Effects of leptin on pedunculopontine nucleus (PPN) neurons
Leptin, a hormone that regulates appetite and energy expenditure, is increased in obese individuals, although these individuals often exhibit leptin resistance. Obesity is characterized by sleep/wake disturbances, such as excessive daytime sleepiness, increased REM sleep, increased nighttime arousal...
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todo:paper_03009564_v120_n7_p1027_Beck2023-10-03T15:18:01Z Effects of leptin on pedunculopontine nucleus (PPN) neurons Beck, P. Urbano, F.J. Williams, D.K. Garcia-Rill, E. Arousal Hyperpolarization-activated cation current Sodium current leptin agents interacting with transmitter, hormone or drug receptors ion channel leptin action potential animal cell arousal article controlled study nerve cell newborn nonhuman patch clamp pedunculopontine tegmental nucleus priority journal rat REM sleep sleep disorder sodium conductance sodium current animal biophysics channel gating cytology dose response drug effects electrostimulation female in vitro study male nerve cell nonparametric test patch clamp technique pedunculopontine tegmental nucleus physiology pregnancy Sprague Dawley rat Action Potentials Animals Animals, Newborn Biophysical Processes Biophysics Dose-Response Relationship, Drug Electric Stimulation Female In Vitro Techniques Ion Channel Gating Ion Channels Leptin Male Neurons Neurotransmitter Agents Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Pregnancy Rats Rats, Sprague-Dawley Statistics, Nonparametric Leptin, a hormone that regulates appetite and energy expenditure, is increased in obese individuals, although these individuals often exhibit leptin resistance. Obesity is characterized by sleep/wake disturbances, such as excessive daytime sleepiness, increased REM sleep, increased nighttime arousals, and decreased percentage of total sleep time. Several studies have shown that short sleep duration is highly correlated with decreased leptin levels in both animal and human models. Arousal and rapid eye movement (REM) sleep are regulated by the cholinergic arm of the reticular activating system, the pedunculopontine nucleus (PPN). The goal of this project was to determine the role of leptin in the PPN, and thus in obesity-related sleep disorders. Whole-cell patch-clamp recordings were conducted on PPN neurons in 9- to 17-day-old rat brainstem slices. Leptin decreased action potential (AP) amplitude, AP frequency, and h-current (I H). These findings suggest that leptin causes a blockade of Na+ channels. Therefore, we conducted an experiment to test the effects of leptin on Na+ conductance. To determine the average voltage dependence of this conductance, results from each cell were equally weighted by expressing conductance as a fraction of the maximum conductance in each cell. I Na amplitude was decreased in a dose-dependent manner, suggesting a direct effect of leptin on these channels. The average decrease in Na+ conductance by leptin was ~40 %. We hypothesize that leptin normally decreases activity in the PPN by reducing I H and I Na currents, and that in states of leptin dysregulation (i.e., leptin resistance) this effect may be blunted, therefore causing increased arousal and REM sleep drive, and ultimately leading to sleep-related disorders. © 2012 Springer-Verlag Wien. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03009564_v120_n7_p1027_Beck |
| institution |
Universidad de Buenos Aires |
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I-28 |
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R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Arousal Hyperpolarization-activated cation current Sodium current leptin agents interacting with transmitter, hormone or drug receptors ion channel leptin action potential animal cell arousal article controlled study nerve cell newborn nonhuman patch clamp pedunculopontine tegmental nucleus priority journal rat REM sleep sleep disorder sodium conductance sodium current animal biophysics channel gating cytology dose response drug effects electrostimulation female in vitro study male nerve cell nonparametric test patch clamp technique pedunculopontine tegmental nucleus physiology pregnancy Sprague Dawley rat Action Potentials Animals Animals, Newborn Biophysical Processes Biophysics Dose-Response Relationship, Drug Electric Stimulation Female In Vitro Techniques Ion Channel Gating Ion Channels Leptin Male Neurons Neurotransmitter Agents Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Pregnancy Rats Rats, Sprague-Dawley Statistics, Nonparametric |
| spellingShingle |
Arousal Hyperpolarization-activated cation current Sodium current leptin agents interacting with transmitter, hormone or drug receptors ion channel leptin action potential animal cell arousal article controlled study nerve cell newborn nonhuman patch clamp pedunculopontine tegmental nucleus priority journal rat REM sleep sleep disorder sodium conductance sodium current animal biophysics channel gating cytology dose response drug effects electrostimulation female in vitro study male nerve cell nonparametric test patch clamp technique pedunculopontine tegmental nucleus physiology pregnancy Sprague Dawley rat Action Potentials Animals Animals, Newborn Biophysical Processes Biophysics Dose-Response Relationship, Drug Electric Stimulation Female In Vitro Techniques Ion Channel Gating Ion Channels Leptin Male Neurons Neurotransmitter Agents Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Pregnancy Rats Rats, Sprague-Dawley Statistics, Nonparametric Beck, P. Urbano, F.J. Williams, D.K. Garcia-Rill, E. Effects of leptin on pedunculopontine nucleus (PPN) neurons |
| topic_facet |
Arousal Hyperpolarization-activated cation current Sodium current leptin agents interacting with transmitter, hormone or drug receptors ion channel leptin action potential animal cell arousal article controlled study nerve cell newborn nonhuman patch clamp pedunculopontine tegmental nucleus priority journal rat REM sleep sleep disorder sodium conductance sodium current animal biophysics channel gating cytology dose response drug effects electrostimulation female in vitro study male nerve cell nonparametric test patch clamp technique pedunculopontine tegmental nucleus physiology pregnancy Sprague Dawley rat Action Potentials Animals Animals, Newborn Biophysical Processes Biophysics Dose-Response Relationship, Drug Electric Stimulation Female In Vitro Techniques Ion Channel Gating Ion Channels Leptin Male Neurons Neurotransmitter Agents Patch-Clamp Techniques Pedunculopontine Tegmental Nucleus Pregnancy Rats Rats, Sprague-Dawley Statistics, Nonparametric |
| description |
Leptin, a hormone that regulates appetite and energy expenditure, is increased in obese individuals, although these individuals often exhibit leptin resistance. Obesity is characterized by sleep/wake disturbances, such as excessive daytime sleepiness, increased REM sleep, increased nighttime arousals, and decreased percentage of total sleep time. Several studies have shown that short sleep duration is highly correlated with decreased leptin levels in both animal and human models. Arousal and rapid eye movement (REM) sleep are regulated by the cholinergic arm of the reticular activating system, the pedunculopontine nucleus (PPN). The goal of this project was to determine the role of leptin in the PPN, and thus in obesity-related sleep disorders. Whole-cell patch-clamp recordings were conducted on PPN neurons in 9- to 17-day-old rat brainstem slices. Leptin decreased action potential (AP) amplitude, AP frequency, and h-current (I H). These findings suggest that leptin causes a blockade of Na+ channels. Therefore, we conducted an experiment to test the effects of leptin on Na+ conductance. To determine the average voltage dependence of this conductance, results from each cell were equally weighted by expressing conductance as a fraction of the maximum conductance in each cell. I Na amplitude was decreased in a dose-dependent manner, suggesting a direct effect of leptin on these channels. The average decrease in Na+ conductance by leptin was ~40 %. We hypothesize that leptin normally decreases activity in the PPN by reducing I H and I Na currents, and that in states of leptin dysregulation (i.e., leptin resistance) this effect may be blunted, therefore causing increased arousal and REM sleep drive, and ultimately leading to sleep-related disorders. © 2012 Springer-Verlag Wien. |
| format |
JOUR |
| author |
Beck, P. Urbano, F.J. Williams, D.K. Garcia-Rill, E. |
| author_facet |
Beck, P. Urbano, F.J. Williams, D.K. Garcia-Rill, E. |
| author_sort |
Beck, P. |
| title |
Effects of leptin on pedunculopontine nucleus (PPN) neurons |
| title_short |
Effects of leptin on pedunculopontine nucleus (PPN) neurons |
| title_full |
Effects of leptin on pedunculopontine nucleus (PPN) neurons |
| title_fullStr |
Effects of leptin on pedunculopontine nucleus (PPN) neurons |
| title_full_unstemmed |
Effects of leptin on pedunculopontine nucleus (PPN) neurons |
| title_sort |
effects of leptin on pedunculopontine nucleus (ppn) neurons |
| url |
http://hdl.handle.net/20.500.12110/paper_03009564_v120_n7_p1027_Beck |
| work_keys_str_mv |
AT beckp effectsofleptinonpedunculopontinenucleusppnneurons AT urbanofj effectsofleptinonpedunculopontinenucleusppnneurons AT williamsdk effectsofleptinonpedunculopontinenucleusppnneurons AT garciarille effectsofleptinonpedunculopontinenucleusppnneurons |
| _version_ |
1807315740088336384 |