The effect of olanzapine on spatial memory impairment, depressive-like behavior, pain perception, and BDNF and synaptophysin expression following childhood chronic unpredictable mild stress in adult male and female rats.

Chronic unpredictable mild stress (CUMS) method has been introduced as a rodent model of depression. On the other hand, olanzapine, as an antipsychotic, can induce antidepressant and antipsychotic effects. Also, olanzapine may improve cognitive functions. Both CUMS and olanzapine can also affect the expression level of brain-derived neurotrophic factor (BDNF) and synaptophysin, the molecular factors involved in synaptic function, and learning and memory. In this study, we investigated the effect of olanzapine on locomotor activity (using open field test), pain threshold (using hot plate), depressive-like behavior (using forced swim test), spatial learning and memory (using Morris water maze), and BDNF and synaptophysin hippocampal expression (using real-time PCR) in both male and female CUMS rats. CUMS was performed for three consecutive weeks. Olanzapine was also injected intraperitoneally at the dose of 5 mg/kg. Our data showed that olanzapine can reverse the effects of CUMS on behavioral functions and BDNF and synaptophysin expression levels in the hippocampus of both males and females. It was also shown that olanzapine effects on spatial memory, pain perception, and BDNF and synaptophysin level were stronger in females than males. In conclusion, we suggested that the therapeutic effects of olanzapine in CUMS rats may be closely related to the function of BDNF and synaptophysin. Also, the therapeutic effects of olanzapine may be stronger in females. Therefore, and for the first time, we showed that there may be a sex difference in the effects of olanzapine on behavioral and molecular changes following CUMS.

Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).

Interaction effect of crocin and citalopram on memory and locomotor activity in rats: an insight into BDNF and synaptophysin levels in the hippocampus.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive-compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin.

Sex-controlled differences in sertraline and citalopram efficacies in major depressive disorder: a randomized, double-blind trial.

To investigate the response to antidepressants while controlling for sex, which has been controversial, 92 outpatient males and females with major depressive disorder were assigned to sertraline (100 mg/day) or citalopram (40 mg/day) in two strata and were assessed using Hamilton depression rating scale (HDRS) scores and brain-derived neurotrophic factor (BDNF), interleukin (IL)-6 and cortisol serum levels in this 8-week, randomized, parallel-group, double-blind clinical trial. Data of 40 sertraline and 40 citalopram recipients with equal representation of males and females assigned to each medication were analyzed, while their baseline characteristics were not statistically different (P > 0.05). There were no significant differences between sertraline and citalopram recipients in outcome changes (P > 0.05), all of which indicated improvement, but a significant time-treatment-sex interaction effect in BDNF levels was observed (P = 0.035). Regarding this, subgroup analyses illustrated a significantly greater increase in male BDNF levels following sertraline treatment (P = 0.020) with a moderate to large effect size (Cohen's d = 0.76 and ). Significant associations were observed between percentage changes in IL-6 levels and BDNF levels in sertraline recipients (P = 0.033) and HDRS scores in citalopram recipients (P < 0.001). Sex was an effect modifier in BDNF alterations following sertraline and citalopram administration. Further large-scale, high-quality, long-term studies are recommended.

Crocin (bioactive compound of Crocus sativus L.) potently restores REM sleep deprivation-induced manic- and obsessive-compulsive-like behaviors in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors including hyperlocomotion. On the other hand, crocin (one of the main compounds of Crocus sativus L. or Saffron) may be beneficial in the improvement of mental and cognitive dysfunctions. Also, crocin can restore the deleterious effects of SD on mental and cognitive processes. In this study, we investigated the effect of REM SD on female rats' behaviors including depression- and anxiety-like behaviors, locomotion, pain perception, and obsessive-compulsive-like behavior, and also, the potential effect of crocin on REM SD effects. We used female rats because evidence on the role of REM SD in modulating psychological and behavioral functions of female (but not male) rats is limited. REM SD was induced for 14 days (6h/day), and crocin (25, 50, and 75 mg/kg) was injected intraperitoneally. Open field test, forced swim test, hot plate test, and marble burying test were used to assess rats' behaviors. The results showed REM SD-induced manic-like behavior (hyperlocomotion). Also, REM SD rats showed decreased anxiety- and depression-like behavior, pain subthreshold (the duration it takes for the rat to feel pain), and showed obsessive compulsive-like behavior. However, crocin at all doses partially or fully reversed REM SD-induced behavioral changes. In conclusion, our results suggested the possible comorbidity of OCD and REM SD-induced manic-like behavior in female rats or the potential role of REM SD in the etiology of OCD, although more studies are needed. In contrast, crocin can be a possible therapeutic choice for decreasing manic-like behaviors.

Chronic REM sleep deprivation leads to manic- and OCD-related behaviors, and decreases hippocampal BDNF expression in female rats.

BACKGROUND: Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats. METHODS: The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg. RESULTS: REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior. CONCLUSIONS: Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated.

Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder.

Psilocybe cubensis is a species of psilocybin mushroom (magic mushroom) of moderate potency whose principal active compounds are psilocybin and psilocin. Recent studies have shown the significant procognitive and mood-enhancer effects of Psilocybe cubensis. However, evidence is so limited, especially in preclinical studies. We aimed to investigate the effect of Psilocybe cubensis extract on posttraumatic stress disorder (PTSD)-like behavior, pain perception, locomotor activity, and anxiety in a rat model of PTSD. Male rats were exposed to three consecutive shocks (0.8 mA, 3 s interval) paired with three sounds broadcasted 3 s before delivering shocks (75 dB, 3 s). After 1, 3, or 21 days, freezing rate was measured in the fear-conditioning apparatus. Open filed test and hot plate were used to assess locomotor activity and anxiety, and pain subthreshold, respectively. Psilocybe cubensis was injected intraperitoneal at the dose of 25 mg/kg (single administration) before (pretrain) or after (posttrain) shocks, or before the test (pretest). Results showed psilocybin potently alleviated PTSD symptom is short- but not long-term after the induction of PTSD. Psilocybe cubensis decreased locomotor activity only in a short period after administration. Psilocybe cubensis also increased pain subthreshold and decreased anxiety. In conclusion, Psilocybe cubensis effects on PTSD-like behavior and locomotor activity seem to be remained in short-term, while Psilocybe cubensis effects on pain subthreshold and anxiety remained long-term. This is the first study evaluating the effect of Psilocybe cubensis on PTSD-like behavior in rats in three different time protocols (1, 3, and 21 days after fear conditioning). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sex difference affects fear extinction but not lithium efficacy in rats following fear-conditioning with respect to the hippocampal level of BDNF.

In rodents, exposure to electrical shock and creating a strong fear memory using fear-conditioning model can induce PTSD-like behavior. In this study, we induced a fear-conditioning model in rats and investigated freezing (PTSD-like) behavior, 21 days after three shocks exposure (0.6 mA, 3 s, 30 seconds interval) in both male and female rats. Lithium was injected intraperitoneally (100 mg/kg) in three protocols: (1) 1 h after fear-conditioning (2) 1 h, 24 h, and 48 h after fear-conditioning (3), 1 h, 24 h, 48 h, 72 h, and 96 h after fear-conditioning. Extinction training (20 sounds without shocks, 75 dB, 3 s, 30 seconds interval) was performed in three protocols: (1) 1 h after fear-conditioning (one session), (2) 1 h, 24 h, and 48 h after fear-conditioning (three sessions), (3), 1 h, 24 h, 48 h, 72 h, and 96 h after fear-conditioning (five sessions). Forced swim test (FST) and hot plate were used to assess behavior. Results showed that lithium in all protocols had no effect on freezing behavior, FST, and pain subthreshold in all rats. Extinction training decreased freezing behavior, with more efficacy in females. In males, only 5-session training was effective, while in females all protocols were effective. Extinction training also altered pain perception and the results of FST, depending on the sessions and was different in males and females. Brain-derived neurotrophic factor (BDNF) mRNA level was increased in females following 3 and 5 sessions, and in males following 5 sessions extinction training. In conclusion, we suggested that there is a sex difference for the effect of extinction training on freezing behavior and BDNF mRNA level in a rat model of fear-conditioning.

The effects of different acetylcholinesterase inhibitors on EEG patterns in patients with Alzheimer's disease: A systematic review.

OBJECTIVE: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. The early diagnosis of AD is an important factor for the control of AD progression. Electroencephalography (EEG) can be used for early diagnosis of AD. Acetylcholinesterase inhibitors (AChEIs) are also used for the amelioration of AD symptoms. In this systematic review, we reviewed the effect of different AChEIs including donepezil, rivastigmine, tacrine, physostigmine, and galantamine on EEG patterns in patients with AD. METHODS: PubMed electronic database was searched and 122 articles were found. After removal of unrelated articles, 24 articles were selected for the present study. RESULTS: AChEIs can decrease beta, theta, and delta frequency bands in patients with AD. However, conflicting results were found for alpha band. Some studies have shown increased alpha frequency, while others have shown decreased alpha frequency following treatment with AChEIs. The only difference was the type of drug. CONCLUSIONS: We found that studies reporting the decreased alpha frequency used donepezil and galantamine, while studies reporting the increased alpha frequency used rivastigmine and tacrine. It was suggested that future studies should focus on the effect of different AChEIs on EEG bands, especially alpha frequency in patients with AD, to compare their effects and find the reason for their different influence on EEG patterns. Also, differences between the effects of AChEIs on oligodendrocyte differentiation and myelination may be another important factor. This is the first article investigating the effect of different AChEIs on EEG patterns in patients with AD.

The effect of acute crocin on behavioral changes and BDNF expression level in socially isolated rats.

Social isolation is a reliable method used for the induction of depression and psychiatric disorders in rodents. It has been suggested that social isolation can lead to hyperlocomotion, as a schizophrenic-like symptom in rodents. On the other hand, crocin (the major constituent of Crocus sativus) induces a wide-range of neuroprotective and mood enhancer effects. In the present study, we aimed to investigate the effect of acute crocin on social isolation-induced behavioral changes and BDNF expression in the hippocampus. Novelty-suppressed feeding test, open field test, marble burying test, hot plate, forced swim test, and the shuttle box were used to assess anxiety-like behavior, locomotor activity, obsessive-compulsive-like (OCD-like) behavior, pain threshold, depressive-like behavior, and passive avoidance memory, respectively. Real-time PCR was used to assess BDNF hippocampal expression level. The results showed that social isolation decreased anxiety- and depressive-like behavior, pain threshold, and BDNF expression, and induced OCD-like behavior and hyperlocomotion. Crocin dose-dependently restored the effect of social isolation on pain threshold, locomotor activity, depressive-like behavior, OCD-like behavior, and BDNF expression. Passive avoidance memory performance was also unaffected. In conclusion, we showed a hyperlocomotion profile and OCD-like behaviors, and a robust decrease in pain threshold in socially isolated rats. It can be suggested that social isolation from adolescence induces a "hyperlocomotion state" that affects all the behavioral functions of rats. Also, the function of BDNF can be related to a hyperlocomotion state and OCD-like symptom. It seems that BDNF expression level can be related to the therapeutic effect of crocin.

Parkinson's Disease: A Narrative Review on Potential Molecular Mechanisms of Sleep Disturbances, REM Behavior Disorder, and Melatonin.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. There is a wide range of sleep disturbances in patients with PD, such as insomnia and rapid eye movement (REM) sleep behavior disorder (or REM behavior disorder (RBD)). RBD is a sleep disorder in which a patient acts out his/her dreams and includes abnormal behaviors during the REM phase of sleep. On the other hand, melatonin is the principal hormone that is secreted by the pineal gland and significantly modulates the circadian clock and mood state. Furthermore, melatonin has a wide range of regulatory effects and is a safe treatment for sleep disturbances such as RBD in PD. However, the molecular mechanisms of melatonin involved in the treatment or control of RBD are unknown. In this study, we reviewed the pathophysiology of PD and sleep disturbances, including RBD. We also discussed the potential molecular mechanisms of melatonin involved in its therapeutic effect. It was concluded that disruption of crucial neurotransmitter systems that mediate sleep, including norepinephrine, serotonin, dopamine, and GABA, and important neurotransmitter systems that mediate the REM phase, including acetylcholine, serotonin, and norepinephrine, are significantly involved in the induction of sleep disturbances, including RBD in PD. It was also concluded that accumulation of α-synuclein in sleep-related brain regions can disrupt sleep processes and the circadian rhythm. We suggested that new treatment strategies for sleep disturbances in PD may focus on the modulation of α-synuclein aggregation or expression.

Mood and behavior regulation: interaction of lithium and dopaminergic system.

Lithium is one of the most effect mood-stabilizing drugs prescribed especially for bipolar disorder. Lithium has wide range effects on different molecular factors and neural transmission including dopaminergic signaling. On the other hand, mesolimbic and mesocortical dopaminergic signaling is significantly involved in the pathophysiology of neuropsychiatric disorders. This review article aims to study lithium therapeutic mechanisms, dopaminergic signaling, and the interaction of lithium and dopamine. We concluded that acute and chronic lithium treatments often reduce dopamine synthesis and level in the brain. However, some studies have reported conflicting results following lithium treatment, especially chronic treatment. The dosage, duration, and type of lithium administration, and the brain region selected for measuring dopamine level were not significant differences in different chronic treatments used in previous studies. It was suggested that lithium has various mechanisms affecting dopaminergic signaling and mood, and that many molecular factors can be involved, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), ß-catenin, protein kinase B (Akt), and glycogen synthase kinase-3 beta (GSK-3ß). Thus, molecular effects of lithium can be the most important mechanisms of lithium that also alter neural transmissions including dopaminergic signaling in mesolimbic and mesocortical pathways.

The effect of crocin on cholestasis-induced spatial memory impairment with respect to the expression level of TFAM and PGC-1α and activity of catalase and superoxide dismutase in the hippocampus.

Large evidence has shown that cholestasis has a wide-range of deleterious effects on brain function, and also, on neurocognitive functions including learning and memory. On the other hand, crocin (derived from Crocus sativus) is a medicinal natural compound that induces neuroprotective and precognitive effects. In this study, we aimed to evaluate the effect of crocin on spatial learning and memory in cholestatic rats with respect to the level of mitochondrial transcriptional factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), catalase (CAT), and superoxide dismutase (SOD) in the hippocampus of male Wistar rats. Bile duct ligation (BDL) was used to induce cholestasis. Y-maze apparatus was used to assess spatial memory performance and real-time PCR was used to assess TFAM and PGC-1α gene expression. Also, crocin was injected intraperitoneal at the doses of 15, 20, and 30 mg/kg for thirty days. The results showed that BDL impaired spatial memory in rats. BDL also decreased SOD, TFAM, and PGC-1α level. In addition, crocin partially reversed the impairment effect of BDL on spatial memory. Crocin (30 mg/kg) also reversed the effect of BDL on SOD, TFAM, and PGC-1α. Of note, the effect of BDL on CAT activity was controversial. It seems that BDL can increase CAT activity. In addition, crocin (30 mg/kg) reversed the enhancement of CAT following BDL to its control level. In conclusion, crocin may induce a significant neuroprotective effect on cholestasis-induced memory impairment.

The Interaction Effect of Sleep Deprivation and Treadmill Exercise in Various Durations on Spatial Memory with Respect to the Oxidative Status of Rats.

Sleep deprivation (SD) has deleterious effects on cognitive functions including learning and memory. However, some studies have shown that SD can improve cognitive functions. Interestingly, treadmill exercise has both impairment and improvement effects on memory function. In this study, we aimed to investigate the effect of SD for 4 (short-term) and 24 (long-term) hours, and two protocols of treadmill exercise (mild short-term and moderate long-term) on spatial memory performance, and oxidative and antioxidant markers in the serum of rats. Morris Water Maze apparatus was used to assess spatial memory performance. Also, SD was done using gentle handling method. In addition, the serum level of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) was measured. The results showed that 24 h SD (but not 4 h) had negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Long-term moderate (but not short-term mild) treadmill exercise had also negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Interestingly, both protocols of treadmill exercise reversed spatial memory impairment and oxidative stress induced by 24 h SD. In conclusion, it seems that SD and treadmill exercise interact with each other, and moderate long-term exercise can reverse the negative effects of long-term SD on memory and oxidative status; although, it disrupted memory function and increased oxidative stress by itself.

Effect of RehaCom cognitive rehabilitation software on working memory and processing speed in chronic ischemic stroke patients.

Stroke survivors need assistance to overcome cognitive impairments. Working memory (WM) and processing speed (PS) as two critical cognitive functions are disrupted by stroke. The goal of this study was to investigate the effect of RehaCom rehabilitation software on WM and PS in participants with chronic ischemic stroke with hemiplegia (right/left side). Participants were selected among stroke patients who were referred to our special rehabilitation clinic. Fifty participants were assigned to control (n = 25) and experimental (n = 25) groups. The results of the experimental group were compared with the control group before and after the treatment with RehaCom (ten 45-min sessions across five weeks, two sessions per week). The results showed a significant improvement in WM and PS in the experimental group in comparison with the control group after a 5-week training with RehaCom. In conclusion, our findings indicate that treatment with RehaCom software improves WM and PS in chronic ischemic stroke participants with hemiplegia. The exact mechanism of RehaCom is largely unknown and further studies are needed, but its effects on the function of brain regions involved in modulating cognitive functions such as the prefrontal cortex, cingulate cortex, and parietal cortex may be mechanisms of interest.

Do Sleep Disturbances have a Dual Effect on Alzheimer's Disease?

Sleep disturbances and Alzheimer's disease have deleterious effects on various physiological and cognitive functions including synaptic plasticity, oxidative stress, neuroinflammation, and memory. In addition, clock genes expression is significantly altered following sleep disturbances, which may be involved in the pathogenesis of Alzheimer's disease. In this review article, we aimed to discuss the role of sleep disturbances and Alzheimer's disease in the regulation of synaptic plasticity, oxidative stress, neuroinflammation, and clock genes expression. Also, we aimed to find significant relationships between sleep disturbances and Alzheimer's disease in the modulation of these mechanisms. We referred to the controversial effects of sleep disturbances (particularly those related to the duration of sleep deprivation) on the modulation of synaptic function and neuroinflammation. We aimed to know that, do sleep disturbances have a dual effect on the progression of Alzheimer's disease? Although numerous studies have discussed the association between sleep disturbances and Alzheimer's disease, the new point of this study was to focus on the controversial effects of sleep disturbances on different biological functions, and to evaluate the potential dualistic role of sleep disturbances in the pathogenesis of Alzheimer's disease.

Intricate role of sleep deprivation in modulating depression: focusing on BDNF, VEGF, serotonin, cortisol, and TNF-α.

In this review article, we aimed to discuss intricate roles of SD in modulating depression in preclinical and clinical studies. Decades of research have shown the inconsistent effects of SD on depression, focusing on SD duration. However, inconsistent role of SD seems to be more complicated, and SD duration cannot be the only one factor. Regarding this issue, we chose some important factors involved in the effects of SD on cognitive functions and mood including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), serotonin, cortisol, and tumor necrosis factor-alpha (TNF-α). It was concluded that SD has a wide-range of inconsistent effects on BDNF, VEGF, serotonin, and cortisol levels. It was noted that BDNF diurnal rhythm is significantly involved in the modulatory role of SD in depression. Furthermore, the important role of VEGF in blood-brain barrier permeability which is involved in modulating depression was discussed. It was also noted that there is a negative correlation between cortisol and BDNF that modulates depression. Eventually, it was concluded that TNF-α regulates sleep/wake cycle and is involved in the vulnerability to cognitive and behavioral impairments following SD. TNF-α also increases the permeability of the blood-brain barrier which is accompanied by depressive behavior. In sum, it was suggested that future studies should focus on these mechanisms/factors to better investigate the reasons behind intricate roles of SD in modulating depression.

Evidence for Anti-inflammatory Effects of Adalimumab in Treatment of Patients With Major Depressive Disorder: A Pilot, Randomized, Controlled Trial.

BACKGROUND: Literature has suggested that major depressive disorder (MDD) is accompanied by higher concentrations of inflammatory biomarkers, which could sabotage response to conventional treatments. AIMS: This study aimed to evaluate the efficacy and safety of adalimumab adjunct to sertraline in adults with MDD and increased levels of systemic inflammation. METHODS: In a 6-week, randomized, double-blind, placebo-controlled trial, 36 patients with MDD and high-sensitivity C-reactive protein ≥3 mg/L were equally assigned to receive sertraline plus either adalimumab or placebo. Participants were assessed using the Hamilton Depression Rating Scale (HAM-D) at baseline, week 3, and week 6. Moreover, serum concentrations of inflammatory biomarkers were measured at baseline and trial end point. Finally, patients were assessed for any adverse event during the trial. RESULTS: Fifteen patients in each group completed the trial course. All baseline characteristics of participants were similar between the groups. Adalimumab adjunct to sertraline resulted in a greater improvement in HAM-D score compared with placebo over the trial period ( P < 0.001). Participants receiving adalimumab significantly experienced greater response to treatment (≥50% reduction in the HAM-D score) than those receiving placebo ( P = 0.042). Furthermore, after 6 weeks of adalimumab combination therapy with sertraline, inflammatory biomarkers significantly decreased ( P ≤ 0.001), whereas no significant alteration was found in the placebo group. No serious adverse event was documented in the treatment arms. CONCLUSIONS: Adalimumab adjunctive therapy remarkably improves depressive symptoms of patients with MDD. Further investigations with larger sample sizes and longer follow-up periods are required to confirm the findings.

Effect of multi-epitope derived from HIV-1 on REM sleep deprivation-induced spatial memory impairment with respect to the level of immune factors in mice.

Objectives: Sleep deprivation (SD) has a negative impact on cognitive functions including learning and memory. Many studies have shown that rapid-eye-movement (REM) SD also disrupts memory performance. In this study, we aimed to investigate the effect of multi-epitope Gag-Pol-Env-Tat derived from Human immunodeficiency virus 1 (HIV-1) on REM SD-induced spatial memory impairment with respect to the levels of interleukin-4 (IL-4), interleukin-17 (IL-17), interferon-gamma (IFN-γ), immunoglobulin G1 (IgG1), immunoglobulin G2a (IgG2a), and lymphocyte proliferation in NMRI mice. We used multi-epitope Gag-Pol-Env-Tat derived from HIV-1 because Gag-Pol-Env-Tat immunogen sequence is one of the most sensitive immunogen sequences of HIV-1 that can significantly augment cellular and humoral immune systems, leading to the improvement of cognitive functions. Materials and Methods: Morris water maze apparatus was used to assess spatial memory, and multi-platform apparatus was used to induce RSD for 24 hr. Multi-epitope derived from HIV-1 was subcutaneously injected at the dose of 20 µgr/ml, once and fourteen days before RSD. Results: RSD impaired spatial memory and injection of multi-epitope derived from HIV-1 reversed this effect. RSD decreased IL-4, IgG1, and IgG2a levels, while multi-epitope derived from HIV-1 reversed these effects. Multi-epitope derived from HIV-1 also increased lymphocyte proliferation and decreased IL-17 levels in both control and RSD mice. Conclusion: Multi-epitope derived from HIV-1 may improve memory performance via induction of anti-inflammatory immune response.

Night shift hormone: How does melatonin affect depression?

Melatonin is the main hormone secreted by the pineal gland that modulates the circadian rhythm and mood. Previous studies have shown the therapeutic effects of melatonin, or its important analogue, agomelatine, on depression. In this review study, we aimed to discuss the potential mechanisms of melatonin involved in the treatment of depression. It was noted that disrupted circadian rhythm can lead to depressive state, and melatonin via regulating circadian rhythm shows a therapeutic effect. It was also noted that melatonin induces antidepressant effects via promoting antioxidant system and neurogenesis, and suppressing oxidative stress, neuroinflammation, and apoptosis. The interaction effect between melatonin or agomelatine and serotonergic signaling has a significant effect on depression. It was noted that the psychotropic effects of agomelatine are induced by the synergistic interaction between melatonin and 5-HT2C receptors. Agomelatine also interacts with glutamatergic signaling in brain regions involved in regulating mood and circadian rhythm. Interestingly, it was concluded that melatonin exerts both pro- and anti-inflammatory effects, depending on the grade of inflammation. It was suggested that synergistic interaction between melatonin and 5-HT2C receptors may be able to induce therapeutic effects on other psychiatric disorders. Furthermore, dualistic role of melatonin in regulating inflammation is an important point that can be examined at different levels of inflammation in animal models of depression.