Open Field Test Research Articles

Suffruticosol B from Paeonia lactiflora Ameliorates Alzheimer's Disease Pathology by Inhibiting MAO-B Activity.

Monoamine oxidase B (MAO-B) has emerged as a therapeutic target for Alzheimer's disease (AD) due to its involvement in the synthesis of γ-aminobutyric acid (GABA) in reactive astrocytes, which inhibits neuronal activity. Suffruticosol B (Suf-B), isolated from Paeonia lactiflora, is one of the resveratrol oligomers. Although resveratrol oligomers have demonstrated neuroprotective effects, it remains unexplored whether Suf-B exerts therapeutic effects on AD by targeting MAO-B. In this study, we investigated whether Suf-B alleviates AD pathology by mitigating reactive astrogliosis and inhibiting the overproduction of astrocytic GABA. After confirming the MAO-B inhibitory effect of Suf-B through MAO-B enzyme assay, we administered Suf-B to APP/PS1 AD model mice. To test the potential therapeutic action of Suf-B in AD, a series of experiments were conducted, including behavioral tests such as the open field test, novel object recognition test, Barnes maze test, passive avoidance test, as well as immunohistochemistry and whole-cell patch-clamp recordings. We found that Suf-B markedly inhibited MAO-B activity without causing cytotoxicity. Immunohistochemistry and electrophysiology experiments demonstrated that Suf-B significantly reduced astrocyte reactivity, as well as an aberrant increase in GABA production and tonic GABA release from astrocytes in AD. Behavior test results indicated that Suf-B treatment restored cognitive function in APP/PS1 mice. In conclusion, Suf-B effectively reduces excessive GABA production in reactive astrocytes by inhibiting MAO-B, normalizing aberrant inhibition in hippocampal neurons in an AD mouse model. These results suggest that Suf-B has potential as a treatment for AD and may be applicable to other brain diseases associated with reactive astrogliosis.

A reinvestigation of cognitive styles in sticklebacks: decision success varies with behavioral type

Abstract The ‘cognitive styles’ hypothesis suggests that individual differences in behavior are associated with variation in cognitive performance via underlying speed-accuracy trade-offs. While this is supported, in part, by a growing body of evidence, some studies did not find the expected relationships between behavioral type and cognitive performance. In some cases, this may reflect methodological limitations rather than the absence of a true relationship. The physical design of the testing arena and the number of choices offered in an assay can hinder our ability to detect inter-individual differences in cognitive performance. Here, we re-investigated the cognitive styles hypothesis in threespine stickleback (Gasterosteus aculeatus), adapting the maze design of a previous study which found no cost to decision success by faster (bolder) individuals. We used a similar design but increased the size of the maze and incorporated an additional choice in the form of a third maze arm. We found, in accordance with cognitive style expectations, that individuals that were consistently slower to emerge from the start chamber made fewer errors than fish that emerged faster. Activity in an open field test, however, did not show evidence of a relationship with decision success, possibly due to the low number of repeated observations per fish in this separate assay. Our results provide further empirical support for the cognitive styles hypothesis and highlight important methodological aspects to consider in studies of inter-individual differences in cognition.

Anti-neuropathic effects of astaxanthin in a rat model of chronic constriction injury: passing through opioid/benzodiazepine receptors and relevance to its antioxidant and anti-inflammatory effects

IntroductionNeuropathic pain is a debilitating neurological disorder and is on the rise. Since no effective treatment has been so far approved to combat the complex pathological mechanisms behind neuropathic pain, finding new therapeutic candidates is of great importance. Astaxanthin (AST) is a carotenoid with strong antioxidant, and anti-inflammatory activities.PurposeThe present research aimed to evaluate the ameliorative effects of AST on a rat model of neuropathic pain.MethodsTo induce neuropathic pain, a chronic constriction injury (CCI) model was employed. Accordingly, Wistar rats were divided into nine groups of six including sham, negative control group (CCI), positive control group gabapentin (100 mg/kg), AST (5, 10 mg/kg), flumazenil (0.5 mg/kg), naloxone (0.1 mg/kg), AST (10 mg/kg) + flumazenil (0.5 mg/kg), and AST (10 mg/kg) + naloxone (0.1 mg/kg) were administered intraperitoneally on days 1, 3, 5, 7, 10, and 14. To check the experimental signs of neuropathic pain and motor dysfunction, hot plate, acetone drop, and open field tests were used at the same time points. Additionally, biochemical assay and zymography were done on days 7 and 14 to assess the changes in catalase, glutathione and nitrite, as well as matrix metalloproteinases (MMP-2 and MMP-9). Besides, histological evaluations were performed for tissue damages on days 7 and 14.Results and discussionResults indicated that intraperitoneal injection of AST improved allodynia, hyperalgesia, and locomotor activity after CCI. AST also increased catalase and glutathione while suppressing nitrite, MMP-2, and MMP-9 activity through opioid/benzodiazepine receptors.ConclusionThe results highlighted AST as a promising candidate against neuropathic pain with beneficial effects on motor function by suppressing inflammatory mediators, and augmenting antioxidant factors, passing through opioid/benzodiazepine receptors.

Semen Cuscutae flavonoids activated the cAMP-PKA-CREB-BDNF pathway and exerted an antidepressant effect in mice

BackgroundSemen Cuscutae flavonoids (SCFs) constitute a class of metabolites of Semen Cuscutae, a botanical drug that was recently found to have an anti-depression effect. This study aimed to evaluate the anti-depression effects of SCFs in chronic unpredictable mild stress (CUMS)-induced mice and to interrogate the underlying mechanisms.Materials and methodsThe CUMS mice were used for assessing the effects of SCFs treatments on depression. Mice were randomly divided into five groups. Four groups were subjected to the CUMS induction and concomitantly administered orally with either the vehicle or with a high-, medium-, and low-dose of SCFs, once per day for 4 weeks. One group was kept untreated as a control. The mice were then assessed for their statuses of a number of depression-related parameters, including body weight, food intake, sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swim test (FST). In addition, a day after the completion of these tests, biopsies from the hippocampus were harvested and used to perform metabolomics by HPLC-MS/MS and to assess the levels of cAMP by ELISA and the levels of PKA, CREB, p-CREB, and BDNF by Western blot analyses.ResultsSCFs resulted in significant increases in both body weight and food intake and in the amelioration of the depressive-like behaviors in CUMS mice. A high-dose SCFs treatment led to significant alterations in 72 metabolites, of which 26 were identified as potential biomarkers for the SCFs treatment. These metabolites are associated with lipid, amino acid, and nucleotide metabolism. Among 26 metabolites, cAMP was positively correlated with body weight, SPT, OFT-total distance, and OFT-central residence time, while negatively correlated with immobility time in TST and FST, linking a change in cAMP with the SCFs treatment and the significant improvement in depressive symptoms in CUMS mice. Further analyses revealed that the levels of cAMP, PKA, CREB, p-CREB, and BDNF were reduced in the hippocampus of CUMS mice but were all increased following the SCFs treatments.ConclusionSCFs could ameliorate hippocampal metabolic disturbances and depressive behaviors and cause the activation of the cAMP-PKA-CREB-BDNF signaling pathway in the hippocampus of CUMS mice.

Tracking puppy development: automated analysis and qualitative behavioral assessmentin repeated open field tests.

Early puppy development is a crucial period that significantly influences a dog's lifelong health, behavior and personality. In this study, the behavioral development of Kangal puppies was investigated through repeated open-field testing, focusing on exploratory behavior, mobility, and responses to novel stimuli. Thirty-three Kangal puppies (20 males and 13 females) from various breeding centers in Sivas Province, Türkiye, were evaluated. The puppies were tested in a controlled open-field environment at 5, 6, and 8 weeks of age. Tests included a novel environment test at 5 weeks and novel object tests at 6 and 8 weeks. Mobility rate, exploration rate, and total distance parameters were measured using automated tracking software (ToxTrac). Qualitative behavioral assessments (QBAs) were performed to evaluate three distinct behavioral and emotional aspects: curiosity, comfort, and fearfulness. The results of these assessments revealed significant increases in curiosity and comfort scores over the testing weeks, with a concomitant decrease in fearfulness. Additionally, tracking data showed increased mobility and decreased exploration rates throughout the testing weeks. Significant correlations were found between curiosity and exploratory behavior, as well as between mobility and comfort scores. Overall, our findings suggest that Kangal puppies exhibit expected behavioral developments in repeated open field testing, with patterns consistent across multiple analyses. These results provide valuable insights into the behavioral development of Kangal puppies and underscore the importance of considering curiosity and other internal motivations in understanding animal behavior.

PKR downregulation prevents copper-induced synaptic dysfunction and cognitive impairment in a murine model of Wilson’s disease

Synaptic efficacy is critical for memory formation and consolidation. Accumulating evidence suggest that synapses are impaired during Wilson’s disease (WD), contributing to neuronal dysfunction and cognitive decline. WD is a prototypical condition among the copper metabolism disorders. Cognitive impairment is a common feature of affected patients with neurological symptoms, presenting as memory deficits, decreased cognitive flexibility, and impaired learning capabilities. These cognitive deficits can significantly impact the quality of life, affecting work and academic performance. However, the mechanisms mediating the inhibitory synaptic dysfunction in WD are incompletely understood. We investigated the effects of the double-stranded RNA-dependent protein kinase/eukaryotic initiation factor 2α (PKR/eIF2α) pathway on synaptic structure and function in WD using a murine model, toxic milk (TX mice). During mouse open-field tests, we noted a substantial rise in the mobility/immobility ratio among WD model animals compared to that in WT mice. Additionally, WD mice exhibited diminished central area exploration, as evidenced by reduced travel distance. Moreover, they displayed prolonged escape latency in the Barnes maze, suggesting that chronic copper accumulation is associated with neuropsychiatric alterations and cognitive impairment. We also found a decrease in the expression of synapse-associated proteins (synapsin 1, synaptophysin, postsynaptic density protein-93 [PSD93], postsynaptic density protein-95 [PSD95]), and vesicle-associated membrane protein2 [VAMP2]) besides abnormal neurotransmitter levels (including glutamate and GABA), indicating the presence of synaptic dysfunction in TX mice. Inhibiting PKR via C16 prevented these changes, suggesting that dysfunctional cognition is associated with the PKR/eIF2α pathway. We also observed changes in synapses, vesicles, dendritic spine density, and dendritic length that were associated with the presence of cognitive dysfunction. Further investigation revealed that C16 treatment decreased the TUNEL-positive cell numbers in the hippocampus of TX mice and prevented 8-OHdG-induced synaptic dysfunction. Results suggest that PKR downregulation prevents copper-induced synaptic dysfunction in the murine WD model. Therefore, targeting PKR pharmacologically may be a potential therapeutic strategy for treating the copper-induced neuropathology of patients with WD.

The primary studies of epigallocatechin-3-gallate in improving brain injury induced by chronic high-altitude natural environment in rats by 7.0T high-field MR imaging

BackgroundEpigallocatechin-3-gallate (EGCG) is one of the most abundant and important bioactive polyphenolic compounds in green tea. However, despite its potent antioxidant effects, its neuroprotective effects on chronic high altitude (HA)-induced nerve damage have not been reported. The purpose of this study is to use quantitative susceptibility mapping (QSM) with pathology to dynamically evaluate the status of brain damage and the effect of EGCG. MethodsA model of HA environments-induced brain injury was established of Sprague-Dawley (SD) rats in a natural plateau environment for 4 weeks, 8 weeks, 12 weeks and 20 weeks. Behavioral alterations were then observed and assessed with the open field test (OFT) and Morris water maze (MWM) test. The microglial activation, nissl staining and neural degeneration by Fluoro Jade B in the hippocampus of the rats were observed by immunohistochemistry. In the rats, serum erythropoietin (EPO), hippocampal inflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]), ferritin, oxidative stress (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT] and malondialdehyde [MDA]) were detected using ELISA kits and biochemical methods. Iron accumulation was observed by QSM and colorimetry. Iron metabolisms (ceruloplasmin [Cp], transferrin [Tf], divalent metal transport1 [DMT1] and hepcidin [Hep]) were detected using qPCR. Neural ultrastructural changes were evaluated with electron microscope. Salidroside treatment was chosen as the positive control group in ELISA, biochemical detection and electron microscopy. ResultsThe susceptibility values in the left and right hippocampus, the hippocampal ferritin, serum and hippocampal iron content increased significantly after HA exposure. The expression of hippocampal Cp and Hep decreased and the expression of Tf increased. Nissl staining revealed that the neurons of hippocampal CA1 region of h-20w group were small and irregular, atrophied, and nuclear shrinkage. Tissue oxidative stress and inflammatory indicators (MDA, TNF-α, IL-1β, IL-6) increased while antioxidant enzymes (SOD, CAT, GSH-Px) decreased. EGCG attenuated HA environments-induced cognitive impairment, iron accumulation, microglial activation and neural degeneration. The effects of EGCG in reducing EPO and the metal chelating property with respect to iron were dose-dependent, with effects of EGCG (50 mg/kg) being similar to those of salidroside (50 mg/kg). ConclusionsEGCG can act as a neuroprotective agent against chronic HA environments-mediated neural injuries. QSM provides a potential complementary imaging technique to detect the effect of treating HA diseases.

Tim-3 Deficiency Ameliorates Motor Deficits and Neuroinflammation in MPP+/MPTP-Induced Parkinson's Disease Models via the NF-κB/NLRP3 Pathway.

Parkinson's disease (PD) is a common neurodegenerative disorder, and neuroinflammation plays a pivotal role in its pathogenesis. T-cell immunoglobulin and mucin-domain-containing molecule 3 (Tim-3) is a crucial immunoregulatory mediator in various diseases; however, its roles and underlying molecular mechanisms in PD remain unclear. We established in vitro and in vivo 1-methyl-4-phenylpyridinium (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD models in Tim-3-knockout BV2 cells and mice, respectively. Motor function was assessed through behavioral tests, including pole, traction, forced swimming, and open field tests. Immunofluorescence was used to examine dopaminergic neuron loss and glial activation. The expression levels of nuclear factor-kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) pathway components were evaluated by western blotting. Proinflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). Compared with the wild-type, Tim-3 expression was significantly increased in the PD model, and Tim-3 deficiency mitigated MPTP-induced motor deficits, dopaminergic neuron loss, and glial cell activation. Furthermore, Tim-3 deficiency suppressed neuroinflammation by negatively modulating the NF-κB/NLRP3 pathway, thereby downregulating the expression of the proinflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α. These findings indicate that Tim-3 plays a proinflammatory role in PD by regulating the NF-κB/NLRP3 pathway, highlighting Tim-3 as a promising therapeutic target for PD.

'The effect of neuropeptide Y1 receptor agonist on hypothalamic neurogenesis in rat experimental depression model'.

Depression is responsible for neuropathies such as decreased neurogenesis and increased dendritic atrophy. There is information that antidepressant treatments have an effect by increasing hippocampal neurogenesis and neurotrophic factor expression. The neuropeptide Y1 (NPY1R) receptor agonist has been suggested to have anxiolytic effects. Based on this information, it was aimed to investigate the effect of NPY1R agonist on depression in rats with depression using the CMS model and to determine how depression affects cell proliferation in the hypothalamus and hypothalamic peptide levels. Forty-eight adult, male Wistar albino rats were divided into groups as Control, Depression (D), Depression + NPY1R and NPY1R. Various stressors were applied to D for 30 days. An open field test (OFT) and forced swim test (FST) were performed to check whether the animals were depressed. On the 16th day, an osmotic mini pump was placed under the skin and NPY1R (130 ul/kg/day) was applied for 15 days. Behavioral tests were performed, hypothalamic peptide gene expression levels were analyzed by quantitative RT-PCR and statistical evaluations were made using ANOVA. A decrease in the percentage of movement in the D and control groups were noted in the OFT, an increase in the immobility time in the D group in the FST, and an increase in swimming behavior in the DNPY1R group. The animals did not display any anxiety behavior based on the elevated plus maze test results. It caused a decrease in IGF1R, FGF2, POMC, NPY and GLUT2 gene expression in the hypothalamus of depression group animals, and an increase in NPY gene expression in NPY1R treatment. This study compellingly demonstrated that exposure to chronic mild stress simultaneously downregulates gene expression in the hypothalamus; we observed that NPY receptor NPY1R treatment increased the effect of NPY. Therefore, adjunctive treatments with appropriate molecules such as NPY, Y1 receptor agonists or pharmacological derivatives may have significant potential in the treatment of depression.

Effects of Black Rice Anthocyanin Extract on Depression-Like Behavior in Chronic Unpredictable Mild Stress Model Mice

Objective: To investigate the effects of black rice anthocyanins extract (BSE) on depression-like behavior in mice with chronic unpredictable mild stress (CUMS). Methods: A total of 30 male Kunming mice were randomly divided into Control group, model group (CUMS) and black rice anthocyanin extract group (300 mg/kg). Except the blank group, all mice were treated with CUMS to induce depression. After 21 days of intragastric administration, the behavioral changes of the mice were analyzed by body weight, sucrose preference test, open field test, and water maze test. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Hematoxylin-eosin staining (HE) was used to observe the pathological changes of neurons in hippocampal CA1 and CA3 regions. Cell apoptosis in hippocampus was detected by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling (TUNEL) staining. Results: Compared with the model group, the brown-rice anthocyanin treatment group showed significantly increased sucrose preference, increased horizontal movement distance and vertical standing times in the open field test, decreased escape latency in the water maze test, increased residence time in the target quadrant and the number of crossing the platform, and alleviated the damage of hippocampal neurons. Plasma ACTH, CORT, and CRH levels were decreased, and apoptosis rates in the hippocampus were decreased. Conclusion: Black rice anthocyanins have a significant antidepressant effect possibly by regulating the function of HPA axis.

Neuronal plasticity changes in the central amygdala and prelimbic cortex network in mice with chronic unpredictable mild stress-induced depression

To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors. C57Thy1-YFP/GAD67-GFP mice were randomized into control group (with no treatment) and chronic unpredictable mild stress (CUMS) group (n=15) subjected to CUMS for 8 weeks. Depression-like behaviors of the mice were assessed using sucrose preference test, open field test, and forced swimming test, and their spatial learning and memory abilities were evaluated using Morris water maze test. The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala (CeA) and the prelimbic cortex (PrL) using whole-cell patch-clamp technique. Compared with the control mice, CUMS mice showed significantly decreased sucrose preference, total distance moved, number of grid-crossings, entries into the central area, and time spent in the central area in the open field test (P < 0.01). In the forced swimming test, CUMS mice exhibited obviously shortened time of struggling, swimming, and climbing with increased immobility time. In Morris water maze test, CUMS mice showed significantly increased escape latency and path length, decreased percentage of distance and swimming time within the target quadrant, and increased first entry latency into the target zone and swimming time within the opposite quadrant. Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL, while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL. CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

Environmental enrichment reduces adgrl3.1-Related anxiety and attention deficits but not impulsivity

Environmental factors play a role in the development and severity of neuropsychiatric disorders. Externalizing disorders are characterized by disruptive, impulsive, and often aggressive behaviors, including difficulties with self-control, rule-breaking, and a tendency to act out in ways that may harm oneself or others. Externalizing disorders frequently co-occur with internalizing disorders, such as anxiety. Individuals experiencing both externalizing/internalizing disorders are often among the most likely to seek healthcare services, as this co-occurrence is associated with more severe symptomatology and greater functional impairment. Here, we investigated the impact of environmental enrichment (EE) on adgrl3.1, a gene associated with impulsivity and attention deficits in zebrafish (Danio rerio). This gene encodes a receptor involved in cell adhesion and signaling and has been linked to susceptibility to externalizing disorders. Zebrafish were reared in either standard or enriched environments (from 15 days-post fertilization), and attention, impulsivity, and anxiety-related phenotypes were assessed at adult stages (4 months-post fertilization) using the open field test and a 5-choice serial reaction time task. EE mitigated anxiety-related behaviors in adgrl3.1 knockouts, normalizing locomotor patterns and decreasing thigmotaxis. Although attention deficits were reduced in adgrl3.1-/- fish reared in EE, impulsive behaviors were not. Together, these findings suggest that while environmental enrichment (EE) mitigates externalizing and internalizing symptoms in adgrl3.1 mutants, impulsivity remains less responsive to EE used in this study, indicating its distinct resistance to modulation.

Unpredictable mild stress accelerates the emergence of motor deficits in a rat model of progressive parkinsonism

Parkinson&amp;rsquo;s disease (PD) is a multifactorial condition associated with genetic and environmental factors. In recent years, the role of chronic psychophysiological stress as a predisposing factor for PD is gaining increasing attention. Clinical and experimental evidence indicates that chronic stress exerts adverse effects on the brain. Nevertheless, the potential role of chronic stress in the predisposition to PD remains poorly understood. This study aimed to investigate the effects of exposure to a chronic unpredictable mild stress (UMS) protocol on the onset of parkinsonism in Wistar rats repeatedly treated with a low dose of reserpine. Wistar rats were either exposed to UMS for 1 week or not exposed (control group). Then, the animals were repeatedly treated with a low dose of reserpine or vehicle every other day for 20 days. Behavioral motor evaluations were conducted using catalepsy and open field tests. Moreover, plasma corticosterone (CORT) levels and lipid peroxidation were evaluated. As expected, the UMS protocol increased plasma CORT levels, and reserpine treatment led to a progressive enhancement of cataleptic behavior. Animals exposed to UMS and treated with reserpine exhibited motor alteration earlier during the protocol. No differences were observed in oxidative stress between experimental and control groups, as evaluated through lipid peroxidation assay. Our results showed that chronic mild stress accelerated the onset of motor deficits in reserpine-treated animals.

The overexpression of eIF4E decreases oxytocin levels and induces social-cognitive behavioral disorders in mice.

Overexpression of the eukaryotic initiation factor 4E (eIF4E) gene has been associated with excessive stereotypic behaviors and reduced sociability, which manifest as autism-like social cognitive deficits. However, the precise mechanisms by which eIF4E overexpression induces insufficiently these autism-like behaviors and the specific brain regions implicated remain insufficiently understood . Oxytocin, a neurotransmitter known for its role in social behavior, has been proposed to modulate certain autism-related symptoms by influencing microglial function and attenuating neuroinflammation. Nonetheless , the contributions of the hippocampus and oxytocin in the content of eIF4E overexpression-induced autistic behaviors remain elucidated . To investigate this issue,esearchers utilized the three-chamber social interaction test, the open field test, and the Morris water maze to evaluate the social cognitive behaviors of the two groups of mice. Additionally, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, Western blotting, and RT-qPCR were employed to quantify oxytocin levels and assess hippocampal microglial activation.The results indicate that overexpression of eIF4E in mice is associated with significant impairments in social cognition, alongside pronounced marked hyperactivation of hippocampal microglia.Significance statement Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental disorders characterized by social cognitive impairment.Research has indicated a correlation between the overexpression of the eukaryotic initiation factor 4E (eIF4E) gene and autism-like social cognitive impairment.Oxytocin (OXT), a neurotransmitter, plays a role in regulating hippocampal microglial activity and attenuating neuroinflammation. This modulation may impact social cognition in individuals with autism.Nevertheless,it remains unclear whether there is an involvement of the hippocampus and oxytocin in autism-like social cognitive impairments due to eIF4E overexpression. The present study suggests that overexpression of eIF4E may induce hyperactivation of microglia and contribute to social cognitive impairment by decreasing oxytocin levels in the hippocampus.These findings offer molecular insights into the manifestation of autism-like behavior resulting from eIF4E overexpression and may guide future clinical interventions.

Phytochemical characterization, toxicity and pharmacological profile of the central effects of the fixed fruit pulp oil of Mauritia flexuosa L.F. (buriti)

Anxiety and depression are mental disorders that have been exponentially increasing over the last decades. Psychopharmacology emerged to try to alleviate the symptoms of these disorders; however, the side effects and the time it takes to achieve the desired effect are factors that decrease the search for and adherence to treatment. To remedy this situation, new compounds capable of improving the performance of these medications and reducing their adverse effects have been sought. The use of medicinal plants has been widely employed for this purpose. Mauritia flexuosa F.L., a palm tree with high incidence in Brazil, has been heavily targeted as all its parts are usable. The objective of this study is to evaluate the effects of fixed oil from the fruit of the buriti palm in models of depression and anxiety. The phytochemical profile of this oil and its toxicity were also investigated. The experiments conducted included the open field, rotarod, forced swim, and elevated plus maze tests. As a result, it was observed that the fixed oil from buriti palm presented 18 compounds, with elaidic acid being the major one, and showed no signs of toxicity. However, it demonstrated a possible stimulating activity in the open field test and had no effect on the motor system in the rotarod test. Furthermore, it exhibited an antidepressant-like effect in the forced swim test but an anxiety-like effect in the elevated plus maze test. Therefore, buriti oil may potentially be used in new formulations to assist in the treatment of anxiety and depression.

Exploring the anti-depressant effects and nitric oxide modulation of quercetin: A preclinical study in Socially Isolated mice

Objectives This study investigates the effects of quercetin, an antioxidant and nitric oxide (NO) modulator, on depressive-like behaviours triggered by social isolation stress (SIS) in mice. SIS, known to harm psychosocial functioning and increase the risk of depression, involves oxidative stress and NO in its pathophysiology. Methods 72 male mice were divided into nine groups, including the social (SC) group as the control group (stress-free with normal saline intake). The isolation (IC) groups received normal saline, quercetin at doses of 10, 20, and 40 mg/kg, the nitric oxide synthetase inhibitor L-NAME at a dose of 5 mg/kg, the NO precursor L-arginine at a dose of 100 mg/kg, an ineffective dose of quercetin combined with L-NAME and an effective dose of quercetin combined with L-arginine. Behavioural tests (open-field, forced swimming, and splash tests) were conducted, followed by measuring hippocampal nitrite levels. Results Quercetin significantly reduced immobility in the forced swimming test, increased activity in the open-field test, and enhanced grooming behaviour, particularly at 40 mg/kg. Co-administration of an ineffective dose of quercetin (10 mg/kg) with L-NAME increased immobility and grooming activity time. Interestingly, co-administration of the effective dose of quercetin (40 mg/kg) with L-arginine increased immobility time in the FST. Additionally, administration of quercetin at doses of 20 and 40 mg/kg significantly reduced the nitrite level in the hippocampus of SIS mice. Furthermore, co-administration of L-NAME and L-arginine with ineffective and effective doses of quercetin decreased and increased nitrite levels in the hippocampus and increased immobility time in the FST compared to their respective counterparts administered alone. Conclusions These results suggest quercetin’s potential in alleviating depression by modulating NO levels, pointing to its promise in treating depression associated with chronic stressors like social isolation.

High-gamma frequency flash stimulation as a possible cognitive facilitator in rat pups

High-gamma frequency flashes can enhance cognition by synchronizing neural oscillations in mammals. Early flash treatment promotes the development of improved cognitive functions in young children. However, it is unclear whether exposure to high-gamma frequency flashes in preschool-aged individuals affects cognition in preadolescents by regulating neural oscillations in the brain. Here, we aimed to investigate the effects of gamma-frequency flashes on cognitive ability. In this study, the effect of high-frequency flicker on cognitive performance was verified by behavioural experiments such as the open-field test and the water maze, but also proteomics. We found that external 40 Hz and 70 Hz frequency flashes synchronized neural oscillations at the corresponding frequencies in the primary visual cortex (V1) of rats. Rats that underwent 70 Hz flash intervention had better cognitive behavioural performance in the early stages of training. The 70 Hz flash frequency upregulated proteins associated with neuronal growth and differentiation, such as Snapin, FoxO3, Hspa12a, and Penk, and activated the MAPK signalling pathway, signalling pathway regulating stem cell pluripotency, and the neuroactive ligand-receptor interaction pathway. These proteins and pathways play important roles in cognitive functions. Our study revealed that 70 Hz flashes received by young children early in their development substantially promote the growth of cognitive capabilities in the brain. Exposure to 70 Hz flashes may be a new intervention method and a new strategy for improving cognition.

Antidepressant and anxiolytic effects of Wuling Capsule in CSDS mice: Alleviating HPA axis hyperactivity via the Nesfatin-1/NF-κB signaling pathway

Ethnopharmacological relevanceWuling capsule, composed of the traditional Chinese medicine Wuling mycelia powder, is made by fermenting and processing Xylaria nigripes (Kl.) Sacc. Clinically, it is commonly used to alleviate depression and anxiety. However, the mechanisms through which Wuling capsule exerts its therapeutic benefits have not been clearly defined. Aim of the studyThis study aims to elucidate the mechanisms by which Wuling capsule alleviates depression and anxiety like behaviors induced by chronic social defeat stress (CSDS) in mice. Materials and methodsHigh-performance liquid chromatography-tandem mass spectrometry system was used to identify the components of the Wuling capsule. Mice were subjected to CSDS to induce depression and anxiety-like behaviors. The expression of hypothalamic corticotropin-releasing hormone (CRH) and Nesfatin-1, as well as serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. Behavioral assessments included the open field test, elevated plus maze, sucrose preference test, and forced swim test to evaluate depression and anxiety levels. Specific manipulation of Nesfatin-1 in the paraventricular nucleus of the hypothalamus (PVN) or cells was achieved through stereotaxic virus injection or plasmid transfection. Intracerebral cannula implantation was used for PVN-specific drug administration. ResultsA total of 123 different components were identified in Wuling capsule. CSDS induced depression and anxiety-like behaviors in mice, along with hyperactivation of the HPA axis, increased hypothalamic Nesfatin-1 levels, and elevated nuclear factor kappa-B (NF-κB) phosphorylation. Overexpression of Nesfatin-1 in the hypothalamus mimicked the effects of CSDS. Conversely, knockdown of hypothalamic Nesfatin-1 or PVN-specific administration of Nesfatin-1 antibody or NF-κB antagonist mitigated CSDS-induced depression and anxiety-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. In neuroblastoma-2a (N2a) cells, overexpression of Nesfatin-1 led to increased NF-κB phosphorylation and CRH levels, whereas knockdown of Nesfatin-1 produced the opposite effects. Treatment with Wuling capsule alleviated CSDS-induced depression and anxiety-like behaviors, HPA axis hyperactivity, and activation of the hypothalamic Nesfatin-1/NF-κB pathway. ConclusionsThe hypothalamic Nesfatin-1/NF-κB pathway plays a significant role in depression by modulating the HPA axis and is involved in the antidepressant and anxiolytic effects of Wuling capsule.

Transplanted deep-layer cortical neuroblasts integrate into host neural circuits and alleviate motor defects in hypoxic-ischemic encephalopathy injured mice

BackgroundHypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although intensive studies and therapeutic approaches, there are limited restorative treatments till now. Human embryonic stem cell (hESCs)-derived cortical neural progenitors have shown great potentials in ischemic stroke in adult brain. However, it is unclear whether they are feasible for cortical reconstruction in immature brain with hypoxic-ischemic encephalopathy.MethodsBy using embryonic body (EB) neural differentiation method combined with DAPT pre-treatment and quantitative cell transplantation, human cortical neuroblasts were obtained and transplanted into the cortex of hypoxic-ischemic injured brain with different dosages 2 weeks after surgery. Then, immunostaining, whole-cell patch clamp recordings and behavioral testing were applied to explore the graft survival and proliferation, fate commitment of cortical neuroblasts in vitro, neural circuit reconstruction and the therapeutic effects of cortical neuroblasts in HIE brain.ResultsTransplantation of human cortical neural progenitor cells (hCNPs) in HIE-injured cortex exhibited long-term graft overgrowth. DAPT pre-treatment successfully synchronized hCNPs from different developmental stages (day 17, day 21, day 28) to deep layer cortical neuroblasts which survived well in HIE injured brain and greatly prevented graft overgrowth after transplantation. Importantly, the cortical neuroblasts primarily differentiated into deep-layer cortical neurons and extended long axons to their projection targets, such as the cortex, striatum, thalamus, and internal capsule in both ipsilateral and contralateral HIE-injured brain. The transplanted cortical neurons established synapses with host cortical neurons and exhibited spontaneous excitatory or inhibitory post-synaptic currents (sEPSCs or sIPSCs) five months post-transplantation. Rotarod and open field tests showed greatly improved animal behavior by intra-cortex transplantation of deep layer cortical neuroblasts in HIE injured brain.ConclusionsTransplanted hESCs derived cortical neuroblasts survive, project to endogenous targets, and integrate into host cortical neural circuits to rescue animal behavior in the HIE-injured brain without graft overgrowth, providing a novel and safe cell replacement strategy for the future treatment of HIE.

In vivo Protection of Vitamin K in NMDA-Induced Memory Impairment

Background: Stimulation of N-Methyl-D-aspartate (NMDA) receptors with a neurotoxic dose of NMDA is commonly used to model certain characteristics of neurodegenerative disorders. A neurotoxic dose of NMDA injected into the CA1 region of the hippocampus causes excitotoxic damage and likely leads to memory impairment. Objectives: This study aimed to assess the effect of NMDA on passive avoidance learning and open-field tests in male rats, both with and without vitamin K (Vit K), to explore Vit K's potential neuroprotective properties. Methods: Passive avoidance learning and open-field tests were conducted to assess recognition memory. In both tests, a retention session was held 24 hours post-training. N-Methyl-D-aspartate (20 µg/µL) was administered via cannula, and Vit K (10 mg/kg, s.c.) was given daily for 30 days into the CA1 region. Results: N-Methyl-D-aspartate administration reduced step-through latency (STL) and increased time spent in the dark compartment (TDC) during retention sessions. It also decreased locomotor activity and rearing behavior in open-field tests. In contrast, Vit K increased STL and decreased TDC in NMDA-treated rats, with observed improvements in locomotor activity and rearing behavior. Conclusions: N-Methyl-D-aspartate administration in the CA1 region induced memory deficits in passive avoidance and open-field tests. The findings suggest that Vit K may exert neuroprotective effects against NMDA-induced excitotoxic neuronal damage, potentially improving memory impairments.