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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Detalles Bibliográficos
Autores principales: Beck, P., Urbano, F.J., Williams, D.K., Garcia-Rill, E.
Formato: JOUR
Materias:
Arousal
Hyperpolarization-activated cation current
Sodium current
leptin
agents interacting with transmitter, hormone or drug receptors
ion channel
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
nonparametric test
patch clamp technique
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
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_03009564_v120_n7_p1027_Beck
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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