current: Properties of a neuronal and network pacemaker (1998) Neuron, 21, pp. 9-12
  • Moult, P.R., Harvey, J., Regulation of glutamate receptor trafficking by leptin (2009) Biochem. Soc. Trans., 37, pp. 1364-1368
  • O'Malley, D., Irving, A.J., Harvey, J., Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels (2005) FASEB J., 19, pp. 1917-1919
  • Perellõ, M., Zigman, J.M., The role of ghrelin in reward-based eating (2012) Biol. Psychiatry, 72, pp. 347-353
  • Ross, R.J., Bull, W.A., Sullivan, K.A., Caraff, S.N., Sleep disturbance as the hallmark of posttraumatic stress disorder (1989) Am. J. Psychiatry, 146, pp. 697-707
  • Sahu, A., Intracellular leptin-signaling pathways in hypothalamic neurons: The emerging role of phosphatidylinositol-3 kinase-phosphodiesterase-3B-cAMP pathway (2011) Neuroendocrinology, 93, pp. 201-210
  • Sentissi, O., Epelbaum, J., Olie, J.P., Poirier, M.F., Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: A review (2008) Schizophr. Bull., 34, pp. 1189-1199
  • Shanley, L.J., Irving, A.J., Harvey, J., Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity (2001) J. Neurosci., 21, pp. RC186
  • Shanley, L.J., O'Malley, D., Irving, A.J., Ashford, M.L., Harvey, J., Leptin inhibits epileptiform-like activity in rat hippocampal neurones via PI 3-kinase-driven activation of BK channels (2002) J. Physiol., 545, pp. 933-944
  • Shouse, M.N., Siegel, J.M., Pontine regulation of REM sleep components in cats: Integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep (1992) Brain Res., 571, pp. 50-63
  • Shpilman, M., Niv-Spector, L., Katz, M., Varol, C., Solomon, G., Ayalon-Soffer, M., Boder, E., Gertler, A., Development and characterization of high affinity leptins and leptin antagonists (2011) J. Biol. Chem., 286, pp. 4429-4442
  • Simon, C., Hayar, A., Garcia-Rill, E., Responses of developing pedunculopontine neurons to glutamate receptor agonists (2011) J. Neurophysiol., 105, pp. 1918-1931
  • Sinton, M.M., Goldschmidt, A.B., Aspen, V., Theim, K.R., Stein, R.I., Saelens, B.E., Epstein, L.H., Wilfley, D.E., Psychosocial correlates of shape and weight concerns in overweight pre-adolescents (2012) J. Youth Adolesc., 41, pp. 67-75
  • Spiegel, K., Knutson, K., Leproult, R., Tasali, E., Van, C.E., Sleep loss: A novel risk factor for insulin resistance and Type 2 diabetes (2005) J. Appl. Physiol., 99, pp. 2008-2019
  • Steriade, M., Datta, S., Pare, D., Oakson, G., Curro Dossi, R.C., Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems (1990) J. Neurosci., 10, pp. 2541-2559
  • Taheri, S., Lin, L., Austin, D., Young, T., Mignot, E., Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index (2004) PLoS Med., 1, pp. e62
  • Tong, H., Gibb, A.J., Dopamine D1 receptor inhibition of NMDA receptor currents mediated by tyrosine kinase-dependent receptor trafficking in neonatal rat striatum (2008) J. Physiol., 586, pp. 4693-4707
  • Vanoye, C.G., Kunic, J.D., Ehring, G.R., George, Jr.A.L., Mechanism of sodium channel NaV1.9 potentiation by G-protein signaling (2013) J. Gen. Physiol., 141, pp. 193-202
  • Vgontzas, A.N., Bixler, E.O., Tan, T.L., Kantner, D., Martin, L.F., Kales, A., Obesity without sleep apnea is associated with daytime sleepiness (1998) Arch. Intern. Med., 158, pp. 1333-1337

Citas:

---------- APA ----------
Beck, P., Mahaffey, S., Urbano, F.J. & Garcia-Rill, E. (2013) . Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons. Journal of Neurochemistry, 126(6), 705-714.
http://dx.doi.org/10.1111/jnc.12312
---------- CHICAGO ----------
Beck, P., Mahaffey, S., Urbano, F.J., Garcia-Rill, E. "Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons" . Journal of Neurochemistry 126, no. 6 (2013) : 705-714.
http://dx.doi.org/10.1111/jnc.12312
---------- MLA ----------
Beck, P., Mahaffey, S., Urbano, F.J., Garcia-Rill, E. "Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons" . Journal of Neurochemistry, vol. 126, no. 6, 2013, pp. 705-714.
http://dx.doi.org/10.1111/jnc.12312
---------- VANCOUVER ----------
Beck, P., Mahaffey, S., Urbano, F.J., Garcia-Rill, E. Role of G-proteins in the effects of leptin on pedunculopontine nucleus neurons. J. Neurochem. 2013;126(6):705-714.
http://dx.doi.org/10.1111/jnc.12312