Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons

Human postmortem studies reported increased expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Bipolar disorder is characterized by sleep dysregulation, suggesting a rol...

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Autores principales: D'Onofrio, S., Urbano, F.J., Messias, E., Garcia-Rill, E.
Formato: JOUR
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_2051817X_v4_n6_p1_DOnofrio
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spelling todo:paper_2051817X_v4_n6_p1_DOnofrio2023-10-03T16:38:53Z Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons D'Onofrio, S. Urbano, F.J. Messias, E. Garcia-Rill, E. Bipolar disorder Gamma band activity Sleep/wake calcium channel N type frequenin calcium sensor proteins lithium derivative neuroleptic agent neuronal calcium sensor neuropeptide recombinant protein voltage-dependent calcium channel (P-Q type) animal calcium signaling channel gating dose response drug effects female gamma rhythm in vitro study kinetics male membrane potential metabolism nerve cell newborn pedunculopontine tegmental nucleus Sprague Dawley rat Animals Animals, Newborn Antipsychotic Agents Calcium Channels, N-Type Calcium Signaling Dose-Response Relationship, Drug Female Gamma Rhythm In Vitro Techniques Ion Channel Gating Kinetics Lithium Compounds Male Membrane Potentials Neuronal Calcium-Sensor Proteins Neurons Neuropeptides Pedunculopontine Tegmental Nucleus Rats, Sprague-Dawley Recombinant Proteins Human postmortem studies reported increased expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Lithium (Li+) has been shown to effectively treat the mood disturbances in bipolar disorder patients and was proposed to act by inhibiting the interaction between NCS-1 and inositol 1,4,5-triphosphate receptor protein (InsP3R). NCS-1 is known to enhance the activity of InsP3R, and of Ca2+-mediated gamma oscillatory activity in the pedunculopontine nucleus (PPN), part of the RAS. This study aimed to determine the nature of some of the intracellular mechanisms of Li+ on rat PPN cells and to identify the interaction between Li+ and NCS-1. Since Li+ has been shown to act by inhibiting the enhancing effects of NCS-1, we tested the hypothesis that Li+ would reduced the effects of overexpression of NCS-1 and prevent the downregulation of gamma band activity. Li+ decreased gamma oscillation frequency and amplitude by downregulating Ca2+ channel activity, whereas NCS-1 reduced the effect of Li+ on Ca2+ currents. These effects were mediated by a G-protein overinhibition of Ca2+ currents. These results suggest that Li+ affected intracellular pathways involving the activation of voltage-gated Ca2+ channels mediated by an intracellular mechanism involving voltage-dependent activation of G proteins, thereby normalizing gamma band oscillations mediated by P/Q-type calcium channels modulated by NCS-1. © 2016 Published by the American Physiological Society and The Physiological Society. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_2051817X_v4_n6_p1_DOnofrio
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Bipolar disorder
Gamma band activity
Sleep/wake
calcium channel N type
frequenin calcium sensor proteins
lithium derivative
neuroleptic agent
neuronal calcium sensor
neuropeptide
recombinant protein
voltage-dependent calcium channel (P-Q type)
animal
calcium signaling
channel gating
dose response
drug effects
female
gamma rhythm
in vitro study
kinetics
male
membrane potential
metabolism
nerve cell
newborn
pedunculopontine tegmental nucleus
Sprague Dawley rat
Animals
Animals, Newborn
Antipsychotic Agents
Calcium Channels, N-Type
Calcium Signaling
Dose-Response Relationship, Drug
Female
Gamma Rhythm
In Vitro Techniques
Ion Channel Gating
Kinetics
Lithium Compounds
Male
Membrane Potentials
Neuronal Calcium-Sensor Proteins
Neurons
Neuropeptides
Pedunculopontine Tegmental Nucleus
Rats, Sprague-Dawley
Recombinant Proteins
spellingShingle Bipolar disorder
Gamma band activity
Sleep/wake
calcium channel N type
frequenin calcium sensor proteins
lithium derivative
neuroleptic agent
neuronal calcium sensor
neuropeptide
recombinant protein
voltage-dependent calcium channel (P-Q type)
animal
calcium signaling
channel gating
dose response
drug effects
female
gamma rhythm
in vitro study
kinetics
male
membrane potential
metabolism
nerve cell
newborn
pedunculopontine tegmental nucleus
Sprague Dawley rat
Animals
Animals, Newborn
Antipsychotic Agents
Calcium Channels, N-Type
Calcium Signaling
Dose-Response Relationship, Drug
Female
Gamma Rhythm
In Vitro Techniques
Ion Channel Gating
Kinetics
Lithium Compounds
Male
Membrane Potentials
Neuronal Calcium-Sensor Proteins
Neurons
Neuropeptides
Pedunculopontine Tegmental Nucleus
Rats, Sprague-Dawley
Recombinant Proteins
D'Onofrio, S.
Urbano, F.J.
Messias, E.
Garcia-Rill, E.
Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
topic_facet Bipolar disorder
Gamma band activity
Sleep/wake
calcium channel N type
frequenin calcium sensor proteins
lithium derivative
neuroleptic agent
neuronal calcium sensor
neuropeptide
recombinant protein
voltage-dependent calcium channel (P-Q type)
animal
calcium signaling
channel gating
dose response
drug effects
female
gamma rhythm
in vitro study
kinetics
male
membrane potential
metabolism
nerve cell
newborn
pedunculopontine tegmental nucleus
Sprague Dawley rat
Animals
Animals, Newborn
Antipsychotic Agents
Calcium Channels, N-Type
Calcium Signaling
Dose-Response Relationship, Drug
Female
Gamma Rhythm
In Vitro Techniques
Ion Channel Gating
Kinetics
Lithium Compounds
Male
Membrane Potentials
Neuronal Calcium-Sensor Proteins
Neurons
Neuropeptides
Pedunculopontine Tegmental Nucleus
Rats, Sprague-Dawley
Recombinant Proteins
description Human postmortem studies reported increased expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Lithium (Li+) has been shown to effectively treat the mood disturbances in bipolar disorder patients and was proposed to act by inhibiting the interaction between NCS-1 and inositol 1,4,5-triphosphate receptor protein (InsP3R). NCS-1 is known to enhance the activity of InsP3R, and of Ca2+-mediated gamma oscillatory activity in the pedunculopontine nucleus (PPN), part of the RAS. This study aimed to determine the nature of some of the intracellular mechanisms of Li+ on rat PPN cells and to identify the interaction between Li+ and NCS-1. Since Li+ has been shown to act by inhibiting the enhancing effects of NCS-1, we tested the hypothesis that Li+ would reduced the effects of overexpression of NCS-1 and prevent the downregulation of gamma band activity. Li+ decreased gamma oscillation frequency and amplitude by downregulating Ca2+ channel activity, whereas NCS-1 reduced the effect of Li+ on Ca2+ currents. These effects were mediated by a G-protein overinhibition of Ca2+ currents. These results suggest that Li+ affected intracellular pathways involving the activation of voltage-gated Ca2+ channels mediated by an intracellular mechanism involving voltage-dependent activation of G proteins, thereby normalizing gamma band oscillations mediated by P/Q-type calcium channels modulated by NCS-1. © 2016 Published by the American Physiological Society and The Physiological Society.
format JOUR
author D'Onofrio, S.
Urbano, F.J.
Messias, E.
Garcia-Rill, E.
author_facet D'Onofrio, S.
Urbano, F.J.
Messias, E.
Garcia-Rill, E.
author_sort D'Onofrio, S.
title Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
title_short Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
title_full Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
title_fullStr Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
title_full_unstemmed Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
title_sort lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
url http://hdl.handle.net/20.500.12110/paper_2051817X_v4_n6_p1_DOnofrio
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AT messiase lithiumdecreasestheeffectsofneuronalcalciumsensorprotein1inpedunculopontineneurons
AT garciarille lithiumdecreasestheeffectsofneuronalcalciumsensorprotein1inpedunculopontineneurons
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