Perceived Stress and Cfognition Function Quantification in a Scary Video Game: An Electroencephalogram Features and Biochemical Measures.

Introduction: Video games affect the stress system and cognitive abilities in different ways. Here, we evaluated electrophysiological and biochemical indicators of stress and assessed their effects on cognition and behavioral indexes after playing a scary video game. Methods: Thirty volunteers were recruited into two groups as control and experimental. The saliva and blood samples were collected before and after intervention (watching/playing the scary game for control and experimental groups respectively). To measure cortisol and salivary alpha-amylase (sAA) levels, oxytocin (OT), and brain-derived neurotrophic factor (BDNF) plasma levels, dedicated ELISA kits were used. Electroencephalography recording was done before and after interventions for electroencephalogram (EEG)-based emotion and stress recognition. Then, the feature extraction (for mental stress, arousal, and valence) was done. Matrix laboratory (MATLAB) software, version 7.0.1 was used for processing EEG-acquired data. The repeated measures were applied to determine the intragroup significance level of difference. Results: Scary gameplay increases mental stress (P<0.001) and arousal (P<0.001) features and decreases the valence (P<0.001) one. The salivary cortisol and alpha-amylase levels were significantly higher after the gameplay (P<0.001 for both). OT and BDNF plasma levels decreased after playing the scary game (P<0.05 for both). Conclusion: We conclude that perceived stress considerably elevates among players of scary video games, which adversely affects the emotional and cognitive capabilities, possibly via the strength of synaptic connections, and dendritic thorn construction of the brain neurons among players. Highlights: The mental stress level increases in players of scary video games.The salivary cortisol and alpha-amylase levels are significantly higher after the scary gameplay.Plasma levels of oxytocin and brain-derived neurotrophic factor decrease after the scary gameplay.The arousal and valence features increase in players of scary video game.Cognitive capabilities are adversely affected by the scary gameplay. Plain Language Summary: Nowadays, video games have become an important part of human life at different ages. Therefore, assessing their effects (improving and/or damaging) on cognition and behavior is important for understanding how they affect the nervous system. The results of such studies can be used to design a variety of games in the future in a way that minimizes the harmful side effects of video games on human cognitive functions and maximizes their beneficial effects.

Protective effects of L-arginine on Alzheimer's disease: Modulating hippocampal nitric oxide levels and memory deficits in aluminum chloride-induced rat model.

There is evidence that high daily intake of aluminum (Al) is associated with an increased risk of dementia or cognitive decline. We injected L-arginine into the dorsal hippocampus (DH) of an AlCl3-induced Alzheimer's model and studied memory deficit, ß-amyloid (ßA) accumulation, neurodegeneration, and molecular changes. Male Wistar rats were cannulated unilaterally in the DH under a stereotaxic apparatus and a dose of AlCl3 (1-200 µg/rat) was injected into the CA1. After recovery, L-arginine and L-NAME (0.05-25 µg/rat) were injected into CA1 and animals were tested in novelty seeking task. One group received ßA (2 µg/rat, intra CA1) as a reference group. Control groups received saline (1 µL/rat, intra-CA1) and galantamine (25 µg/rat, intra-CA1), respectively. Finally, rats were anesthetized and hippocampal tissues were isolated on ice. Levels of neuronal NO synthase (nNOS), ß-secretase and soluble guanylyl cyclase (sGC) were measured by western blotting. ßA formation and the number of CA1 neurons were assessed by Congo red and Nissl staining. NOS activation by NADPH-diaphorase (NADPH-d) was investigated. All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. Like ßA, AlCl3 (25 µg/rat) caused accumulation of ßA in the DH and increased stopping of the animal on the novel side (indicating a recall deficit). CA1 neurons decreased, and nNOS and ß-secretase, but not sGC, showed a change consistent with Alzheimer's. However, prophylactic intervention of L-arginine at 3-9 µg/rat was protective, probably by nNOS stimulation in DH, as shown by NADPH-d assay. L-arginine may protect against Alzheimer's by increasing hippocampal NO levels.

Amelioration of pain and anxiety in sleep-deprived rats by intra-amygdala injection of cinnamaldehyde.

Background: Sleep disorders are accompanied by increased anxiety and somatic pain. In addition, it has been observed that anxiety and pain have a boosting effect on each other, resulting in continued sleep disturbances. Amygdala's (CeA) central nucleus plays a crucial role in these processes. Cinnamaldehyde (Cinn) is an aromatic compound with anti-anxiety, antioxidant, and sleep-promoting properties. The present study uses sleep-deprived rats to examine the effects of an intra-CeA injection of Cinn on pain and anxiety. Methods: Sleep deprivation (SD) was induced using the platform technique. 35 male Wistar rats were divided into five groups. Anxiety state and nociception were evaluated among groups using formalin test (F.T.), open field test (OFT), and elevated plus maze (EPM). Anxiety tests (OFT and EPM) were conducted in all groups. The first group was undergone FT without induction of SD (SD-FT+). The second group received SD without FT(SD+FT-). The third group received both SD and FT(SD+FT+). The treatment and vehicle groups have undergone both SD and FT in addition to the respectively intra-CeA injection of Cinn (SD+FT+ Cinn) and Cinn vehicle (SD+FT+ VC). The recorded behaviors were analyzed between groups using IBM SPSS 24th version. Results: SD did not lead to any significant difference in nociceptive behaviors in FT between groups SD-FT+ and SD+FT+ (P ≥ 0.05). At the same time, there was a considerable discrepancy in rearing behaviors (P < 0.006) and the number of fecal boli (P < 0.004) recorded in OFM between these groups. Treatment with Cinn led to decreased nociception (P < 0.038), decreased rearing behaviors (P < 0.01), and reduced defecation (P < 0.004) in group SD + FT+ Cinn in comparison to the group SD+FT+. There were no differences in anxiety test results between the first and second groups (P ≥ 0.05). Conclusion: SD can lead to elevated anxiety, while intra-CeA injection of Cinn ameliorated both perceptions of acute pain and anxiety. Besides, the conduction of FT before the anxiety test led to no disturbance in the results of anxiety tests.

Effect of Papaver rhoeas hydroalcoholic extract on blood corticosterone and psychosocial behaviors in the mice model of predator exposure-induced post-traumatic stress disorder.

The function of hypothalamic-pituitary-adrenal (HPA) axis and psychosocial behaviors are affected in post-traumatic stress disorder (PTSD). Based on presence of several beneficial alkaloids in Papaver rhoeas (PR) plant, we assessed the effects of PR hydroalcoholic extract on blood corticosterone and psychosocial behaviors in the mice model of predator exposure-induced PTSD. Male NMARI mice were assigned into two main groups (control or PTSD) according to stress exposure (presence or absent of the predator). Each main group was divided into four subgroups according to treatment with the different doses of PR extract. Mice were treated intraperitoneally by PR extract at three different doses (1,5&10 mg/kg) 30 min before the beginning of test on days 1, 2&3. Corticosterone concentration determined in the blood samples on days 1, 3&21, and mice examined for the psychosocial behaviors on the third day. PTSD induction in mice by exposing to hungry predator increased blood corticosterone and changed the psychosocial and physiological behaviors. PR extract decreased blood corticosterone in PTSD mice on the third day as well as 21st day. Also, PR extract improved the psychosocial and physiological behaviors in PTSD mice. Moreover, PR extract increased blood corticosterone in control mice at a dose-response manner. PR extract is able to decrease blood corticosterone in PTSD condition and probably prevent the HPA hyperactivity in PTSD mice when exposed to the stress stimuli. Accordingly, decreased blood corticosterone by PR extract might be involved in improvement of the physiological and psychosocial behaviors in PTSD mice.

Changes in psychological and cognitive variables as well as cortisol levels in recovered Covid-19 patients: a longitudinal study.

BACKGROUND: Decreased psychological and cognitive functioning is one of the complications of Covid-19 disease. We aimed to evaluate mental health, cognitive functioning, and salivary cortisol levels in Covid-19 patients with different disease severities in three 45-day intervals after recovery. METHODS: 258 Covid-19 patients were assigned into three groups based on their disease severity: 112 patients in mild group, 67 patients in moderate group and 79 patients in severe group. The participants underwent psychological evaluations (including Depression, Anxiety and Stress Scale questionnaire, Beck Depression Inventory, SpeilBerger State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Inventory), cognitive assessments (The Paced Auditory Serial Addition Test) and salivary cortisol level evaluation in three 45-day periods. Non-parametric statistical methods were applied for psychological and cognitive indicators, while two-way mixed model ANOVA was used to evaluate the cortisol concentration in three replications. RESULTS: The group of mild patients became more anxious and the group of moderate patients became more anxious and depressed. But all three groups of patients developed severe sleep disorders over time. For cognitive functioning, although the results showed a decrease in the correct response rate, a significant increase in the correct response rate was observed in all three groups in all three measurements. However, the response speed not only did not increase, but also decreased in severe group. Cortisol level had a markedly increasing trend in all three groups. CONCLUSION: Improvement of cognitive functioning was in line with the increase in cortisol. Besides, the decrease in mental health had no effect on the cognitive functioning.

The Effect of Electrical Fields From High-voltage Transmission Line on Cognitive, Biological, and Anatomical Changes in Male Rhesus macaque Monkeys Using MRI: A Case Report Study.

Introduction: Living near high-voltage power lines and exposure to high-frequency electromagnetic fields (EMFs) is a potentially serious hazard to animal and human health. The present study was conducted to evaluate the effect of high-frequency EMFs from simulated high-voltage electric towers on cognitive, anatomical, and biological changes in the male macaque. Methods: In this study, two Rhesus macaque were recruited, one experimental and one control. The experimental subject was exposed to EMFs from 3 kV/m simulated electric towers with a specific protocol and the control subject was tested without irradiation (4h per day, for 30 days). All required tests were performed before and after the intervention on experimental and control monkeys. The anatomical alternation of the prefrontal area (PFA) was measured by MRI images. All tests were performed on irradiated and control animals before and after the intervention and the results were compared between irradiated and control animals. Results: The results of the present study indicated increased white blood cell counts after high-frequency EMFs irradiation. Also, the red blood cell counts showed a decreasing trend after irradiation. The plasma adrenaline level increased after irradiation. Besides, the blood glucose levels increased after irradiation. The PFA was different before and after the irradiation. Moreover, some behavioral disorders, such as fatigue, drowsiness, anorexia, and insomnia were observed after irradiation. Conclusion: The results of biological tests and MRI showed an elevated risk of immunodeficiency disorders, weakness, and behavioral disorders. People who live or work near high-voltage electric towers with high-frequency EMFs are warned. Highlights: Magnetic, and electric fields from high pressure towers caused negative effects in terms of biology and even anatomical changes in the prefrontal part of the brain.Disturbance in the prefrontal part of the brain caused the monkey's cognitive and behavioral disorder.An increase in white blood cells, a decrease in red blood cells, and an increase in the adrenaline and blood sugar were indicative of biological disorders after wave exposure in male rhesus monkeys.The effects of magnetic and electric fields resulting from high pressure towers on the nerves and psyche require health researchers to do more studies. Plain Language Summary: Today, one of the factors that threaten the cognitive and behavioral health of humans and animals is living in the vicinity of magnetic and electric fields resulting from the power transmission of high-pressure towers. These fields cause cognitive and behavioral disorders in living beings. Therefore, because it threatens the cognitive health of creatures, it needs more research.

Prenatal Stress-induced Spatial Memory Deficit in a Sex-specific Manner in Mice: A Possible Involvement of Hippocampal Insulin Resistance.

Introduction: In the present study, the effects of prenatal stress on spatial learning and memory deficit and its relationship with hippocampal insulin resistance were examined in male and female offspring. Methods: Female NMRI mice were mated with males overnight, and the 0-day of pregnancy was detected (Gestational day 0-GD0). The pregnant mice were then randomly divided into stress and control groups. The stress group received stress from the GD0 to GD10. On post natal day 30 (PND30), the offspring were divided into 4 subgroups, namely: male-control, female-control, male-stress, and female-stress. Barnes maze method was used for spatial learning evaluation. Plasma cortisol and insulin levels were measured at the beginning of the experiments. At the end of the experiments, the animals' brains were removed, and their hippocampus was extracted. The hippocampus was homogenized, and its insulin and insulin-receptor contents were evaluated. Results: The stressed animals needed more time for reaching to target hole. In addition, they spend more distance to find the target hole, which was more pronounced in the male offspring. Both plasma and hippocampal insulin content were reduced in the stressed groups. Moreover, the hippocampal insulin receptors protein was reduced in the stressed animals. There was a positive relationship between plasma and hippocampal content and memory deficit in the stressed groups. Conclusion: These results indicated that prenatal stress could induce spatial learning and memory deficit in offspring, which is associated with plasma and hippocampal insulin and receptor content reduction (hippocampal insulin resistance) in these animals. Highlights: Maternal stress is very harmful for fetus.The effect of stress is significant during the early days of gestation.This effect is due to several hormonal and neuronal disturbances including Insulin resistance.The effects of stress on the fetus is gender dependent. Plain Language Summary: The possible effectiveness of prenatal stress on learning and memory in neonates and also the changes in hippocampus as of essential part of the brain involved in learning and memory. We found that prenatal stress can reduce the insulin effects in hippocampus and it may be the main cause of stress on neonatal memory deficits.

Adrenal histological and functional changes after hepatic encephalopathy: From mice model to an integrative bioinformatics analysis.

Hepatic encephalopathy (HE), which is caused by neurotoxin agents in the liver, is a complicated condition with a variety of neurological manifestations. Recently, endocrine alterations have been more paid attention to for neurological severity in the course of HE, e.g. adrenal gland. To identify the role of adrenal gland in the context of HE, we evaluated the functional changes of adrenal gland (i.e., plasma corticosterone concentrations and histopathological changes) in mice model of HE. To dig deep into the molecular and genetic underpinnings, a comprehensive enrichment analysis for shared genes between HE and adrenal insufficiency (AI) was also performed. Our results showed a significant reduction in the level of plasma corticosterone and severe cellular necrosis in zona fasciculate of adrenal cortex, possibly indicating adrenal insufficiency. Enrichment analysis indicated four common genes, besides predicted five novel genes and some significant MicroRNAs (miRNAs) and transcription factors for both HE and AI. Couples with, several biological processes, such as DNA damage, inflammatory responses, glycolytic processes, and insulin receptor signaling pathway were predicted in both HE and AI. To sum up, data from experimental tests and bioinformatics analyses suggest that AI play an important role in the pathogenesis and progression of HE.

Interaction effects of intracerebroventricular injection of crocin with the α2-adrenoceptors on memory deficit and hippocampal synaptic plasticity following chronic pain in rat.

Patients with chronic pain exhibit anxiety and deficits in memory. Additionally, α2-adrenoceptors that are wildly expressed in the brain have an important role in modulating both pain and memory formation. In the present study, we investigated the interaction effects of crocin with central α2-adrenoceptors on pain comorbidity and hippocampal synaptic plasticity changes following chronic constriction injury (CCI) of the sciatic nerve in rats. All the drugs (crocin, an antagonist (yohimbine) and agonist (clonidine) of α2-adrenergic receptors) were injected (via intracerebroventricular injection) from the day of CCI operation (day 0) and continued daily (once per day) until the 14th day post-CCI. The effects of drugs on the cold allodynia (using acetone test) and anxiety-like behaviors (using elevated plus maze, EPM and open field tests) were assessed. Spatial memory (using Barnes maze) was assessed on day 14 post-CCI operation. Hippocampal synaptic plasticity (using in-vivo extracellular field potential recording) was performed on day 14 post-CCI operation. We observed that crocin induced analgesic, anxiolytic and memory enhancer action following CCI surgery. Furthermore, crocin significantly increased long-term potentiation (LTP) (increased fEPSP slope and population spike amplitude). Furthermore, the co-injection of yohimbine effectively decreased analgesic, anxiolytic and enhancer action of crocin on the LTP parameters (fEPSP slope and population spike amplitude). Our study provided information that protective effects of crocin on pain/anxiety responses and synaptic plasticity were possibly mediated by central α2-adrenoceptor in the rats with chronic pain.

The Relationship between the Severity of the COVID-19 Disease, Temperament and Psychological Factors.

Objective: The coronavirus (COVID-19) pandemic negatively affects public mental health around the world. Individuals' reactions to COVID-19 vary depending on their temperament, individual differences, and personality traits. Therefore, the current study is conducted to assess the association of demographical features, Persian temperament, and psychological characteristics with the severity of COVID-19. Method: An online survey was sent to COVID-19 patients to collect their demographic information, COVID-19 symptoms, and clinical data. The Depression, Anxiety and Stress Scale (DAAS-21) questionnaire, Beck Depression Inventory (BDI-II), Spiel Berger State-Trait Anxiety Inventory (STAI) , Pittsburgh Sleep Quality Inventory (PSQI), and Persian general and brain temperament Questionnaire were also completed by 258 participants (127 men and 131 women) 45 days after recovery from COVID-19. Non-parametric analysis was used for statistical analysis. Results: Results showed the significant relationship of demographic factors such as weight, age and gender with the severity of the COVID-19 (P < 0.05). Mean scores of brain temperament (warm/cold) in the severe group were significantly lower than the moderate and mild groups (P < 0.05). There was a significant increase in the dry/wet temperament of the brain in the severe and moderate groups compared to the mild group (P < 0.05). The results of DASS-21 showed a significantly higher anxiety in patients with severe COVID-19 compared with moderate and mild groups (P < 0.05). The severe group was found to be significantly different compared to moderate group in the results of BDI-II (P < 0.05). The result of STAI (state and trait) showed a significant difference between the severe group and the mild and moderate groups. The score of PSQI between the moderate and mild groups was significant (P < 0.05). Conclusion: These results indicate the relationship between demographic factors such as weight, age and gender, brain temperament, as well as some psychological factors such as sleep quality and anxiety with the severity of the COVID-19 disease.

The Effect of 12 Hz Extremely Low-frequency Electromagnetic Field on Visual Memory of Male Macaque Monkeys.

Introduction: Today, humans live in a world surrounded by electromagnetic fields. Numerous studies have been conducted to discover the biological, physiological, and behavioral effects of electromagnetic fields on humans and animals. Given the biological similarities between monkeys and humans, The present research aimed to examine Visual Memory (VM), hormonal, genomic, and anatomic changes, in the male rhesus macaques exposed to an Extremely Low-Frequency Magnetic Field (ELF-MF). Methods: Four male rhesus macaques (Macaca mulatta) were used. For the behavioral tests, the animals should be fasting for 17 hours. For the tests such as visual memory, the animal's cooperation was necessary. Using the radiation protocol, we exposed two monkeys to a 12-Hz electromagnetic field with a magnitude of 0.7 µT (electromagnetic radiation) four hours a day for a month. Before and after the exposure, a visual memory test was conducted using a coated device (visible reward) on a movable stand. Ten milliliters of blood was obtained from the femoral artery of each monkey, and half of it was used to examine cortisol serum levels using the MyBioSource kit (made in the USA). The other half of the blood was used to extract lymphocytes for assaying expressions of Glucocorticoid Receptor (GR) genes before and after radiation using the PCR method. Anatomic studies of the amygdala were carried out based on pre- and post-radiation Magnetic Resonance Imaging (MRI). Results: Research results indicated that visual memory in male primates increased significantly after exposure to the 12-Hz frequency. Hormonal analysis at the 12-Hz frequency showed a decrease in cortisol serum levels. However, visual memory and serum cortisol levels did not change considerably in male primates in the control group. There was no considerable amygdala volumetric difference after exposure to the 12-Hz frequency. The expression of the GR genes decreased in the 12-Hz group compared to the control group. Conclusion: In short, these results indicated that ELF might benefit memory enhancement because exposure to the 12-HZ ELF can enhance visual memory. This outcome may be due to a decrease in plasma cortisol and or expression of GR genes. Moreover, direct amygdala involvement in this regard cannot be recommended. Highlights: The effects of Extremely Low-Frequency Electromagnetic Fields (ELF-EMF) of 12 Hz on monkeys were studied.The results showed a reduction in the serum cortisol levels and the expression of GR genes.The amygdala anatomical area changes were not significant in the experimental group.In the experimental group, visual memory (delay of 30- and 60-s evaluation) improved after exposure to a frequency of 12 Hz. Plain Language Summary: Extremely low-frequency electromagnetic fields are among the most important factors affecting humans. This study aimed to determine the fields of 12-Hz frequency on the visual memory changes of male monkeys. The importance of research is due to the cognitive similarity of monkeys to humans. The findings of the research can be attributed to humans. Behavioral, hormonal, genetic, and anatomical studies indicated improvement in visual memory (test monkeys versus control monkeys). This study demonstrates the effect of the 12-Hz frequency on the monkey's visual memory. Researchers can study 12-Hz frequency in other cognitive indices.

Anxiogenic and anxiolytic effects of memantine injected into the ventral hippocampus in male stressed mice.

OBJECTIVES: The effects of intra-ventral hippocampal memantine administration in male NMRI stressed mice were studied. METHODS: Two stainless steel gauge 23 guide cannulas were placed in the middle part of the mice ventral hippocampus using stereotaxic coordination. Seven days later, the animals were undergone to the stress protocol as follows: They experience four consecutive electro-foot shock stress sessions lasting for 10 min. Five or 30 min before each stress session, the animals received intra-ventral hippocampal (0.1, 1 and, 5 µg/mouse) or intraperitoneal (1, 5, and 10 mg/kg) memantine respectively. Eight days after stress termination, the animals were tested either for the maintenance of either anxiety (elevated plus maze) or depression (forced swimming test). RESULTS: Animals show anxiety eight days after stress termination. Intra-ventral hippocampal infusion of memantine (5 µg/mouse) 5 min before stress inhibited the anxiety-like behaviors. However, other doses of the drug exacerbate the stress effect. The drug, when injected peripherally exacerbated the stress effect in all doses. The drug by itself had no effect. In addition, animals also show depression nine days after stress termination and memantine (0.1, 1, and 5 µg/mouse) reduced the stress effect. The drug (0.1 µg/mouse) by itself induced depression in the animals. However, the drug when injected peripherally reduced the stress effect in all doses. CONCLUSIONS: It could be concluded that NMDA glutamate receptors in the ventral hippocampus may play a pivotal role in the mediation of maintenance of anxiety and depression induced by stress in the mice.

Pre-Clinical Evaluation of the Nanoliposomal antiPCSK9 Vaccine in Healthy Non-Human Primates.

BACKGROUND: Our previous studies showed the safe preventive and therapeutic effects of immunization using the nanoliposomal antiPCSK9 vaccine called "Liposomal Immunogenic Fused PCSK9-Tetanus plus Alum adjuvant" (L-IFPTA), in mouse models of atherosclerosis. Here we aimed to ascertain the immunogenicity and safety of the L-IFPTA vaccine in a pre-clinical study in healthy non-human primates. METHODS: Five male rhesus macaque monkeys were subcutaneously immunized with the L-IFPTA vaccine, four times with bi-weekly intervals. To evaluate immunogenicity, the plasma antiPCSK9 antibody in immunized monkeys was detected and quantified using the ELISA method. The functionality of the induced antiPCSK9 antibodies was determined by the PCSK9/LDLR in vitro binding assay kit. The safety of the vaccine was tested using the evaluation of several major circulating indicators including plasma lipid alterations, inflammatory biomarkers and organ injury biomarkers. RESULTS: The resultant data indicated that the L-IFPTA vaccine significantly and highly induced the generation of functional and safe antiPCSK9 antibodies in immunized monkeys. Plasma levels of specific biomarkers indicating organ performance including creatinine, urea, uric acid, bilirubin, ALP, AS, ALT and TSH were not significantly altered. After immunization in healthy monkeys, non-prespecified endpoints (plasma levels of TC, LDL-C, VLDL-C and TG) were non-significantly reduced by 11.6 ± 36%; 16 ± 28%; 22 ± 53% and 24 ± 51%, respectively, while HDL-C was slightly increased by 2 ± 64%. There were also no significant changes in plasma levels of pro- and anti-inflammatory biomarkers. CONCLUSION: The L-IFPTA vaccine could efficiently stimulate the host humoral immune response to produce active antibodies that inhibit plasma PCSK9 while not provoking systemic inflammation and not adversely affecting organ performance.

The Effect of Brain Teaser Games on the Attention of Players Based on Hormonal and Brain Signals Changes.

INTRODUCTION: Computer games as an interactive media play a significant role in the cognitive and behavioral health of the players. Computer games have either positive or negative effects on cognitive indices among players. They also directly influence the lifestyle and quality of life of children, adolescents, and young adults. The present study aimed to evaluate the short-term effects of the brain teaser game on players. METHODS: Among 45 male volunteers, 40 subjects with an average age of 20 years were recruited and divided into two groups: the experimental group and the control group. All required tests were conducted before and after the intervention (playing the game) on the experimental group. Also, the same tests were performed on the control group, in which the participants were not allowed to play the game. All participants completed a questionnaire comprised demographic characteristics and specific information regarding the game (e.g., game style and hours spent on playing the game). The saliva samples were collected to measure levels of cortisol and α-amylase. The salivary α-amylase (sAA) and cortisol levels were analyzed using the relevant ELISA kits. The cognitive tests were performed using PASAT software before and after the game to assess the perceptual-cognitive abilities of the players. The brain waveforms were acquired by a 14-channel Emotiv brain signal recording device before and after the game. Data analysis was conducted in R and MATLAB software. RESULTS: PASAT test suggested that mental health and sustained attention were significantly improved after the intervention. In addition, the sAA and salivary cortisol levels were significantly higher before the intervention. The results of the brainwave analysis revealed that stress index and attention were significantly higher before the intervention. CONCLUSION: Findings of the present study suggest that brain teaser games positively influence the central nervous system and activate stress path, leading to changes in brain signals and subsequently improved cognitive elements, such as attention among players.

The effects of Valerian on sleep spindles in a model of neuropathic pain.

INTRODUCTION: Valeriana officinalis is known to be one of the most famous herbal supplements for the treatment of anxiety and insomnia. Despite its widespread use in most countries all around the world, there is little scientific information and research on how this medication affects sleep patterns, and there are almost no studies on its effects on the characteristics of sleep spindles. MATERIAL AND METHODS: The present study was conducted to investigate the effects of Valerian extract (VAL) on sleep spindles and induced anxiety in chronic neuropathic pain model in rats. 24 male rats were divided into three groups: neuropathic group (n=9) in which the rats underwent chronic constriction injury (CCI), sham group (n=7) in which the sciatic nerves of the animals were exposed without any constriction and also fed with the vehicle, and the third group was under CCI condition and treated with Valerian (n=8). All the rats underwent electrode implant surgery so that we could record electroencephalogram and electromyography waves. In all the three groups, EEG and EMG recordings were recorded three times (150min each time). The initial recording was just prior to the CCI surgery and the rest were 3 and 6 days following CCI surgery. Moreover, cold allodynia and elevated plus maze tests were performed 3 and 6 days following the CCI surgery. RESULTS: Valerian treatment could repair the allodynia induced by neuropathy. On the other hand, by Valerian treatment (400mg/kg) during neuropathy, the REM sleep, decreased and the non-REM sleep increased. Moreover, there was an increment in sleep spindle density and spindle frequency even in neuropathic condition. DISCUSSION: This herbal supplement improves the quality of sleep in neuropathy conditions.

The controlling role of nitric oxide within the shell of nucleus accumbens in the stress-induced metabolic disturbance.

CONTEXT AND OBJECTIVES: The involvement of the nitricergic system within the shell part of the nucleus accumbens (NAc) was evaluated in the metabolic disturbances due to stress. MATERIALS AND METHODS: Male Wistar rats were cannulated in the shell of the left NAc. They received either saline or different doses of L-arginine and/or L-NAME five minutes before each stress session, for four days. Plasma cortisol concentration, food and water intake, time elapsing for eating, animal weight changes and adrenal gland weight were recorded. RESULTS: The L-arginine 1 µg/rat decreased the level of cortisol, water and food intake and time of feeding and increased the adrenal weight. But L-NAME at 1 µg/rat had opposite effects on these factors. However, the drugs showed similar effects at 10 µg/rat. CONCLUSION: Injection of nitric oxide modifiers into the left side of NAc shell part may have an interactive role with sub-chronic stress in metabolic behaviour.

Changes in Cognitive Functions Following Violent and Football Video Games in Young Male Volunteers by Studying Brain Waves.

INTRODUCTION: This research investigated the effects of violent and football video games on cognitive functions, cortisol levels, and brain waves. METHODS: A total of 64 participants competed in a single-elimination tournament. Saliva samples of all players were obtained before and after the games for the assessment of cortisol levels. The cognitive performances of the players were also assessed by paced auditory serial addition test. Moreover, the electroencephalogram recording was conducted during the games. RESULTS: The results showed that salivary cortisol levels significantly decreased after playing both games. Also, playing the football game increased reaction time, whereas decreased sustained attention and mental fatigue. CONCLUSION: Conversely, following playing a violent game, the reaction time decreased, and sustained attention and mental fatigue increased. Furthermore, the results of the EEG recording revealed that playing a violent game engaged more brain regions than the football game. In conclusion, playing violent game more effectively improved cognitive performances in the players than the football game.

The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging".

PURPOSE: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by "inflamm-aging". It is highly likely that "inflamm-aging" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. RESULTS: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of "inflamm-aging", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection.

Stress-Induced Spatial Memory Deficit Reversed by Basolateral Amygdala NMDA Receptor Inhibition in Male Wistar Rats.

INTRODUCTION: The present study investigated the role of the Basolateral Amygdala (BLA) N-methyl-D-aspartate (NMDA) receptors in stress-induced spatial memory disturbance among the male Wistar rats. METHODS: The male Wistar rats (Average weight =200 g) were cannulated bilaterally in the BLA, and entered the study (n=6-8) after one week. They received seven electro-foot-shock stress sessions on seven consecutive days. Memantine (0.1, 1, and 5 µg/rat) or saline (0.5 µL/ rat) was injected into the BLA, five minutes before each stress session. The control groups received the same doses of memantine and no stress. After the end of the stress sessions, blood samples were taken from all animals to evaluate their plasma corticosterone. Also, the spatial learning and memory of the study animals were evaluated using the Barnes maze method. The animals experienced five consecutive days of training on the maze for spatial learning. On the sixth day, their spatial memory was evaluated on the maze. Time, distance, the number of errors, and the taking strategy for reaching the target hole were considered as the parameters for the spatial learning and memory evaluation. RESULTS: Stress increases the plasma corticosterone level, while memantine preadministration reduces the stress effects. Besides, stress increases the time and distance to the target hole and the number of errors. Stress changed the animals' strategy from serial to random type. However, the intra-BLA memantine reversed all the disturbances induced by the stress. CONCLUSION: This study indicated that the BLA glutamate NMDA receptors modulate the effect of stress on spatial learning and memory deficit.

SHELL Part of Nucleus Accumbens and Its Laterality Has Important Role in Response to Chronic Stress in Female Rats

Abstract The nucleus accumbens shell (NAcSh) plays a role in appetitive and negative motivation with sex differences in responses. NAcSh and its laterality in metabolic and hormonal responses to chronic stress in female rats is evaluated via transient inactivation of this nucleus during stress induction. Animals in the stress groups received consecutive stress for four days and transient inactivation of NAcSh was performed by administrating lidocaine (0.2%) unilaterally or bilaterally in the nucleus for five minutes before electric foot shock induction. After stress termination, food and water intake, latency to eat, plasma glucose, corticosterone, estradiol and progesterone were measured in all groups. Results showed that stress increased food intake and blood glucose level, but there were no change in the latency to eat and the amount of water intake. The right side, the left side, and both sides of NAcSh may be dominant in latency to eat, food intake, and both water intake and plasma glucose level, respectively. Although chronic stress included no changes for corticosterone and progesterone, it increased estradiol level in plasma. Also, bilateral and right sides of NAcSh may have modulatory effects on stress in corticosterone and progesterone, respectively, without affecting estradiol. It can be concluded that the NAc shell plays a pivotal role in metabolic and hormonal responses to chronic stress in a laterality manner in female rats.