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Oxycodone is widely used for pain management and acts via binding to mu- and kappa opioid receptors. It was shown that extended oxycodone usage can result from the demyelination and degeneration of neurons through the stress response, which triggers apoptotic signaling pathways. The striatum and cerebellum are recognized as significant contributors to addiction; however, there is no report on the effect of oxycodone on the cerebellum and striatum and motor coordination. We treated rats daily with oxycodone at 15 mg/kg doses for thirty days. Motor performance and electromyography activity were then evaluated. Stereological methods were performed to assess the number of neurons in the cerebellum and striatum as well as immunohistochemistry for microgliosis and astrogliosis. Furthermore, the Sholl analysis method was utilized to evaluate the cellular structure of both microglia and astrocytes. Results of the rotarod test for motor coordination show no significant (P < 0.05) difference between the oxycodone subjects and those in the control group. In addition, open-field assessments indicated that the application of oxycodone did not alter the amount of distance covered (as an indicator of locomotion) or time spent in the central area (as an indicator of anxiety) (P < 0.001). The electromyography (EMG) test result showed that oxycodone caused a delay in the reaction of the muscular nerves (P < 0.001). Data and results from our experiment revealed that administering oxycodone did not affect astrogliosis and the number of neurons in the cerebellum and striatum (P < 0.05). In contrast, it altered neuromuscular function. In addition, oxycodone administration activated microglia in the cerebellum and striatum. In conclusion, we encourage more research on the adverse effects of oxycodone on the brain. [ABSTRACT FROM AUTHOR]

The serotonin-1A receptors (5-HT1A) in the two cerebral hemispheres are differentially involved in memory. The distribution of 5-HT1A receptors in the left and right amygdala is different. Furthermore, evidence shows that the 5-HT1A receptors in the left and right amygdala work differently in memory function. The basolateral amygdala (BLA) also regulates hippocampal long-term potentiation (LTP) during stress. However, which BLA structure in each hemisphere underlies such lateralized function is unclear. The present research investigated the possible involvement of 5-HT1A lateralization in the BLA on stress-induced memory impairment. 5-HT1A receptor antagonist (Way-100-635) was injected into the left, right, or bilateral BLA twenty minutes before chronic restraint stress (CRS) for 14 consecutive days. Results indicated that suppression of 5HT1A-receptors in the BLA plays an essential role in reducing the acquisition of passive avoidance in the shuttle box test and spatial memory in the Barnes maze test in the stress animals. This decrease was significant in the CRS animals with left and bilateral suppressed 5HT1A-receptors in the BLA. Field potential recording results showed that the left, right, and bilateral injection of Way-100-635 into the BLA significantly reduced the slope and amplitude of fEPSP in the CA1 area of the hippocampus in stressed rats. No significant difference was observed in neuronal arborization in the CA1 area of the hippocampus. In conclusion, the 5-HT1A receptor in the left and right sides of BLA nuclei play a different role in memory consolidation in the hippocampus under stress. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Behavioral and functional studies describe hemispheric asymmetry in anxiety and metabolic behaviors in responses to stress. However, no study has reported serotonergic receptor (the 5-HT1A receptor) lateralization in the basolateral amygdala (BLA) in vivo on anxiety and metabolic behaviors under stress. In the present study, the effect of unilateral and bilateral suppression of the 5-HT1A receptor in the BLA on anxiety, and metabolic responses to chronic restraint stress was assessed. Male Wistar rats 7 days after cannulation into the BLA received chronic restraint stress for 14 consecutive days. 20 minutes before induction of stress, WAY-100–635 (selective 5-HT1A antagonist) or sterile saline (vehicle) was administered either uni- or bi-laterally into the BLA. Behavioral (elevated plus maze; EPM, and open field test), and metabolic parameter studies were performed. Results showed that stress causes a significant increase in weight gain compared to control. In the non-stress condition, the left and bilaterally, and in the stress condition the right, left, and both sides, inhibition of 5-HT1A in the BLA reduced weight gain. In the restraint stress condition, only inhibition of the 5-HT1A receptor in the left BLA led to decreased food intake compared to the control group. In stress conditions, inhibition of the 5-HT1A receptor on the right, left, and bilateral BLA increased water intake compared to the stress group. Inhibition of the 5-HT1A receptor on the left side of the BLA by WAY-100–635 induced anxiety-like behaviors in stressed rats. Similarly, WAY-100–635 on the left BLA effectively caused anxiety-like behaviors in both EPM and open field tests in the control animals. In conclusion, it seems that 5-HT1A receptors in the left BLA are more responsible for anxiety-like behaviors and metabolic changes in responses to stress. [ABSTRACT FROM AUTHOR]

Using nutritional interventions to cure and manage psychiatric disorders is a promising tool. In this regard, accumulating documents support strong relationships between the diet and brain health throughout the lifespan. Evidence from animal and human studies demonstrated that β-alanine (Beta-alanine; BA), a natural amino acid, provides several benefits in fight against cognitive decline promoting mental health. This review summarizes and reports state-of-the-art evidence on how BA affects cognitive health and argues existence of potential unrevealed biochemical mechanisms and signaling cascades. There is a growing body of evidence showing that BA supplement has a significant role in mental health mediating increase of the cell carnosine and brain-derived neurotrophic factor (BDNF) content. BDNF is one of the most studied neurotrophins in the mammalian brain, which activates several downstream functional cascades via the tropomyosin-related kinase receptor type B (TrkB). Activation of TrkB induces diverse processes, such as programmed cell death and neuronal viability, dendritic branching growth, dendritic spine formation and stabilization, synaptic development, cognitive-related processes, and synaptic plasticity. Carnosine exerts its main effect via its antioxidant properties. This critical antioxidant also scavenges hypochlorous acid (HOCl), another toxic species produced in mammalian cells. Carnosine regulates transcription of hundreds of genes related to antioxidant mechanisms by increasing expression of the nuclear erythroid 2-related factor 2 (Nrf2) and translocating Nrf2 to the nucleus. Another major protective effect of carnosine on the central nervous system (CNS) is related to its anti-glycating, anti-aggregate activities, anti-inflammatory, metal ion chelator activity, and regulation of pro-inflammatory cytokine secretion. These effects could be associated with the carnosine ability to form complexes with metal ions, particularly with zinc (Zn2+). Thus, it seems that BA via BDNF and carnosine mechanisms may improve brain health and cognitive function over the entire human lifespan. [ABSTRACT FROM AUTHOR]

In traditional medicine, Tarooneh (a hardcover of the date palm; Phoenix dactylifera) has known as a sedative and relaxant medicine. In this study, we evaluated the protective effects of Tarooneh in the anxiety-like behavior, cognitive deficit, and neuronal damages in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and frontal cortex neurons employing a rat model of chronic restraint stress. The animal received Tarooneh extract for 14 consecutive days in water, and chronic restraint stress was performed daily during this period. The results of the Barnes maze test showed that treatment with Tarooneh significantly improves spatial memory parameters such as latency time to find the target hole, number of errors, and distance traveling compared to the stress group. The EPM results showed that Tarooneh significantly increased the time spent in open arms and the percentage of entries into open arms and significantly decreased the frequency of head dipping behavior compared to animals in the stress group. Golgi–Cox staining indicates that loss of neural spine density in DG, CA1, CA3, and frontal cortex due to chronic restraint stress, was prevented with daily administration of Tarooneh. The results of cresyl-violet staining indicate that Tarooneh significantly increased the number of CV-positive neurons in the frontal cortex and CA1 region of the hippocampus compared to the stress group. Our results suggest that Tarooneh potentially prevented and improved effects in anxiety-like behavior, memory impairment, and synaptic plasticity loss in frontal and hippocampal neurons induced by chronic restraint stress. In conclusion, our results suggest that Tarooneh prevented and improved anxiety-like behavior, cognitive deficit, and neuronal damages in the CA1, CA3, and DG regions of the hippocampus and frontal cortex neurons induced by chronic restraint stress. [ABSTRACT FROM AUTHOR]

Background: Due to the complications related to the use of the current pharmacological approach for the alleviation of neuropathic pain, searching for effective compound with fewer complications is a requirement of the present era. It is well known that the pathophysiological mechanism of neuropathic pain is related to excessive inflammation in the nervous system. Hence, the present study focuses on whether the potential analgesic effects of Terminalia chebula (TC) extract are mediated by the changes in the protein expression of nerve growth factor (NGF) and nuclear factor-kappa B (NF-κB) in the brain in a rat model of sciatic nerve chronic constriction injury (CCI). Method and Results: Neuropathic pain was induced by the left sciatic nerve CCI. Male Wistar rats were assigned to three groups: sham, CCI, and CCI + TC (40 mg/kg). Animals received either normal saline (1 mL) or the aqueous-alcoholic extract of TC (40 mg/kg) for 30 days via gavage needles once a day. Cold allodynia and anxiety-like behaviors were examined one day before CCI surgery (day − 1), as well as days 2, 7, 14, and 30 following CCI. We also assessed the effects of the TC extract oxidative stress markers on day 30 following CCI. Moreover, a western blot analysis was performed on day 30 following CCI to evaluate the effects of the TC extract on the protein expression of NGF and NF-κB in the brain. Oral gavage of the TC extract significantly decreased cold allodynia on days 2 and 14 following CCI. Additionally, the CCI model of chronic pain significantly increased the protein expression of NGF and NF-κB in the brain on day 30 following CCI. Furthermore, the TC extract significantly decreased the protein expression of NGF and NF-κB in the brain. The TC extract also significantly increased the brain glutathione (GSH) content and decreased the malondialdehyde (MDA) content. Conclusion: It is suggested that the analgesic effects of the TC extract are mediated by the suppression of brain NGF, NF-κB, and by its antioxidant activity in the brain following neuropathic pain in rats. [ABSTRACT FROM AUTHOR]

Background: Despite the high prevalence of communicational differences, anxiety, and sensory processing difficulties in children with autism spectrum disorder (ASD), little is known about the nature of their experiences. Thus, the present study aimed to explore the correlation between communication skills, sensory difficulties, and anxiety in children with ASD. Fifty-three children with ASD (Mage = 8.51, SD = 2.51; males = 42) were recruited. The Persian version of the Short Sensory Profile (SSP), the Children's Communication Checklist (CCC), and the Spence Children's Anxiety Scale (SCAS) was used to assess the variables. Results: The overall sensory score of children with ASD was significantly and positively correlated with most of the communication skills (P < 0.05). The overall sensory score of children with ASD was significantly and negatively correlated with all anxiety subsets of these children (P < 0.05). The social relationships score of children with ASD had a significant and negative correlation with all subsets of anxiety and a significant and positive correlation with all sensory subsets (P < 0.05). The total score of communication was significantly and negatively related to all subsets of anxiety except separation anxiety (P < 0.05). Conclusions: Sensory processing difficulties in ASD children appear to be significantly associated with communication skills and anxiety acts as a mediator between the two. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) as a psychiatric illness negatively affects the behavior and daily life of the patients.Therefore, the early MDD diagnosis can help to cure the patients more efficiently and prevent adverse effects, although its unclear manifestations make the early diagnosis challenging. Nowadays, many studies have proposed automatic early MDD diagnosis methods based on electroencephalogram (EEG) signals. This study also presents an automated EEG-based MDD diagnosis framework based on Dictionary learning (DL) approaches and functional connectivity features. Firstly, a feature space of MDD and healthy control (HC) participants were constructed via functional connectivity features.Next, DL-based classification approaches such as Label Consistent K-SVD (LC-KSVD) and Correlation-based Label Consistent K-SVD (CLC-KSVD) methods, were utilized to perform the classification task. A public dataset was used, consisting of EEG signals from 34 MDD patients and 30 HC subjects, to evaluate the proposed method. To validate the proposed method, 10-fold cross-validation technique with 100 iterations was employed, providing accuracy (AC), sensitivity (SE), specificity (SP), F1-score (F1), and false discovery rate (FDR) performance metrics. The results show that LC-KSVD2 and CLC-KSVD2 performed efficiently in classifying MDD and HC cases. The best classification performance was obtained by the LCKSVD2 method, with average AC of 99.0%, SE of 98.9%, SP of 99.2%, F1 of 99.0%, and FDR of 0.8%. According to the results, the proposed method provides an accurate performance and, therefore, it can be developed into a computer-aided diagnosis (CAD) tool for automatic MDD diagnosis. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on irisin and expression of myogenic markers (paired box 7 (Pax7), myogenic differentiation 1 (MyoD), myogenin) in skeletal muscle of diabetic rats. Eighty-four male Wistar rats (6 weeks of age) were randomly divided into seven groups (n = 12): basic control (Co Basic), 8 weeks control (Co 8w), diabetes mellitus (DM), HIIT, DM + HIIT, MICT, and DM + MICT groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). The V ˙ o 2 max protocol was characterized by running on a rodent treadmill with moderate intensity (60–70% V ˙ o 2 max ), 60 min per session, 5 days/week, for 6 weeks. HIIT consisted of six 3-min runs at a high intensity (80–90% V ˙ o 2 max ) alternated with 2-min running at low intensity (50% V ˙ o 2 max ), 30 min per session, 5 days/week, for 6 weeks. Results showed that DM decreased myoblast markers compared to Co Basic and Co 8w groups. Fibronectin type III domain-containing protein 5 (FNDC5) mRNA decrease was correlated with myoblast markers (Pax7 r = 0.632, p = 0.027; MyoD r = 0.999, p = 0.001; myogenin r = 1.000, p = 0.001) in DM group. DM + MICT significantly increased gene expression of MyoD, myogenin, and FNDC5 compared to DM and DM + HIIT. The results also showed that the intensity and duration of exercise on the treadmill were effective in stimulating irisin and myogenic markers after DM. [ABSTRACT FROM AUTHOR]

Low-level laser therapy (LLLT) and methylene blue (MB) were proved to have neuroprotective effects. In this study, we evaluated the preventive effects of LLLT and MB alone and in combination to examine their efficacy against sleep deprivation (SD)–induced cognitive impairment. Sixty Balb/c male mice were randomly divided into five groups as follows: wide platform (WP), SD, LLLT, MB, LMB (treatment with both LLLT and MB). Daily MB (0.5 mg/kg) was injected for ten consecutive days. An 810-nm, 10-Hz pulsed laser was used in LLLT every other day. We used the T-maze test, social interaction test (SIT), and shuttle box to assess learning and memory and PSD-95, GAP-43, and synaptophysin (SYN) markers to examine synaptic proteins levels in the hippocampus. Our results showed that SD decreased alternation rate in the T-maze test, sociability and social novelty in SIT, and memory index in the shuttle box. Single treatments were not able to reverse these in most of the behavioral parameters. However, behavioral tests showed a significant difference between combined therapy and the SD group. The levels of synaptic plasticity markers were also significantly reduced after SD. There was a significant difference between the MB group and SD animals in GAP-43 and SYN biomarkers. Combination treatment with LLLT and MB also increased GAP-43, PSD-95, and SYN compared to the SD group. We found that the combined use of LLLT and MB pretreatment is more effective in protecting SD-induced cognitive impairment, which may be imparted via modulation of synaptic proteins. [ABSTRACT FROM AUTHOR]

Learned helplessness (LH) induces cognitive and emotional abnormalities via alteration of synaptic and apoptotic markers in the hippocampus. Given the sericin's neuroprotective effects on different experimental models, this study aimed to address whether sericin is able to reduce LH-induced behavioral and molecular changes in the mouse model. Sixty male mice (3 months old) were randomly divided into control, normal saline (NS), and/or different doses of sericin (Ser [100, 200, and 300 mg/kg]) for 21 days. Accordingly, the animals in NS and sericin-treated groups were subjected to 1 day learned helplessness protocol. Behavioral deficits were evaluated and alterations in both synaptic and apoptotic factors were evaluated in the hippocampus. Induction of LH was associated with behavioral changes (depression and cognitive impairment). On the other hand, the administration of sericin effectively normalized these deficits. At molecular levels, sericin increased the levels of synaptophysin, synapsin-1, and PSD-95, and decreased apoptosis in the hippocampus. Although the exact mechanisms underlying the neuroprotective effects of sericin are not fully understood, our results showed that this effect mediated via modulation of the synaptic and apoptotic proteins in the hippocampus of LH-subjected mice. [ABSTRACT FROM AUTHOR]

Background: The increase in fibronectin type-III domain-containing protein 5 (FNDC5), myonectin, and glucose transporter 4 (GLUT4) leads to a decrease in diabetes; meanwhile, exercise training can affect these factors. The result regarding the comparison between the effect of high-intensity interval training (HIIT) and that of moderate-intensity continuous training (MICT) is confusing. Thus, the present study investigated the comparative effects of HIIT and MICT on soleus muscle FNDC5, myonectin, and GLUT4 gene expressions in the diabetic rat model. Methods and results: Seventy-two male Wistar rats (weight 200 g ± 20) were randomly and equally assigned to six groups: control-healthy, MICT-healthy, HIIT-healthy, control-diabetes, MICT-diabetes, and HIIT-diabetes. At the first level, Streptozotocin (STZ) was utilized to induce diabetes in rats (at a dose of 55 mg/kg). After that, the training groups performed HIIT and MICT programs on the rodent treadmill for 6 weeks (five-session/week). Twenty-four hours after the last intervention, soleus muscle was removed, and sent to a research facility for future examinations. HIIT and MICT increased the muscle FNDC5, myonectin, and GLUT4 gene expression compared to the control group (P < 0.05). The type of training had no significant effect on the FNDC5 (P > 0.05), while the MICT program induced a greater increase in the myonec ztin and GLUT4 compared to the HIIT program (P < 0.05). Meanwhile, a positive relationship between all variables was observed. Conclusions: Exercise training has a beneficial effect on diabetes conditions via the effect of FNDC5, myonectin, and GLUT4. Due to the correlation between myonectin and GLUT4 shown in the present study, physical activity may alter myonectin through its effect on GLUT requiring further investigation by subsequent studies. [ABSTRACT FROM AUTHOR]

Objective: Coronavirus disease 2019 (COVID-19) is a world-wide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, treatment of severe COVID-19 is far from clear. Therefore, it is urgent to develop an effective option for the treatment of patients with COVID-19. Most patients with severe COVID-19 exhibit markedly increased serum levels of pro-inflammatory cytokines, including interferon (IFN)-α, IFN-γ, and interleukin (IL)-1β. Immunotherapeutic strategies have an important role in the suppression of cytokine storm and respiratory failure in patients with COVID-19. Methods: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar preprint database using all available MeSH terms for Coronavirus, SARS-CoV-2, anti-rheumatoid agents, COVID-19, cytokine storm, immunotherapeutic drugs, IFN, interleukin, JAK/STAT inhibitors, MCP, MIP, TNF. Results: Here, we first review common complications of COVID-19 patients, particularly neurological symptoms. We next explain host immune responses against COVID-19 particles. Finally, we summarize the existing experimental and clinical immunotherapeutic strategies, particularly anti-rheumatoid agents and also plasma (with a high level of gamma globulin) therapy for severe COVID-19 patients. We discuss both their therapeutic effects and side effects that should be taken into consideration for their clinical application. Conclusion: It is suggested that immunosuppressants, such as anti-rheumatoid drugs, could be considered as a potential approach for the treatment of cytokine storm in severe cases of COVID-19. One possible limitation of immunosuppressant therapy is their inhibitory effects on host anti-viral immune response. So, the appropriate timing of administration should be carefully considered. [ABSTRACT FROM AUTHOR]

Background: Organophosphorus agents are potent neurotoxins that widely used as insecticides and also as poison in warfare. In the current study, we examined the neuroprotective role of NMDA receptors in Paraoxon (POX)-induced neurotoxicity of hippocampal cultured neurons. Objective: Hippocampal neurons were isolated from the brains of neonatal rats. The cells treated with POX (100 µM) for 48 h or NMDA (NMDA receptor agonist, 100 µM) for 1 h or MK801 (NMDA receptor antagonist, 1 µM) for 15 min before the NMDA and POX treatment. The colorimetric MTS method was used for cell survival assay. The immunocytochemistry and scanning electron microscopy were done for the morphometric study and total neurotic length calculations. Additionally, the activity of the caspase-3 enzyme was determined. Result: The present results demonstrated that POX significantly reduces the viability of cells, cell number, length of neurites, and also the surface area of neurons. We also show that POX increased the activity of the Caspase3 enzyme. Additionally, the application of NMDA significantly increased the viability of cells, cell number, and the surface area of neurons as compared with the POX group. Furthermore, pretreatment of cells with NMDA significantly decreased the activity of the Caspase3 enzyme as compared with the POX group. Application of MK801 significantly decreased cell viability, cell number, TNL, and activity of Caspase3 enzyme as compared with the control group. Conclusion: The present study indicated that NMDA treatment has neuroprotective effects on hippocampal neurons following exposure to POX. It seems that these protective effects mediated by decrease the activity of caspase3. Additionally, pretreatment of cells with MK801 has toxicity effects on hippocampal neurons. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The basolateral amygdala (BLA) and hippocampus are part of the limbic fear–anxiety circuit and have also been implicated in the stress response. The BLA is rich in the expression of α1-adrenoceptors. We hypothesized that α1-adrenoceptors in BLA, may modulate stress-induced anxiety-like behavioral responses and hippocampal CA1 pyramidal neuron spine density. α1-Adrenoceptors agonist, phenylephrine, or antagonist, prazosin, were microinjected bilaterally into BLA of male Wistar rats 5 minutes before foot-shock stress. Then, anxiety-like behavioral responses to stress were measured on the Open Field Test (OFT) and on the Elevated Plus-maze (EPM). Also, Golgi-Cox staining was used to investigate the hippocampal CA1 pyramidal neuron spine density. The results showed that four consecutive day stress reduced the open arm time, and open arm entry in the EPM. Intra-BLA injection of prazosin reversed stress-induced anxiogenic-like behaviors. In the OFT stress decreased the center area entries and time, while intra-BLA injection of phenylephrine or prazosin did not alter these parameters. Stress also reduced the dendritic and axonal arborization in hippocampal CA1 pyramidal neurons. Interestingly, intra-BLA infusion of prazosin blocked the reduction in dendritic and axonal arborization induced by foot-shock stress. Taken together, stress produces anxiogenic-like behaviors and hippocampal CA1 pyramidal neurons morphology changes, which may be mediated through the BLA α1-adrenoceptors mechanism. [ABSTRACT FROM AUTHOR]

The prenatal stress during pregnancy has a wide variety of negative effects on the offspring behaviors. As such, in the present study the effect of prenatal immobilization stress was investigated on the brain BDNF level, spatial memory, anxiety and depression-like behavior in the F1 generation female NMRI mice. Twenty female pregnant mice were randomly allocated to stress and control groups (n = 10/group). The stress group was placed in PVC cylinders (2.5 cm in diameter and 20 cm in length) for one hour/day until the 15th day of pregnancy. The female F1 offspring was nursed by their mothers until reaching 25–30 g (9–10 weeks) which was tested for spatial memory, anxiety and depressive-like behavior using Barnes Maze, elevated plus-maze and forced swimming test, respectively. Also, the brain BDNF level was assessed by the ELISA method. Mice that underwent prenatal restraint stress exhibited impaired spatial memory in the Barnes Maze, which the time and distance to achieve the target hole and the number of errors in the female adult offspring increased than the control group. In the elevated plus-maze, the animals that underwent prenatal restraint stress spent less time in the open arms of the maze and reduced entering the open arms, compared to the control group. In addition, stress caused a significant decrease in swim time and a significant increase in float time for the female adult offspring compared to the control group. The brain BDNF concentration also decreased significantly in the stress group compared to the control group. This data suggests that prenatal stress may impair spatial memory and induce anxiety and depressive-like behavior in the adult offspring female mice via reducing brain BDNF. [ABSTRACT FROM AUTHOR]

Inhibitory GABAergic and excitatory glutamatergic neurons from multiple brain areas, send fibers to the hippocampal CA1 region. NMDA receptors have been identified as important compoents of the brain system underlying memory formation, which that through an increase in glutamate-mediated neurotransmission. Ketamine and other NMDA receptor antagonists produce deficits in cognitive tasks, including both spatial and non-spatial memory. In the current study, we tested whether the activation or inhibition of GABAA receptors in CA1 hippocampal of mice has an impact on ketamine (NMDA antagonist) induced spatial and non-spatial novelty detection deficits. Adult male mice weighing between 25–30 g were used. The open-field method was used to evaluate spatial and non-spatial memory information. Data obtained from the present study revealed that an intra-CA1 injection with a sub-threshold dose the GABAA receptor antagonist bicuculline (0.0625 µg mouse) disrupted spatial memory but restored non-spatial memory induced by lower and higher doses of ketamine (0.05 and 0.01 mg/kg) respectively. Meanwhile, the co-administration of the intra-CA1 injection with a sub-threshold dose of muscimol (GABAA receptor agonist at 0.25 µg/mouse) and a lower dose of ketamine could only impair the ability of non-spatial change detection but could not alter spatial novelty. In conclusion, ketamine (which contributes to the impairment of memory trace stored in the hippocampus) may be generated from GABAA receptors of CA1 neurons and their blockade could prevent these effects. [ABSTRACT FROM AUTHOR]

Background: The role of the amygdala in controlling emotional pain has been emphasized in several studies. In this study, the role of the NMDA glutamate receptors in the basolateral nucleus of the amygdala (BLA) in regulating inflammation and emotional pain, induced by formalin, was studied in male rats.Methods: Male Wistar rats, weighing 250±20 g, were injected with 20 μL of 2% formalin into the paw of the right hind limb. Memantine, at doses of 1 and 5 mg/rat, was injected bilaterally into the BLA five minutes prior to injecting formalin. Following the injection, the pain and inflammation of the paws were measured using Dubbison-Dennis and mercury immersion methods, respectively. The behavior of the animals, including licking time and foot volume, was assessed.Results: The results showed that the inactivation of the NMDA receptors in the BLA in the acute phase of pain reduced the licking time (the emotional aspect of pain). However, at a high dose (5 μg/rat), memantine exacerbates the pain induced by formalin in the chronic phase. Additionally, the inhibition of the NMDA receptors in the BLA by memantine enhanced the formalin-induced increase in foot volume (inflammation) in a dose-dependent manner.Conclusion: The study showed that the NMDA glutamate receptors in the BLA are crucial for the emotional pain and inflammation in both chronic and acute phases of formalin-induced pain. However, their roles are more pronounced in the chronic phase than in the acute phase of pain. [ABSTRACT FROM AUTHOR]

Due to an unfortunate oversight, one of the author names has been given erroneously. [ABSTRACT FROM AUTHOR]