GLUT4, GLUT1, and GLUT8 are the dominant GLUT transcripts expressed in the murine left ventricle

BACKGROUND: The heart derives energy from a wide variety of substrates including fatty acids, carbohydrates, ketones, and amino acids. The healthy heart generates up to 30% of its ATP from glucose. Under conditions of cardiac injury or stress, the heart relies even more heavily on glucose as a source of fuel. Glucose is transported into the heart by members of the family of facilitative glucose transporters (GLUTs). While research examining the transport of glucose into the heart has primarily focused on the roles of the classical glucose transporters GLUT1 and GLUT4, little is known about the functions of more newly identified GLUT isoforms in the myocardium. METHODS: In this study the presence and relative RNA message abundance of each of the known GLUT isoforms was determined in left ventricular tissue from two commonly used inbred laboratory mouse strains (C57BL/6J and FVB/NJ) by quantitative real time PCR. Relative message abundance was also determined in GLUT4 null mice and in murine models of dilated and hypertrophic cardiomyopathy. RESULTS: GLUT4, GLUT1, and GLUT8 were found to be the most abundant GLUT transcripts in the normal heart, while GLUT3, GLUT10, and GLUT12 are present at relatively lower levels. Assessment of relative GLUT expression in left ventricular myocardium from mice with dilated cardiomyopathy revealed increased expression of GLUT1 with reduced levels of GLUT4, GLUT8, and GLUT12. Compensatory increase in the expression of GLUT12 was observed in genetically altered mice lacking GLUT4. CONCLUSIONS: Glucose transporter expression varies significantly among murine models of cardiac dysfunction and involves several of the class III GLUT isoforms. Understanding how these more newly identified GLUT isoforms contribute to regulating myocardial glucose transport will enhance our comprehension of the normal physiology and pathophysiology of the heart

CPEB3 is Associated with Human Episodic Memory

Cytoplasmic polyadenylation element-binding (CPEB) proteins are crucial for synaptic plasticity and memory in model organisms. A highly conserved, mammalian-specific short intronic sequence within CPEB3 has been identified as a ribozyme with self-cleavage properties. In humans, the ribozyme sequence is polymorphic and harbors a single nucleotide polymorphism that influences cleavage activity of the ribozyme. Here we show that this variation is related to performance in an episodic memory task and that the effect of the variation depends on the emotional valence of the presented material. Our data suggest a role for human CPEB3 in human episodic memory

Preventive effect of beta-adrenoceptor blockade on glucocorticoid-induced memory retrieval deficits

Elevated glucocorticoid levels impair retrieval of emotional information, and animal studies indicate that this effect depends on concurrent emotional arousal-induced increases in noradrenergic transmission within the brain. The authors investigated whether the beta-adrenoceptor antagonist propranolol blocks glucocorticoid-induced memory retrieval impairments in human subjects.; In a double-blind, placebo-controlled study, 42 healthy volunteers were presented a set of words with variable emotionality and asked to learn them for recall. A day later, cortisone (25 mg), propranolol (40 mg), or both drugs were administered orally 1 hour before a free-recall test.; Cortisone selectively impaired the recall of emotionally arousing words by 42%. This impairment was blocked by the concurrent administration of propranolol. Propranolol alone did not affect recall of either emotional or neutral words.; A pharmacological blockade of beta-adrenoceptors prevents glucocorticoid-induced memory retrieval deficits in human subjects. This finding may have important implications for the treatment of memory deficits in hypercortisolemic states, such as stress and depression

GLUT4, GLUT1, and GLUT8 are the dominant GLUT transcripts expressed in the murine left ventricle

Abstract Background The heart derives energy from a wide variety of substrates including fatty acids, carbohydrates, ketones, and amino acids. The healthy heart generates up to 30% of its ATP from glucose. Under conditions of cardiac injury or stress, the heart relies even more heavily on glucose as a source of fuel. Glucose is transported into the heart by members of the family of facilitative glucose transporters (GLUTs). While research examining the transport of glucose into the heart has primarily focused on the roles of the classical glucose transporters GLUT1 and GLUT4, little is known about the functions of more newly identified GLUT isoforms in the myocardium. Methods In this study the presence and relative RNA message abundance of each of the known GLUT isoforms was determined in left ventricular tissue from two commonly used inbred laboratory mouse strains (C57BL/6J and FVB/NJ) by quantitative real time PCR. Relative message abundance was also determined in GLUT4 null mice and in murine models of dilated and hypertrophic cardiomyopathy. Results GLUT4, GLUT1, and GLUT8 were found to be the most abundant GLUT transcripts in the normal heart, while GLUT3, GLUT10, and GLUT12 are present at relatively lower levels. Assessment of relative GLUT expression in left ventricular myocardium from mice with dilated cardiomyopathy revealed increased expression of GLUT1 with reduced levels of GLUT4, GLUT8, and GLUT12. Compensatory increase in the expression of GLUT12 was observed in genetically altered mice lacking GLUT4. Conclusions Glucose transporter expression varies significantly among murine models of cardiac dysfunction and involves several of the class III GLUT isoforms. Understanding how these more newly identified GLUT isoforms contribute to regulating myocardial glucose transport will enhance our comprehension of the normal physiology and pathophysiology of the heart.</p

Glucocorticoids reduce phobic fear in humans

Phobias are characterized by excessive fear, cued by the presence or anticipation of a fearful situation. Whereas it is well established that glucocorticoids are released in fearful situations, it is not known whether these hormones, in turn, modulate perceived fear. As extensive evidence indicates that elevated glucocorticoid levels impair the retrieval of emotionally arousing information, they might also inhibit retrieval of fear memory associated with phobia and, thereby, reduce phobic fear. Here, we investigated whether acutely administrated glucocorticoids reduced phobic fear in two double-blind, placebo-controlled studies in 40 subjects with social phobia and 20 subjects with spider phobia. In the social phobia study, cortisone (25 mg) administered orally 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation, exposure, and recovery phase of the stressor. Moreover, the stress-induced release of cortisol in placebo-treated subjects correlated negatively with fear ratings, suggesting that endogenously released cortisol in the context of a phobic situation buffers fear symptoms. In the spider phobia study, repeated oral administration of cortisol (10 mg), but not placebo, 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again 2 days after the last cortisol administration, suggesting that cortisol may also have facilitated the extinction of phobic fear. Cortisol treatment did not reduce general, phobia-unrelated anxiety. In conclusion, the present findings in two distinct types of phobias indicate that glucocorticoid administration reduces phobic fear

Low-dose cortisol for symptoms of posttraumatic stress disorder

OBJECTIVE: Because elevated cortisol levels inhibit memory retrieval in healthy human subjects, the present study investigated whether cortisol administration might also reduce excessive retrieval of traumatic memories and related symptoms in patients with chronic posttraumatic stress disorder (PTSD). METHOD: During a 3-month observation period, low-dose cortisol (10 mg/day) was administered orally for 1 month to three patients with chronic PTSD in a double-blind, placebo-controlled, crossover design. RESULTS: In each patient investigated, there was a significant treatment effect, with cortisol-related reductions of at least 38% in one of the daily rated symptoms of traumatic memories, as assessed by self-administered rating scales. In accordance, Clinician-Administered PTSD Scale ratings assessed after each month showed cortisol-related improvements for reexperiencing symptoms and, additionally, in one patient for avoidance symptoms. CONCLUSIONS: The results of this pilot study indicate that low-dose cortisol treatment reduces the cardinal symptoms of PTSD

The Swiss Corona Stress Study: second pandemic wave, November 2020

The results of the third survey of the Swiss Corona Stress Study refer to the period from November 11-19, 2020, during which 11,612 people from all over Switzerland participated. Stress levels have increased significantly compared to the first survey during lockdown in April 2020. While the proportion of people reporting maximum stress levels was around 11% during the April lockdown, it rose to 20% in the second pandemic wave in November. The increase in stress was accompanied by an increase in depressive symptoms. The main drivers of psychological stress and depressive symptoms included burden due to a Covid-19-related change in work, school, or education, Covid-19-related financial losses, and fears about the future. These stressors have increased significantly, compared to the time of the April lockdown. Further factors were the fear that someone in the closest circle would become seriously ill or die from COVID-19, as well as the burden of social restrictions and burden from an increase in conflicts at home. While the proportion of respondents with moderately severe or severe (PHQ-9 ≥15) depressive symptoms was 3% before the pandemic, 9% during the April lockdown, and 12% during May, it increased to 18% in November. The risk for moderately severe or severe depressive symptoms was associated with age (with younger people showing the highest risk) and was increased in people experiencing financial losses due to the pandemic. In addition, people from the French-speaking part of Switzerland, which was most affected by the pandemic during the second wave, were at higher risk than people from the rest of Switzerland

The Swiss Corona Stress Study

The mental consequences of the COVID-19 pandemic and the strict lockdown measures implemented by governments world-wide to fight it are currently unknown. We performed an online survey study in Switzerland and analyzed data acquired during confinement (wave 1) and during partial lifting of measures (partial deconfinement) (wave 2). Wave 1: Data from over 10’000 individuals living in Switzerland were collected between April 6 and 8, 2020, starting 3 weeks after the beginning of confinement. While 24.4% of the participants reported no change in stress levels, 49.6% of the participants reported an increase in stress levels during confinement as compared to the time before the COVID-19 pandemic. We identified several potential sources for people feeling more stressed during confinement, such as the burden related to changes at work or school, problems with childcare or not being able to spend more time with others. The changes in stress levels were highly correlated with changes in depressive symptoms. 57% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) increased from 3.4% before the COVID-19 pandemic to 9.1% during confinement. Interestingly, 26% of participants showed a decrease in stress level during confinement, suggesting that for those individuals the confinement involved a reduction of stressors and/or resulted in more time for recovery. Finally, we identified several behaviors amenable to change that were related to a reduced increase in stress level and depressive symptoms during confinement. Wave 2: Data from over 10’000 individuals living in Switzerland were collected between May 11 and June 1, 2020 during partial deconfinement. As for wave 1, we observed diverse reactions with regard to stress levels: While 28% of the participants reported no change in stress levels, 40% of the participants reported an increase in stress levels during partial deconfinement as compared to the time before the COVID-19 pandemic. We identified similar sources for people feeling more stressed as during confinement and the changes in stress levels were highly correlated with changes in depressive symptoms. 49.5% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) remained elevated with a prevalence rate of 11.7%. With regard to changeable behaviors during the pandemic, we found (as in wave 1) that spending more time pursuing new projects, spending more time pursuing hobbies at home, and light physical exercise were related to less stress increase. A comparison between the two waves indicated that while the waves did not substantially differ in the distributions of changes in stress levels or depressive symptoms, they did differ with regard to the distribution of anxiety ratings. Specifically, anxiety levels decreased from wave 1 to wave 2. Finally, we identified risk and resilience factors with regard to the development of depressive symptoms (present in both waves): A history of a prior psychiatric disorder was a risk factor for developing moderately severe or severe depressive symptoms during the pandemic. In a resilient group of people who had none or only minimal depressive symptoms before and during the pandemic, older people (≥ 55 years), men and individuals with no history of prior psychiatric disorder were overrepresented. Thus, advanced age, male gender and the absence of prior psychiatric disorder were identified as resilience factors

A functional genetic variation of the 5-HT2a receptor affects human memory

Human memory capacity is highly variable across individuals and is influenced by both genetic and environmental factors. A roughly 50% heritability estimate indicates that naturally occurring genetic variations have an important impact on this cognitive ability. Therefore, we investigated a functional variation of a memory-related serotonin receptor in 349 healthy young volunteers, and found 21% poorer memory performance in subjects with the rare variant