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 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.

Crocin improved amyloid beta induced long-term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats.

Extracellular beta-amyloid (Aß) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long-term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP, and neuronal apoptosis using in vivo Aß models of the AD. The Aß peptide (1-42) was bilaterally administered into the frontal-cortex using stereotaxic apparatus. Five hours after surgery, rats were given intraperitoneal crocin (30 mg/kg) daily, which repeated for 12 days. Barnes maze results showed that administration of crocin significantly improves spatial memory indicators such as latency time to achieving the target hole and the number of errors when compared to Aß-group. Passive avoidance test revealed that crocin significantly increased the step-through-latency compared to Aß-treated alone. These learning deficits in Aß-treated animals correlated with a reduction of LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved population spike amplitude and mean field excitatory postsynaptic potentials (fEPSP) slope reduction induced by Aß. Neuronal apoptosis was detected by TUNEL assay and the expression levels of c-Fos proteins were examined by Western blotting. Crocin significantly reduced the number of TUNEL-positive cells in the CA1 region and decreased c-Fos in the hippocampus compared to Aß-group. In vivo Aß treatment altered significantly the electrophysiological properties of CA1 neurons and crocin further confirmed a neuroprotective action against Aß toxicity.

Psychotherapy for Medically Unexplained Pain: A Randomized Clinical Trial Comparing Intensive Short-Term Dynamic Psychotherapy and Cognitive-Behavior Therapy.

BACKGROUND: The efficacy of intensive short-term dynamic psychotherapy (ISTDP) for medically unexplained pain remains open to debate because of a paucity of high-quality studies. OBJECTIVES: This study sought to evaluate ISTDP as a treatment for medically unexplained pain in outpatients by comparing it with the established evidence-based cognitive-behavioral therapy (CBT) in a randomized clinical trial. METHODS: A total of 341 adults with medically unexplained pain were randomly assigned to 16 sessions of individual manualized CBT (N = 164) or ISTDP (N = 177). The groups were assessed at baseline, after 16 weeks of treatment, and at the 3-month follow-up. The primary outcome was perceived pain assessed using the numerical pain rating scale. The secondary outcomes were psychologic distress, depression, and cognitive variables. The cognitive variables included self-efficacy, catastrophizing, and coping strategies. RESULTS: In the intention-to-treat analysis, the ISTDP and CBT groups both showed improvement in the primary outcome after treatment. Pain symptoms in both conditions were significantly reduced. Both ISTDP and CBT groups demonstrated reductions in psychologic distress, depression and catastrophic thinking, and also increases in the use of relaxation as a coping strategy. The CBT group showed an improvement in self-efficacy that was not obtained in the ISTDP group. However, significant differences were not observed in the primary and secondary outcomes at the 3-month follow-up compared with posttreatment. Overall, both treatments were equally effective at the 3-month follow-up. CONCLUSION: Our results suggest that ISTDP may provide an effective alternative therapy for medically unexplained somatic symptoms of pain.

Effects of unilatral- and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine-induced place conditioning in male Wistar rat.

The rostral ventral tegmental area (VTAR) and central nucleus of amygdala (CeA) are considered the main regions for induction of psychological dependence on abused drugs, such as morphine. The main aim of this study was to investigate the transient inhibition of each right and left side as well as both sides of the VTAR and the CeA by lidocaine (2%) on morphine reward properties using the conditioned place preference (CPP) method. Male Wistar rats (250±20 g) 7 days after recovery from surgery and cannulation were conditioned to morphine (7.5 mg/kg) in CPP apparatus. Five minutes before morphine injection in conditioning phase, lidocaine was administered either uni- or bilaterally into the VTAR (0.25 µL/site) or CeA (0.5 µL/site). The results revealed that lidocaine administration into the left side, but not the right side of the VTAR and the CeA reduced morphine CPP significantly. The reduction was potentiated when lidocaine was injected into both sides of the VTAR and the CeA. The number of compartment crossings was reduced when lidocaine was injected into both sides of the VTAR and the CeA as well as the left side. Rearing was reduced when lidocaine was injected into the right, but not the left side of the VTAR. Sniffing and rearing increased when animals received lidocaine in the right side and reduced in the group that received lidocaine in the left side of the CeA. It was concluded that the right and the left side of VTAR and the CeA play different roles in morphine-induced activity and reward.

Common behaviors alterations after extremely low-frequency electromagnetic field exposure in rat animal model.

Naturally, the presence of electromagnetic waves in our living environment affects all components of organisms, particularly humans and animals, as the large part of their body consists of water. In the present study, we tried to investigate the relation between exposure to the extremely low-frequency electromagnetic field (ELF-EMF) and common behaviors such as body weight, food and water intake, anorexia (poor appetite), plasma glucose concentration, movement, rearing and sniffing in rats. For this purpose, rats were exposed to 40 Hz ELF-EMF once a day for 21 days, then at days 1, 3, 7, 14 and 21 after exposure, any changes in the above-mentioned items were assessed in the exposed rats and compared to the non-exposed group as control. Body weight of irradiated rats significantly increased only a week after exposure and decreased after that. No significant change was observed in food and water intake of irradiated rats compared to the control, and the anorexia parameter in the group exposed to ELF-EMF was significantly decreased at one and two weeks after irradiation. A week after exposure, the level of glucose was significantly increased but at other days these changes were not significant. Movements, rearing and sniffing of rats at day 1 after exposure were significantly decreased and other days these changes did not follow any particular pattern. However, the result of this study demonstrated that exposure to ELF-EMF can alter the normal condition of animals and may represent a harmful impact on behavior.

Terminalia chebula attenuates restraint stress-induced memory impairment and synaptic loss in the dentate gyrus of the hippocampus and the basolateral and central nuclei of the amygdala by inhibiting oxidative damage.

Chronic restraint stress induces cognitive abnormalities through changes in synapses and oxidant levels in the amygdala and hippocampus. Given the neuroprotective effects of fruit of Terminalia chebula (Halileh) in different experimental models, the present investigation aimed to address whether Terminalia chebula is able to reduce chronic restraint stress-induced behavioral, synaptic and oxidant markers in the rat model. Thirty-two male Wistar rats were randomly divided into four groups as follows: control (did not receive any treatment and were not exposed to stress), stress (restraint stress for 2 h a day for 14 consecutive days), Terminalia chebula (received 200 mg/kg hydroalcoholic extract of Terminalia chebula), and stress + Terminalia chebula groups (received 200 mg/kg extract of Terminalia chebula twenty minutes before stress) (n = 8 in each group). We used the shuttle box test to assess learning and memory, Golgi-Cox staining to examine dendritic spine density in the dentate gyrus region of the hippocampus and the basolateral and central nuclei of the amygdala, and total antioxidant capacity (TAC) and total oxidant status (TOS) in the brain. The shuttle box test results demonstrated that Terminalia chebula treatment had a profound positive effect on memory parameters, including step-through latency (STL) and time spent in the dark room, when compared to the stress group. Daily oral treatment with Terminalia chebula effectively suppressed the loss of neural spine density in the dentate gyrus region of the hippocampus and the basolateral and central nuclei of the amygdala caused by chronic restraint stress, as demonstrated by Golgi-Cox staining. Additionally, the results indicate that Terminalia chebula significantly reduced the TOS and increased TAC in the brain compared to the stress group. In conclusion, our results suggest that Terminalia chebula improved memory impairment and synaptic loss in the dentate gyrus of the hippocampus and the basolateral and central nuclei of the amygdala induced by restraint stress via inhibiting oxidative damage.

Time-dependent effect of oral morphine consumption on the development of cytotrophoblast and syncytiotrophoblast cells of the placental layers during the three different periods of pregnancy in Wistar rats.

UNLABELLED: Previous studies have shown that morphine abuse during pregnancy cancause a delay in the development of the placenta and embryo and also bring about birth defects. The present study investigates the effect of the duration of maternal morphine consumption during pregnancy, as well as the impacts of morphine abuse on the development of placental layers during the three different periods of pregnancy in Wistar rats. MATERIALS AND METHODOLOGY: Female Wistar rats have been used in the present study. Experimental groups received morphine (0.05 mg/mL of drinking water) after one night of coupling with male rats for mating. On 9th, 10th, and 14th days of pregnancy, pregnant animals were killed, and placentas were removed and fixed. The cells of the placentas layers were calculated by light microscope and MOTIC and SPSS software. RESULTS: The maternal surface thickness of the placenta was significantly increased, whereasthe fetal surface thickness of placenta was significantly decreased with morphine consumption with a time-dependent manner in experimental groups, compared to control groups. Moreover, the number of trophoblast cells increased in both maternal and fetal surfaces of placenta with respect to the duration of morphine consumption which was overt in the experimental groups compared to the control groups. CONCLUSION: In general, the time-dependent effects of oral morphine consumption can inhibit the development and natural functioning of cytotrophoblast and syncytiotrophoblast cells of the placental layers.

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.

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.

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.

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.

Oleuropein, chief constituent of olive leaf extract, prevents the development of morphine antinociceptive tolerance through inhibition of morphine-induced L-type calcium channel overexpression.

It has been shown that blockade of L-type calcium channels could abolish the development of opioid-induced antinociceptive tolerance. Here, the antitolerant effects of olive leaf extract (OLE) and its main component, oleuropein, which have a calcium channel blocker property were determined. Adult male Wistar rats were injected with morphine (20 mg/kg, i.p.) for 8 days to induce antinociceptive tolerance. Then OLE (50-200 mg/kg i.g.) and oleuropein (1-10 mg/kg i.p.) were injected concomitantly with morphine. The tail-flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of L-type calcium channel using semiquantitative RT-PCR. The results showed that OLE (200 mg/kg) completely prevented morphine tolerance development. In addition, oleuropein in dose of 10 mg/kg, but not in 5 mg/kg, prevented the development of morphine antinociceptive tolerance. In addition, a significant increase in the mRNA levels of calcium channel (43.9%) was observed in the lumbar spinal cord of tolerant animals, which was reversed by effective of dose OLE. In conclusion, the results indicate that olive leaf extract has a potential antitolerant property against the chronic usage of morphine and that its main component, oleuropein, is responsible for such effect.

The effects of low-level laser irradiation on differentiation and proliferation of human bone marrow mesenchymal stem cells into neurons and osteoblasts--an in vitro study.

Bone marrow-derived mesenchymal stem cells (BMSCs) are promising for use in regenerative medicine. Several studies have shown that low-level laser irradiation (LLLI) could affect the differentiation and proliferation of MSCs. The aim of this study was to examine the influence of LLLI at different energy densities on BMSCs differentiation into neuron and osteoblast. Human BMSCs were cultured and induced to differentiate to either neuron or osteoblast in the absence or presence of LLLI. Gallium aluminum arsenide (GaAlAs) laser irradiation (810 nm) was applied at days 1, 3, and 5 of differentiation process at energy densities of 3 or 6 J/cm(2) for BMSCs being induced to neurons, and 2 or 4 J/cm(2) for BMSCs being induced to osteoblasts. BMSCs proliferation was evaluated by MTT assay on the seventh day of differentiation. BMSCs differentiation to neurons was assessed by immunocytochemical analysis of neuron-specific enolase on the seventh day of differentiation. BMSCs differentiation to osteoblast was tested on the second, fifth, seventh, and tenth day of differentiation via analysis of alkaline phosphatase (ALP) activity. LLLI promoted BMSCs proliferation significantly at all energy densities except for 6 J/cm(2) in comparison to control groups on the seventh day of differentiation. LLLI at energy densities of 3 and 6 J/cm(2) dramatically facilitated the differentiation of BMSCs into neurons (p < 0.001). Also, ALP activity was significantly enhanced in irradiated BMSCs differentiated to osteoblast on the second, fifth, seventh, and tenth day of differentiation (p < 0.001 except for the second day). Using LLLI at 810 nm wavelength enhances BMSCs differentiation into neuron and osteoblast in the range of 2-6 J/cm(2), and at the same time increases BMSCs proliferation (except for 6 J/cm(2)). The effect of LLLI on differentiation and proliferation of BMSCs is dose-dependent. Considering these findings, LLLI could improve current in vitro methods of differentiating BMSCs prior to transplantation.

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.

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.

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.

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.

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.