Memory loss induced by lisdexamfetamine in the rat: A behavioral, electrophysiological, and histopathological Study.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.

Lateralization of the 5-HT1A receptors in the basolateral amygdala in metabolic and anxiety responses to chronic restraint stress.

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.

3-acetylpyridine induced behavioral dysfunction and neuronal loss in the striatum and hippocampus of adult male rats.

3-acetylpyridine (3-AP) is a neurotoxin that is known to mainly affect the inferior olivary nucleus (ION) in the brain stem. Although several studies have explored the effect of this neurotoxin, still further investigation is required to understand the impact of this toxin on different parts of the brain. In this research, two groups of rats were studied, the 3-AP-treated and the control groups. Behavioral, stereological, and immunohistochemical analyses were performed. The locomotor activity of the 3-AP-treated rats decreased whereas their anxiety levels were higher than in normal controls. Also, memory performance was impaired in animals in the 3-AP group. Microscopic observations showed a decline in the numerical density of neurons in the hippocampus and striatum along with gliosis. Although this toxin is used to affect the ION, it exerts a neurotoxic effect on different brain regions.

Epinephrine injected into the basolateral amygdala affects anxiety-like behavior and memory performance in stressed rats.

The amygdala is known to mediate in moderating the impacts of emotional arousal and stress on memory. According to a growing body of research, the basolateral amygdala (BLA) is an important locus for integrating neuromodulator influences coordinating the retrieval of different types of memory and anxiety. This study aimed to investigate how the epinephrine in the BLA affects hippocampal fear memory, anxiety, and plasticity in control and stressed rats. For four days, male Wistar rats were exposed to electrical foot-shock stress. Animals received bilateral micro-injections of either vehicle or epinephrine (1 µg/side) into the BLA over four days (5 min before foot-shock stress). Behavioral characteristics (fear memory and anxiety-like behavior), histological features and electrophysiological parameters were investigated. Epinephrine injection into BLA resulted in a considerable impairment of fear memory in stressed rats. On the other hand, epinephrine effectively affected fear memory in control rats. Under stress conditions, epinephrine in the BLA is thought to increase anxiety-like behaviors. Treatment with epinephrine significantly increases the slope of fEPSP in the CA1 region of the hippocampus in the control and stress rats. In different groups, foot-shock stress had no effect on the apical and basal dendritic length in the CA1 region of the hippocampus. These results indicate that activating adrenergic receptors diminish fear memory and anxiety-like behaviors in the foot-shock stress, which this impact is independent of CA1 long-term potentiation induction.

Gallic acid ameliorates behavioral dysfunction, oxidative damage, and neuronal loss in the prefrontal cortex and hippocampus in stressed rats.

Gallic acid (GA) is known to be a natural phenolic compound with antioxidant and neuroprotective effects. This study aims to investigate the impact of GA against restraint stress-induced oxidative damage, anxiety-like behavior, neuronal loss, and spatial learning and memory impairment in male Wistar rats. The animals were divided into four groups (n = 8) and subjected to restraint stress for 4 h per day for 14 consecutive days or left undisturbed (control without inducing stress). In the treatment group, the animals were treated with 2 mL normal saline plus 100 mg/kg GA per day for 14 consecutive days (STR + GA group). The animals received the drug or normal saline by gavage 2 h before inducing restraint stress. ELISA assay measured oxidative stress factors. Elevated-plus maze and Morris water maze tests assessed anxiety-like behavior and spatial learning and memory, respectively. Also, neuronal density was determined using Nissl staining. Restraint stress significantly increased MDA and reduced the activities of GPX and SOD in the stressed rats, which were reserved by treatment with 100 mg/kg GA. Restraint stress markedly enhanced the anxiety-like behavior and spatial learning and memory impairment that were reserved by GA. In addition, treatment with GA reduced the neuronal loss in the stressed rats in the hippocampus and prefrontal cortex (PFC) regions. Taken together, our findings suggest that GA has the potential to be used as a good candidate to attenuate neurobehavioral disorders as well as neuronal loss in the hippocampus and PFC induced by restraint stress via reducing oxidative damage.

Effects of the suppression of 5-HT1A receptors in the left, right, or bilateral basolateral amygdala on memory consolidation in chronic stress in male rats.

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.

Biochemical Mechanisms of Beneficial Effects of Beta-Alanine Supplements on Cognition.

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 ß-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.

Creatine supplementation protects spatial memory and long-term potentiation against chronic restraint stress.

Stress contributes to numerous psychopathologies, including memory impairment, and threatens one's well-being. It has been reported that creatine supplementation potentially influences cognitive processing. Hence, in this study, we examined the effects of creatine supplementation on memory, synaptic plasticity, and neuronal arborization in the CA1 region of the hippocampus in rats under chronic restraint stress (CRS). Thirty-two adult male Wistar rats (8 weeks old) weighing 200-250 g were randomly divided into four groups (n = 8/per group): control, stress, creatine, and stress + creatine. CRS was induced for 6 h per day for 14 days, and creatine supplementation was carried out by dissolving creatine (2 g/kg body weight per day) in the animals' drinking water for 14 days. We used the Barnes maze and shuttle box for spatial and passive avoidance memory examination. The in-vivo field potential recording and Golgi-Cox staining were also used to investigate long-term potentiation (LTP) and dendrite arborization in the CA1 pyramidal neurons. Chronic stress impaired spatial memory, dysregulated LTP parameters, and decreased the number of dendrites in the CA1 pyramidal neurons of stressed rats, and creatine supplementation modified these effects in stressed rats. It seems that creatine supplementation can improve spatial memory deficits and synaptic plasticity loss induced by CRS in hippocampal CA1 neurons, possibly by reducing the dendrite arborization damages. However, understanding its mechanism needs further investigation.

Comparative effects of the alcoholic extract of Terminalia chebula and crocin on stress­induced anxiety­like behavior and memory impairment in male rats.

Crocin and Terminalia chebula (T. chebula) were proven to have neuroprotective effects. In this study, we evaluated the preventive effects of crocin and alcoholic extract of the T. chebula alone and in combination to examine their efficacy against chronic restraint stress (CRS)­induced cognitive impairment, anxiety­like behaviors, hippocampal synaptic plasticity deficit as well as neuronal arborization damage in the hippocampal CA1 neurons. Over 14 consecutive days, animals received crocin, T. chebula, or their combination (5 min before CRS). The elevated plus­maze results showed that crocin and T. chebula alone and in combination treatment significantly increased the time spent in open arms, percentage of open arm entries, and head dipping as compared with the CRS group. Barnes maze results showed that administration of crocin and T. chebula alone and their combination significantly improves spatial memory indicators such as distance traveled, latency time to achieving the target hole, and the number of errors when compared to the CRS group. These learning deficits in CRS animals correlated with a reduction of long-term potentiation (LTP) in hippocampal CA1 synapses, which both T. chebula and crocin treatment improved field excitatory postsynaptic potentials (fEPSP) amplitude and fEPSP slope reduction induced by CRS. Golgi­Cox staining showed that T. chebula and crocin treatment increased the number of dendrites and soma arbors in the CA1 neurons compared with the CRS group. Our results suggest that both T. chebula and crocin attenuated CRS­induced anxiety­like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons. We found no significant difference between single treatments of T. chebula or crocin and their combination in protecting CRS­induced anxiety­like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons.

The Complexity of Electroencephalographic Signal Decreases during the Social Stress.

Social stress affects brain function. Trier social stress test (TSST) is a standard test to assess it. The study aimed to analyze the electroencephalographic (EEG) recording during and after TSST in healthy subjects. The EEG signals of 44 healthy men participating in the study were recorded in the control condition, during and after TSST and after 30 min of recovery. Salivary cortisol (SC) and the Emotional Visual Analog Scale (EVAS) score were measured in the control condition, after TSST, and after the recovery period. The false discovery rate correction was used to control the false positive of significance in EEG. In the comparison control condition, the SC and EVAS levels significantly increased after TSST. The relative Delta band frequency significantly increased during TSST. On the other hand, the Beta bands and, in less amount, the Theta and Gamma 1 (30-40 Hz) oscillations decreased, especially in the frontal region. The nonlinear features such as, approximate and spectral entropy, Katz fractal dimension behaved like Beta band oscillation. All changes returned to baseline after TSST except the increase of Katz in the F3 channel after the recovery period. Thus, stress on EEG increased low frequency (1-4 Hz), decreased high frequency (13-40 Hz), and complexity indices during TSST.

Date palm spathe extract reverses chronic stress-induced changes in dendritic arborization in the amygdala and impairment of hippocampal long-term potentiation.

Chronic restraint stress induces anxiety-like behaviors and emotional abnormalities via an alteration of synaptic remodeling in the amygdala and the hippocampus. Given that the date palm spathe has been shown to have neuroprotective effects on different experimental models, this study aimed to address whether the date palm spathe extract (hydroalcoholic extract of date palm spathe [HEDPP]) can reduce chronic restraint stress-induced behavioral, electrophysiological, and morphological changes in the rat model. Thirty-two male Wistar rats (weight 200-220 g) were randomly divided into control, stress, HEDPP, and stress + HEDPP for 14 days. Animals were submitted to restraint stress for 2 h per day for 14 consecutive days. The animals of the HEDPP and stress + HEDPP groups were supplemented with HEDPP (125 mg/kg) during these 14 days, 30 min before being placed in the restraint stress tube. We used passive avoidance, open-field test, and field potential recording to assess emotional memory, anxiety-like behavioral and long-term potentiation in the CA1 region of the hippocampus, respectively. Moreover, Golgi-Cox staining was used to investigate the amygdala neuron dendritic arborization. Results showed that stress induction was associated with behavioral changes (anxiety-like behavioral and emotional memory impairment), and the administration of HEDPP effectively normalized these deficits. HEDPP remarkably amplified the slope and amplitude of mean-field excitatory postsynaptic potentials (fEPSPs) in the CA1 area of the hippocampus in stressed rats. Chronic restraint stress significantly decreased the dendritic arborization in the central and basolateral nucleus of the amygdala neuron. HEDPP suppressed this stress effect in the central nucleus of the amygdala. Our findings indicated that HEDPP administration improves stress-induced learning impairment and memory and anxiety-like behaviors by preventing adverse effects on synaptic plasticity in the hippocampus and amygdala.

Eryngium billardieri extract affects cardiac gene expression of master regulators of cardiomyaopathy in rats with high fatdiet-induced insulin resistance.

BACKGROUND: For years, numerous studies have focused on identifying approaches to increase insulin sensitivity by modifying the signaling factors. In the present study, we examined the effects of Eryngium billardieri extract, as an anti-diabetic herbal medication, on the heart mRNA level of Akt serine/threonine kinase (Akt), mechanistic target of rapamycin kinase (mTOR), peroxisome proliferator-activated receptor gamma (PPARγ), and Forkhead box o1 (Foxo1) in rats with high-fat diet (HFD)-induced insulin resistance (IR). We also assessed the anti-diabetic effects of E. billardieri extract in rats with insulin resistance. METHODS: Twenty-seven male Wistar rats were divided into two groups. Nine rats were fed a normal diet (control group), and 18 rats were fed an HFD for 13 weeks (HFD group). To confirm the induction of insulin resistance, the oral glucose tolerance test (OGTT) was performed and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Then rats with IR were randomly divided into the following groups: the HFD group, which continued an HFD, and the group treated with E. billardieri extract, which received the extract at a concentration of 50 mg/kg for 30 days. On the 30th day, the animals were sacrificed and serum samples were collected for biochemistry analyses. Furthermore, the expression of Akt, mTOR, PPARγ, and Foxo1 was measured in heart tissue using the real-time polymerase chain reaction (PCR) method. RESULTS: Real-time PCR analyses revealed that an HFD can significantly decrease the expression level of Akt, mTOR, and PPARγ in the heart tissue. However, an HFD significantly increased the expression level of Foxo1 in the HFD group compared to the control group (P < 0.05). In addition, our data showed that the administration of E. billardieri extract significantly enhanced the mRNA levels of Akt, PPARγ, and mTOR in the heart tissue compared to the HFD group (P < 0.05), while it significantly decreased the Foxo1 mRNA levels (P < 0.01). CONCLUSION: Given that Akt, mTOR, PPARγ, and Foxo1 are critical factors in insulin resistance, the present study suggests that E. billardieri could probably be used as an alternative treatment for IR as a major feature of metabolic syndrome.

Tarooneh extract relieves anxiety-like behaviors and cognitive deficits by inhibiting synaptic loss in the hippocampus and frontal cortex in rats subjected to chronic restraint stress.

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.

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.

Impact of the covid-19 pandemic on the psychological status and cortisol level of multiple sclerosis patients.

This study aimed to compare the changes in psychological status and cortisol level between multiple sclerosis (MS) patients and a healthy control group (HC). One hundred and fifty-five MS patients and 165 HC subjects had completed questionnaires consisting of 36-Item short health survey (SF-36), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory-II (BDI-II), and fatigue severity score (FSS) before and after (one year from onset) COVID-19 pandemic. The salivary cortisol level was also measured again in 26 MS patients and 14 control individuals. MS patients had lower scores of mental and physical components of quality of life (MCS and PCS), but higher HAM-A, FSS, and BDII scores than HC Before and after COVID-19. There were significant changes in scores of MCS, BDI-II, HAM-A, and FSS after the COVID-19 outbreak in MS patients, but not in PCS score. In HC group, we observed significant changes in scores of MCS, BDI-II, and FSS, but not in scores of PCS and HAM-A. Compared to HC, the MS patients reported greater deterioration in the overall mental health component of their health-related quality of life, and their levels of anxiety and fatigue over the study period. The change of cortisol levels was non-significant with a small effect size.

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.

Analgesic effects of Terminalia chebula extract are mediated by the suppression of the protein expression of nerve growth factor and nuclear factor-κB in the brain and oxidative markers following neuropathic pain in rats.

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.

Irisin/FNDC5 influences myogenic markers on skeletal muscle following high and moderate-intensity exercise training in STZ-diabetic rats.

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.

Multigenerational effects of paternal spatial training are lasting in the F1 and F2 male offspring.

Recent studies on intergenerational transmission of learning and memory performances demonstrated that parental spatial training before fertilization could facilitate learning and memory in the offspring, but many questions remain unclarified. Essential issues regarding whether and how long the effects of parental training in a task can last in several generations, and whether learning a task repeated in the successive generations can enhance a load of multigenerational effects. In the present study, the spatial performances of F1 and F2 generations of male offspring of fathers or grandfathers spatially trained in the Morris Water Maze were evaluated and compared with the performance of a control sample matched for age and sex. Further, to investigate the memory process in F1 and F2 male offspring, brain-derived neurotrophic factor (BDNF), p-ERK1/2 and acetylated histone 3 lysine 14 (H3K14) expression levels in the hippocampus were analyzed. The findings showed that paternal training reduced escape latencies and increased time spent in the target quadrant by F1 and F2 male offspring. Besides, paternal spatial training repeated in two generations did not enhance the beneficial effects on offspring's spatial performances. These findings were supported by neurobiologic data showing that paternal training increased BDNF and p-ERK1/2 in the hippocampus of F1 and F2 male offspring. Furthermore, the hippocampal level of acetylated H3K14 increased in the offspring of spatially trained fathers, reinforcing the hypothesis that the augmented histone acetylation might play an essential role in the inheritance of spatial competence.

A major depressive disorder diagnosis approach based on EEG signals using dictionary learning and functional connectivity features.

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.