Noradrenaline acting on α1-adrenoceptor mediates REM sleep deprivation-induced increased membrane potential in rat brain synaptosomes

School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Neurochemistry International (Impact Factor: 3.09). 03/2008; 52(4-5):734-40. DOI: 10.1016/j.neuint.2007.09.002
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ABSTRACT We hypothesized that one of the functions of REM sleep is to maintain brain excitability and therefore, REM sleep deprivation is likely to modulate neuronal transmembrane potential; however, so far there was no direct evidence to support the claim. In this study a cationic dye, 3,3'-diethylthiacarbocyanine iodide was used to estimate the potential in synaptosomal samples prepared from control and REM sleep deprived rat brains. The activity of Na-K-ATPase that maintains the transmembrane potential was also estimated in the same sample. Further, the roles of noradrenaline and alpha1-adrenoceptor in mediating the responses were studied both in vivo as well as in vitro. Rats were REM sleep deprived for 4 days by the classical flower-pot method; large platform and recovery controls were carried out in addition to free-moving control. The fluorescence intensity increased in samples prepared from REM sleep deprived rat brain as compared to control, which reflected synaptosomal depolarization after deprivation. The Na-K-ATPase activity also increased in the same deprived sample. Furthermore, both the effects were mediated by noradrenaline acting on alpha1-adrenoceptors in the brain. This is the first direct evidence showing that REM sleep deprivation indeed increased neuronal depolarization, which is the likely cause for increased brain excitability, thus supporting our hypothesis and the effect was mediated by noradrenaline acting through the alpha1-adrenoceptor.

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Available from: Gitanjali Das, Aug 20, 2015
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    • "Although PGO waves cannot be recorded in humans, PGO-like field potentials have been recorded in humans (Lim et al., 2007), and increased activity in both lateral geniculate body and occipital cortex has been reported with Positron Emission Tomography (PET) in humans (Hong et al., 1995; Peigneux et al., 2001). It has been shown that REM-D in rats increases the activity of Na-K ATPase enzyme (Gulyani and Mallick, 1993), leading to increased excitability of neurons (Das and Mallick, 2008). The usual inhibitory period observed after repetitive auditory stimulation is shortened after REM-D in evoked potentials (Dewson et al., 1967) and in pontine neurons (Mallick et al., 1991) in cats suggesting maintained excitability to the same stimulation. "
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    ABSTRACT: Converging evidence from animal and human studies suggest that rapid eye movement (REM) sleep modulates emotional processing. The aim of the present study was to explore the effects of selective REM sleep deprivation (REM-D) on emotional responses to threatening visual stimuli and their brain correlates using functional magnetic resonance imaging (fMRI). Twenty healthy subjects were randomly assigned to two groups: selective REM-D, by awakening them at each REM sleep onset, or non-rapid eye movement sleep interruptions (NREM-I) as control for potential non-specific effects of awakenings and lack of sleep. In a within-subject design, a visual emotional reactivity task was performed in the scanner before and 24 h after sleep manipulation. Behaviorally, emotional reactivity was enhanced relative to baseline (BL) in the REM deprived group only. In terms of fMRI signal, there was, as expected, an overall decrease in activity in the NREM-I group when subjects performed the task the second time, particularly in regions involved in emotional processing, such as occipital and temporal areas, as well as in the ventrolateral prefrontal cortex, involved in top-down emotion regulation. In contrast, activity in these areas remained the same level or even increased in the REM-D group, compared to their BL level. Taken together, these results suggest that lack of REM sleep in humans is associated with enhanced emotional reactivity, both at behavioral and neural levels, and thus highlight the specific role of REM sleep in regulating the neural substrates for emotional responsiveness.
    Frontiers in Behavioral Neuroscience 06/2012; 6:25. DOI:10.3389/fnbeh.2012.00025 · 3.27 Impact Factor
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    • "Therefore, it is possible that upon REMSD an increased activity in DR neurons will cause increased Na+ concentration inside the neurons. REMSD-induced increased intracellular positivity, a reflection of depolarization of neurons, supports this view [38]. Increased Na+ concentration and metabolites inside a cell would cause increased water influx into the neurons due to osmosis, thus resulting in swelling and increased cell size [4,39]. "
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    ABSTRACT: This study was carried out to investigate the effect of rapid eye movement sleep (REMS) deprivation (REMSD) on the cytomorphology of the dorsal raphe (DR) neurons and to evaluate the possible role of REMSD-induced increased noradrenalin (NA) in mediating such effects. Rats were REMS deprived by the flowerpot method; free moving normal home cage rats, large platform and post REMS-deprived recovered rats were used as controls. Further, to evaluate if the effects were induced by NA, separate sets of experimental rats were treated (i.p.) with α1-adrenoceptor antagonist, prazosin (PRZ). Histomorphometric analysis of DR neurons in stained brain sections were performed in experimental and control rats; neurons in inferior colliculus (IC) served as anatomical control. The mean size of DR neurons was larger in REMSD group compared to controls, whereas, neurons in the recovered group of rats did not significantly differ than those in the control animals. Further, mean cell size in the post-REMSD PRZ-treated animals was comparable to those in the control groups. IC neurons were not affected by REMSD. REMS loss has been reported to impair several physiological, behavioral and cellular processes. The mean size of the DR neurons was larger in the REMS deprived group of rats than those in the control groups; however, in the REMS deprived and prazosin treated rats the size was comparable to the normal rats. These results showed that REMSD induced increase in DR neuronal size was mediated by NA acting on α1-adrenoceptor. The findings suggest that the sizes of DR neurons are sensitive to REMSD, which if not compensated could lead to neurodegeneration and associated disorders including memory loss and Alzheimer's disease.
    Behavioral and Brain Functions 10/2010; 6(1):62. DOI:10.1186/1744-9081-6-62 · 1.97 Impact Factor
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    • "Disturbed or loss of REM sleep is witnessed in several psychosomatic pathological conditions like schizophrenia, epilepsy, mood disorder, memory loss, etc. (Benca, 2001; Monti and Monti, 2005; Walker and Stickgold, 2006; Gottesmann and Gottesmann, 2007) while it is also correlated with an increase in neuronal excitability (Mallick et al., 1989, 1994; Das and Mallick, 2007). It has been shown that Na-K-ATPase directly modulates neuronal transmembrane potential (Trachtenberg et al., 1981; Horisberger et al., 1991). "
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    ABSTRACT: Rapid eye movement (REM) sleep deprivation elevates noradrenaline level, which upon acting on alpha1-adrenoceptors increases Na-K-ATPase activity; however, the detailed intracellular mechanism of action was unknown. Since membrane integrity is crucial for maintaining Na-K-ATPase activity as well as ionic exchange and noradrenaline affects membrane lipid-peroxidation, we proposed that the deprivation might modulate membrane lipid-peroxidation, which would modulate intracellular ionic concentration and thereby increase Na-K-ATPase activity. Hence, in this in vivo and in vitro study, rats were deprived of REM sleep for 4 days by the flowerpot method and suitable control experiments were conducted. The deprivation simultaneously decreased membrane lipid-peroxidation as well as increased Na-K-ATPase activity by its dephosphorylation and all the effects were induced by noradrenaline. Further, in vitro experiments showed that hydrogen peroxide (H(2)O(2))-induced enhanced lipid-peroxidation increased synaptosomal calcium (Ca(2+))-influx, which was also prevented by noradrenaline and nifidipine, an L-type Ca(2+)-channel blocker. Additionally, both nifidipine and cyclopiazonic acid, which have opposite effects on intracellular Ca(2+)-concentration, prevented deprivation induced increased Na-K-ATPase activity. We propose that REM sleep deprivation elevates noradrenaline level in the brain that acting on alpha1-adrenoceptor simultaneously reduces membrane lipid-peroxidation but activates phospholipase-C, resulting in closure of L-type Ca(2+)-channel and releasing membrane bound Ca(2+); the latter then dephosphorylates Na-K-ATPase, the active form, causing its increased activity.
    Neuroscience 06/2008; 155(1):76-89. DOI:10.1016/j.neuroscience.2008.04.069 · 3.36 Impact Factor
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