Serotonin, Sleep and Depression: A Hypothesis

For most cases of endogenous depression (major depression), the hypothesis of monoamine deficiency, despite a number of limitations it faces, is still considered the most acceptable explanation. The main difficulty faced by this hypothesis is the reason for the decrease in the level of cerebral monoamines (primarily serotonin) during depression. It is assumed either increased activity of the MAO enzyme, which metabolizes serotonin, or a mutation with the loss of function of the gene of the Tph-2 enzyme, which synthesizes serotonin, as possible causes. In this review, a third cause is proposed, which can explain a number of cases of «spontaneous» onset of depressive symptoms in apparently healthy people, as well as links the hypotheses of “monoamine deficiency” and “disturbances in circadian rhythms.” It is assumed that the formation of endogenous depression is due to a combination of two factors: a reduced “basal” level of cerebral serotonin and excessively long pre-morning periods of REM sleep, during which the release of cerebral monoamines stops altogether. As a possible way to of non-drug treatment of depression, not deprivation, but fragmentation of this phase of sleep is suggested, that is much easier for patients to tolerate

THE PEPTIDERGIC MODULATION OF SLEEP

A close interconnection between the systems of sleep and stresses has been detected, which is realized through some brain peptides: peptide of delta-sleep, muramil-peptide and etc.; the synthetic analogs of the delta-sleep peptide, possessing the high resistance to the aminopeptidases, can render significant effects on sleep. The design on creation of the new medicinal preparations of the sleeping draught and stress-protective action have realized; the original automatic analyzer of sleep is being developed for the clinic applicationAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

Hippocampus-dependent and Associative Memory in Mice Subjected to Acute Predator Stress

Proceedings of the 9th International Multidisciplinary Conference «Stress and Behavior» Saint-Petersburg, Russia, 16–19 May 2005.A number of studies documented contradictory effects of acute stress on learning abilities. Here, we investigated effects of predator stress in mice on two distinct types of memory: a hippocampus-dependent contextual memory and a cortex-dependent conditioned taste aversion associative learning. Also, we related memory scores to individual copying strategies of social behavior. Employed stress paradigm was proposed earlier as a model of extreme environmental stress in humans.Methods. Male CD1 mice have been tested in a resident-intruder paradigm, in which animals display either dominant or subdominant types of social behavior. Type of social behavior in mice is considered to be a valuable parameter reflecting stress-responsiveness and general style of behavioral coping with various aversive situations. Two month after testing, animals were exposed to predator stress for a time period of 9 h. Therefore they were placed into a small container and introduced to a cage, which was containing a rat; mice were water and food deprived during entire period of stress. Non-stressed animals remained untreated and were kept in regular animal facility. 4 hours after termination of stress, stressed and non-stressed animals were split to two experimental groups and trained in two learning tasks. Half of animals were subjected to a conditioned taste aversion paradigm. Animals were previously trained to a special water drinking schedule, getting a 2-h access to water daily. For training, they received 2.5 % sucrose solution and 30 min later were injected with 0.18 M/kg LiCl that caused nausea in all mice. 24 h later, mice were tested for their preference to sucrose solution (a parameter of associative memory), in a two-bottle paradigm based on a choice between sucrose solution and plain water. Second half of stressed and control animals was trained in a step-down avoidance paradigm. Mice learned to refrain from stepping down onto a grid floor in order to avoid an electric shock. In this test, baseline latency of stepping down, a measure of anxiety-related behavior, as well as short-term and long-term memory was estimated.Results and discussion. Among control mice subjected to training in conditioned taste aversion paradigm, six out of nine animals showed decreased preference to sucrose (below 50 %) as compared to mice not treated with LiCl (mean preference to sucrose 90 %) and were considered as good learners. In the stress group, five out of ten animals acquired conditioned taste aversion task. The only difference between the groups was in water drinking: stressed mice showed reduced water consumption. Thus, predator stress does not impair associative learning in conditioned taste aversion paradigm. In a step-down avoidance paradigm, stressed mice showed normal learning scores both for short-term memory (during recall session 3 h after training) and long-term memory (during recall session 24 h after training). However, analysis of good learners from the stress group showed that 80 % of them were constituted from mice with subdominant type of behavior. Notably, preliminary experiments in naпve mice did not reveal any differences in acquisition of step-down avoidance between dominant and subdominant groups of mice. In a present experiment, parameters of anxiety were not statistically different between the groups; moreover, dominant mice had a tendency to have higher anxiety scores. These data suggest that differences in learning of passive avoidance task between dominant and subdominant mice cannot be explained by unspecific changes in anxiety-related behavior.Conclusion. Thus, the type of behavioral copying plays a significant role in stress-responsiveness and hippocampus-dependent learning in male mice subjected to acute stress

Sleep-wakefulness cycle and behavior in pannexin1 knockout mice

•Waking is increased and slow wave sleep is decreased in the dark period in mice deficient for Panx1.•Movement activity is increased throughout the light/dark cycle in mice deficient for Panx1.•The lack of pannexin modifies animal behavior in vertical and horizontal pole tests. Pannexins are membrane channel proteins that play a role in a number of critical biological processes (Panchin et al., 2000; Shestopalov, Panchin, 2008). Among other cellular functions, pannexin hemichannels serve as purine nucleoside conduits providing ATP efflux into the extracellular space (Dahl, 2015), where it is rapidly degraded to adenosine. Pannexin1 (Panx1) is abundantly expressed in the brain and has been shown to contribute to adenosine signaling in nervous system tissues (Prochnow et al., 2012). We hypothesized that pannexin1 may contribute to sleep-wake cycle regulation through extracellular adenosine, a well-established paracrine factor in slow wave sleep. To investigate this link, EEG and movement activity throughout the light/dark cycle were compared in Panx1−/− and Panx1+/+ mice. We found a significant increase in waking and a correspondent decrease in slow wave sleep percentages in the Panx1−/− animals. These changes were especially pronounced during the dark period. Furthermore, we found a significant increase in movement activity of Panx1−/− mice. These findings are consistent with the hypothesis that extracellular adenosine is relatively depleted in Panx1−/− animals due to the absence of the ATP-permeable hemichannels. At the same time, sleep rebound after a 6-h sleep deprivation remained unchanged in Panx1−/− mice as compared to the control animals. Behavioral tests revealed that Panx1−/− mice were significantly faster during their descent along the vertical pole but more sluggish during their run through the horizontal pole as compared to the control mice

Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle

During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1 −/− mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx) in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Panx in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle

Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle

During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1−/− mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx) in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Panx in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle