Noradrenaline acting on alpha1-adrenoceptor mediates REM sleep deprivation-induced increased membrane potential in rat brain synaptosomes.
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.
- [Show abstract] [Hide abstract]
ABSTRACT: Na+,K+-ATPase is a membrane protein which plays a key role in the maintenance of ion homeostasis that is necessary to neuronal excitability, secondary transport and neurotransmitter uptake. Mild hyperhomocysteinemia leads to several clinical manifestations and particularly cerebral diseases; however, little is known about the mechanisms of homocysteine on cerebral Na+,K+-ATPase. In the present study, we investigated the effect of mild hyperhomocysteinemia on the activity, the immunocontent of catalytic subunits (α 1, α 2, and α 3) and the gene expression of this enzyme. We used the experimental model of mild hyperhomocysteinemia that was induced by homocysteine administration (0.03 μmol/g of body weight) twice a day, from the 30th to the 60th postpartum day. Controls received saline in the same volumes. Results showed that mild hyperhomocysteinemia significantly decreased the activity and the immunocontent of the α 1 and α 2 subunits of the Na+,K+-ATPase in cerebral cortex and hippocampus of adult rats. On the other hand, we did not observe any change in levels of Na+,K+-ATPase mRNA transcripts in such cerebral structures of rats after chronic exposure to homocysteine. The present findings support that the homocysteine modulates the Na+,K+-ATPase and this could be associated, at least in part, with the risk to the development of cerebral diseases in individuals with mild hyperhomocysteinemia.Molecular and Cellular Biochemistry 03/2013; · 2.39 Impact Factor
Article: Food addiction and bulimia nervosa[Show abstract] [Hide abstract]
ABSTRACT: In individuals with obesity and binge eating disorder (BED) eating patterns can show addictive qualities, with similarities to substance use disorders (SUDs) on behavioral and neurobiological levels. Bulimia nervosa (BN) has received less attention in this regard, despite their regular binge eating symptoms. The Yale Food Addiction Scale (YFAS) was developed according to the DSM-IV diagnostic criteria for SUDs and food addiction can be diagnosed when at least three addiction symptoms are endorsed and a clinically significant impairment or distress is present. Although the prevalence of food addiction diagnoses is increased in individuals with obesity and BED, recent studies which used the YFAS showed that there are also individuals with normal weight who can be classified as being ‘food addicted’. Based on self-reported eating disorder symptoms, women with current (n = 26) or remitted (n = 20) BN, and a control group of women matched for age and body mass index (n = 63) completed the YFAS and other measures. Results revealed that all patients with current BN received a food addiction diagnosis according to the YFAS while only six (30%) women with remitted BN did. None of the women in the control group received a food addiction diagnosis. Results provide support for the notion that BN can be described as addiction-like eating behavior and suggest that food addiction most likely improves when BN symptoms remit.European Eating Disorders Review 06/2014; 22(5). · 1.38 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Sleep disturbances are prevalent in clinical anxiety but it remains unclear whether they are cause and/or consequence of this condition. Fear conditioning constitutes a valid laboratory model for the acquisition of normal and pathological anxiety. To explore the relationship between disturbed sleep and anxiety in more detail, the present study evaluated the effect of partial sleep deprivation (SD) on fear conditioning in healthy individuals. The neural correlates of (1) non-associative learning and physiological processing, and (2) associative learning (differential fear conditioning) were addressed. Measurements entailed simultaneous functional magnetic resonance imaging (fMRI), electroencephalography (EEG), skin conductance response (SCR) and pulse recordings. Regarding non-associative learning (1), partial SD resulted in a generalized failure to habituate during fear conditioning as evidenced by reduced habituation of SCR and hypothalamus responses to all stimuli. Furthermore, SCR and hypothalamus activity were correlated, supporting their functional relationship. Regarding associative learning (2) effects of partial SD on the acquisition of conditioned fear were weaker and did not reach statistical significance. The hypothalamus plays an integral role in the regulation of sleep and autonomic arousal. Thus, sleep disturbances may play a causal role in the development of normal and, possibly, pathological fear by increasing the susceptibility of the sympathetic nervous system to stressful experiences.Journal of Neurophysiology 06/2014; · 3.04 Impact Factor