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
Source: PubMed


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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    • "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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    • "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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