The study “Uridine treatment prevents REM sleep deprivation- Induced learning and memory impairment” will be discussed. Mice were the subjects in this study. REM deprivation was induced via the flower pot method. After REM deprivation was achieved half the mice were given Uridine. Uridine is known to promote sleep and induces REM. The mice were given a maze with a direct path to the end along with other indirect-routes. The mice with the Uridine treatment tended to complete the maze in a much more efficient manner than the untreated mice. This indicates that REM inducers may improve cognition in sleep deprived subjects.
2. The study “Venlafaxine treatment reduces the deficit of executive control of attention in patients with major depressive disorder” will be discussed. This study focused on patients with major depressive disorder. Venlafaxine was used to study the effects it has on executive control of attention. The study compared 34 patients with major depressive disorder and 30 healthy controls. The subjects were all assessed based on alerting, orientation and executive control. Along with this the scores of the subjects with major depressive disorder were compared pre and post intervention of Venlafaxine. Venlafaxine showed that it significantly decreased the clinical scores of major depressive disorder. Along with this reaction time decreased when patients with MDD that received Venlafaxine. Executive control was also increased post venlafaxine treatment. The mechanisms behind the attentional improvements aren’t fully understood. With Venlafaxine being a common REM inducer, I can speculate that this may play a role in the improvements of attention.
3) The study “Sleep quality of medical students and relationships with academic performances” test medical student knowledge on optimal sleep habits. There were 117 subjects in this study all of which were asked about their sleeping habits, along with exams to test their knowledge on sleep, and exams to see their educational performance. The results indicate that common sleep practices weren’t well known within the sample. The study also indicated that 49.7% of the subjects had poor sleep habits. They also found a correlation between poor sleep and poor academic success.
4) This study uses neural imaging such as electroencephalograms and EEGs in order to determine one of the many mechanisms responsible for memory consolidation during REM. Most of the prior literature had been about oscillations during predominately NREM sleep but this study focused on the REM phase. The results of the paper were interesting as they propose a mechanism that is partially responsible for memory consolidation that hadn’t been previously discussed. The study states that REM sleep is crucial for maintaining neural homeostasis by down regulating the excitability of humans. They state that REM sleep is vital for excitability as it promotes elimination off the synapses which rebalances daytime excessive excitation. The study also states that NREM oscillations are responsible for mediating neuroplasticity by repetitive replay of firing sequences.
5) The study “Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory” looks into the underlying comorbidities and potential causes of PTSD. One of the more interesting things about this study was their discussion on how REM deprivation can slow down or haunt progress in treating PTSD. Since encodement of memories takes place during sleep, the comorbid insomnia may interfere with the extinction of traumatic memories. A common symptom of PTSD is associating everyday sound with sounds similar to the traumatic experiences, this is usually mitigated by presenting the feared stimulus until it’s no longer associated with the fear. This action requires encoding as it's actually a new Emory and by preventing this process progress will be diminished. Along with this they described PTSD and Insominia’s interaction as a positive feedback loop. Essentially saying trauma causes poor sleep and then as a result of the poor sleep more stress is induced, and the cycle continues. This article gave me vast insight to the mechanisms that affect day to day functions of both people suffering with PTSD and those who are not.
6) The study, “Cognitive performance in REM sleep behavior disorder: a possible early marker of neurodegenerative disease?” looks at patients with sleep behavior disorder and looks for links for neurodegenerative diseases. The study looked at twenty three subjects with idiopathic sleep behavior disorder and the subjects underwent a “neurophysiological battery to test multiple cognitive domains”. The results indicate that the subjects performed worse on word span, recall and logical memory tests. In the discussion section the researchers state that the physiological tests performed showed similarities in cognition between people with sleep behavior disorder and Lewwy body disease. This led to the researchers hypothesizing that there is a link between sleep behavior disorder and other neurodegenerative diseases
7) The study, “Neurocognitive Consequences of Sleep Deprivation” Takes a look at the severity of complications that accompany sleep deprivation along with some of the anatomical deficiencies that come with little sleep. One of the interesting findings of this study was that acute sleep deprivation and cognitive consequences accumulate over time and can even reach the level of total sleep deprivation if prolonged. The study indicates that the anterior cingulate and posterior parietal systems are moist predominantly affected by sleep loss. Sleep deprivation drastically alters wake state stability which underlies the cognitive dysfunction that is caused by deprivation. The study indicated that there is a genetic component to the ability to function under sleep deprivation. Researchers are now looking into this genetic component but it is not yet understood.
8) The study, “Sleep deprivation as a neurobiologic and physiologic stressor: allostasis and allostatic load” researches the allostatic load that accompanies sleep deprivation. The allostatic load references the everyday wear and tear that accumulates within the body causing long term health problems. On a hormonal level sleep deprivation causes spikes in cortisol and insulin levels. Poor insulin maintenance can cause a host of problems the main being diabetic, this can have a snowball effect as diabetes is accompanied by a slew of comorbidities. Cortisol levels have such a strong influence on perceived stress levels that cortisol levels have been used as a measurement for stress. Chronic stress is shown to increase the tendency for allostatic overload which is accompanied with atrophy of neurons within the hippocampus and prefrontal cortex. This drastically worsens memory and overall cognitive performance. The conclusions were that lack of sleep increases allostatic load which can have long term consequences in overall health.
9) The study, ”Effects of sleep deprivation on serum cortisol level and mental health in servicemen” Shows the relationship between sleep deprivation and cortisol levels, while simultaneously correlating the results to the state of their mental health. The study was conducted on 207 Chinese service men. 149 of the service men were sleep deprived for 24 hours. Blood tests were taken before and after deprivation to test cortisol levels. Following 24 hours of sleep deprivation showed that cortisol level was significantly higher compared to the control. Following this the service men were given a mental health screening and their results were compared to the mean results of the military. The screenings showed that sleep deprived men performed worse on the cognitive screening which allowed them to correlate cortisol levels with worsened mental health.
10) The study, “High cortisol levels are associated with cognitive impairment no-dementia (CIND) and dementia” compares the cortisol level between three groups of cognitive function. The groups compared were the control, CIND patients and dementia patients. The study consisted of 309 elderly subjects 158 of them were controlled, 92 had CIND, and 59 with dementia. The results of the study showed that dementia patients had the highest cortisol level, followed by patients with CIND. The study suggests a correlation between increased cortisol level and cognitive impairment. The study states that more experiments must be conducted to see if cortisol levels are actually a precursor to these impairments, rather than caused by them.
11) ”Chronic Sleep Deprivation in Mouse Pups by Means of Gentle Handling” details the methods used for their sleep deprivation protocol. The technique they use is called gentle handling. This method is used to cause sleep deprivation while minimizing the anxiety the mouse endures during the procedure. The technique is simple: place the mouse in a small cage with openings. Whenever the mouse shows signs of falling asleep, you gently prod it with a paintbrush. Examples of signs of sleep are inactivity, twitching, or eyes closed.
12)The article, "Sleep Deprivation by the "Flower Pot" Technique and Spatial Reference Memory" describes the methods and results of the flower pot method. The flower pot method entails putting a mouse on a platform roughly the size of its body, which is in a pot filled with water. This method utilizes the body's tendency to lose muscle tone when in REM sleep. This causes the mice to fall off and fall in the water. You place the mouse back on the platform and repeat until the time period is complete. The results indicate a significant decrease in reference memory
13)The article, “Fully automated sleep deprivation in mice as a tool in sleep research” gives a brilliant method for a total sleep deprivation protocol. The mouse is placed into a wheel connected to an electromyography reader on the mouse. Based on the signals read by the electrodes the wheel will spin. If the signals drop this indicates a state of rest, this queues the wheel to spin which wakes up the mouse. This method was shown to be just as effective as the flower-pot method and the gentle handling method, and showed to be less stress inducing than both of those protocols.
14)The article, “Low-grade neuroinflammation due to chronic sleep deprivation results in anxiety and learning and memory impairments” uses the rotating drum method to achieve sleep deprivation. This method entails putting a mouse in a chamber that has a rotating floor; this forces the mouse to continue moving. You keep the mouse in the chamber until the time period ends. The article’s results indicate an upregulation of “protein expression of inflammatory cytokines, transcription factors as well as astroglial and microglial cells.”
15)The design pamphlet, “Mouse Sleep Deprivation Device” describes many ways of performing sleep deprivation protocols. One of the ways is called the sliding bar technique. This method entails a cage with a bar that can be slid across the floor. By constantly sliding the bar, the mice are forced to keep moving, causing total sleep deprivation
16)The article, “Impairment on the hippocampal-dependent virtual Morris water task in schizophrenia” utilizes the Morris water task to study the deficits in spatial memory accompanying schizophrenia. The Morris water task is a test where a mouse is conditioned to swim to a platform that is above water. Then the water level is raised and made murky using non-fat powdered milk or tempera paint. This makes it so the mice have to rely on their spatial memory to find the platform. The study showed that mice with schizophrenia do not use their hippocampus when performing this task. Rather, they rely on allocentric navigational abilities. This reduced their efficiency in finding the platform.
17)The article, “Effects of morphine and its withdrawal on Y-maze spatial recognition memory in mice” investigates the effects of morphine and its withdrawals on spatial memory. In this study they use the Y test, The Y test is performed using a three pronged cage in the shape of a Y. The mice are trained to associate each passageway with food to drive their foraging instincts. Mice tend to not explore the same location twice to improve efficiency of foraging. This allows the researcher to collect data on their spatial memory as subjects that chose the same passageway twice have a decreased social memory. This study concluded that morphine and its withdrawal significantly decreased spatial memory.
18)The article, "Decreased memory for novel object recognition in chronically food-restricted mice is reversed by acute ghrelin administration" uses the novel object recognition test to investigate the effects of ghrelin on retention memory of food deprived mice. The novel object recognition task includes a mouse in a box presented with two objects. The mouse is allowed time to acclimate with these objects until it is taken out. Next, one of the objects is relocated, and the mouse is given time to adjust to that until it's taken out. At this point, you will know if there are any natural aversions to an object and can select the object best suited for the remainder of the trial. The final is the novel object test, where a new object is placed into the box in the same place as one of the prior objects. The longer the time the mouse spends with the novel object, the better their recognition of it being a new object. The results of this test indicate that when food is restricted without treatment of ghrelin, retention memory is significantly decreased. Post-treatment, their retention memory scores increase back to control levels.
19)The study," Effects of NMDA receptor antagonists on passive avoidance learning and retrieval in rats and mice" Uses the passive avoidance learning test to investigate the effects that NMDA agonists have on memory. The passive avoidance test is broader; it entails pairing an aversive stimulus with another to gauge the animal's fear-learning behaviors. The study concluded that subjects who were given the NMDA agonist scored significantly worse on fear memory than the control.
20)The article “Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine, and electroconvulsive shock” uses the plus maze test to evaluate the effects of nootropics, electric shocks, and scopolamine on memory. The plus maze is a test that has two open arms and two enclosed arms. The mice prefer the enclosed space, so they relocate to that arm. The time it takes for them to get from the open arm to the closed area is called the transfer latency. When a second trial is run, you can compare the two transfer latencies to gauge their memory. The electric shocks and scopolamine were shown to decrease their spatial memory along with increased anxiety. In contrast, aniracetam was shown to mitigate the effects of these two drugs.
21)The article “Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine, and electroconvulsive shock” uses the plus maze test to evaluate the effects of nootropics, electric shocks, and scopolamine on memory. The plus maze is a test that has two open arms and two enclosed arms. The mice prefer the enclosed space, so they relocate to that arm. The time it takes for them to get from the open arm to the closed area is called the transfer latency. When a second trial is run, you can compare the two transfer latencies to gauge their memory. The electric shocks and scopolamine were shown to decrease their spatial memory along with increased anxiety. In contrast, aniracetam was shown to mitigate the effects of these two drugs.
22)The article, “Decreased muscarinic binding sites in small intestine from mice treated with neostigmine” This article investigates how neostigmine affects muscarinic binding sites. This has effects on the parasympathetic nervous system. Anti-cholinesterase drugs like neostigmine have a REM-inducing effect. The article describes how it should be administered. The article describes the neostigmine should be dissolved into the mice’s drinking water at 20 to 1000 ppm. This should be done daily.
23)I thought it would be interesting to look at the most common remedy for sleep deprivation and compare the results of it to the REM inducers. This is the supplementation of melatonin. The article "Melatonin ameliorates anxiety-like behaviors induced by sleep deprivation in mice: Role of oxidative stress, neuroinflammation, autophagy, and apoptosis," describes the proper dosing for melatonin along with its effects on stress in sleep-deprived mice. They gave the mice 20-40 mg/kg of melatonin. The results indicate that post-treatment of melatonin showed a significant reduction in plasma cortisol levels; they used this as the measurement to display melatonin's anti-anxiety properties.
24)The article “The acute effects of mirtazapine on pain-related behavior in healthy animals” describes the proper dosage for intravenous mirtazapine along with investigating the mechanisms behind mirtazapine's pain-relieving properties. The article investigates the effects different dosages have on the mice’s pain-related behaviors. For a weak effect, they administered 5 mg/kg; for a medium effect, 10 mg/kg; and for a large effect, 20 mg/kg. The article concluded that mirtazapine doesn’t relieve pain antinociceptive; rather, it is mitigated via serotonergic and opiatergic pathways.
25) I also thought it would be useful to investigate the most common insomnia drug on the market, which is Zolpidem (also known as Ambien). The article "Antiaggressive Effects of Zolpidem And Zopiclone in Agonistic Encounters Between Male Mice" details Zolpidem's effects on aggression in mice while giving information on proper dosing. They gave the mice a dosage of 0.75-3.0 mg/kg of Zolpidem. The study results indicate a significant decrease in aggression for both Zolpidem and zopiclone. Zopiclone only resulted in decreased aggression at dosages higher than 1.5 mg/kg.