Splash Test Research Articles

Depressive-like behavior and cognitive impairment induced by acute administration of dexamethasone: Pharmacological effects of 2-phenyl-3-(phenylselanyl)benzofuran in female Swiss mice

Synthetic glucocorticoid administration has been reported to play a role in depression and cognitive decline. The present study investigated the 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1) effects against the depressive-like behavior, memory impairment, and neurochemical alterations caused by acute dexamethasone administration in female Swiss mice. A dexamethasone dose-response curve (0.07–0.5 mg/kg, subcutaneous route, s.c.) was initially performed to validate the depressive-like behavior induction, in which the 0.25 mg/kg dose was more effective. Two experimental sets were performed to test the SeBZF1 (5 and 50 mg/kg, intragastric route, i.g.) pharmacological effect in this animal model. The 1st set revealed that the SeBZF1 reverses the dexamethasone-induced depressive-like behavior in the tail suspension test and in the splash test. In the 2nd experimental set, the compound effects of reversing the depressive-like behavior in the forced swimming test and the memory deficit in the Y-maze test induced by acute treatment with dexamethasone were demonstrated. Furthermore, SeBZF1 reversed the increase in the monoamine oxidase (MAO) activity in the prefrontal cortex (isoforms A and B) and in the hypothalamus (isoform A) caused by dexamethasone. However, no changes were observed in hippocampal MAO activity. Furthermore, animals treated with dexamethasone and SeBZF1 demonstrated a partially lower acetylcholinesterase activity in the prefrontal cortex compared with the induced group. In summary, the present study demonstrated that SeBZF1 reverses depressive-like behavior and memory deficits caused by acute dexamethasone treatment in female Swiss mice. Possibly the compound exerts its antidepressant-like action by increasing the availability of monoamines, while its effects on memory are still partially understood.

Postweaning cafeteria diet induces a short-term metabolic disfunction and a differential vulnerability to develop anxiety-like and depressive-like behaviors in male but not female rats.

Children and adolescents are high consumers of Western diets (rich in fat and sugars), which is a risk factor for overweight and obesity. Moreover, the presence of anxiety and depression among this population has increased significantly. This study explores in young postweaning rats the association between Western diet consumption and the development of metabolic and behavioral disturbances. At postnatal day (PN) 24,Wistarratsof both sexes were weaned and assigned to a control or cafeteria diet (CAF) group. After short-term exposure, a group of rats was euthanized at PN31 to obtain abdominal fat pads and blood samples. Another group of rats was tested in the open-field test, splash test, anhedonia test, and social play across 11days (PN32-42). The CAF groups exhibited a significantly high level of body fat, serum glucose, triglycerides, leptin, and HOMA index when compared to the control groups. Only CAF males exhibited anxiety-like and depression-like behavior. Present results indicate that postweaning short-term exposure to a CAF diet has immediate detrimental effects on metabolism in both sexes. However, only CAF males showed mood disturbances. This study provides evidence that a CAF diet exerts immediate effects on behavior and metabolism in the postweaning period and that sexes present differential vulnerability.

Komagataella pastoris KM71H Mitigates Depressive-Like Phenotype, Preserving Intestinal Barrier Integrity and Modulating the Gut Microbiota in Mice

The role of intestinal microbiota in the genesis of mental health has received considerable attention in recent years, given that probiotics are considered promising therapeutic agents against major depressive disorder. Komagataella pastoris KM71H is a yeast with probiotic properties and antidepressant-like effects in animal models of depression. Hence, we evaluated the antidepressant-like effects of K. pastoris KM71H in a model of antibiotic-induced intestinal dysbiosis in male Swiss mice. The mice received clindamycin (200 μg, intraperitoneal) and, after 24 h, were treated with K. pastoris KM71H at a dose of 8 log CFU/animal by intragastric administration (ig) or PBS (vehicle, ig) for 14 consecutive days. Afterward, the animals were subjected to behavioral tests and biochemical analyses. Our results showed that K. pastoris KM71H administration decreased the immobility time in the tail suspension test and increased grooming activity duration in the splash test in antibiotic-treated mice, thereby characterizing its antidepressant-like effect. We observed that these effects of K. pastoris KM71H were accompanied by the modulation of the intestinal microbiota, preservation of intestinal barrier integrity, and restoration of the mRNA levels of occludin, zonula occludens-1, zonula occludens-2, and toll-like receptor-4 in the small intestine, and interleukin-1β in the hippocampi of mice. Our findings provide solid evidence to support the development of K. pastoris KM71H as a new probiotic with antidepressant-like effects.

Ellagic acid through attenuation of neuro-inflammatory response exerted antidepressant-like effects in socially isolated mice

Recent studies have been demonstrated that neuroinflammation plays a crucial role in the pathophysiology of depression. Therefore, anti-inflammatory medications could be regarded as a potentially effective treatments for depression. Ellagic acid (EA) is a natural polyphenol with antioxidant and anti-inflammatory properties. This study aimed to evaluate the antidepressant-like effect of EA in a mouse model of social isolation stress (SIS), considering its potential anti-neuroinflammatory properties. In this study, 48 male mice were divided into six groups (n = 8), including saline-treated control (socially conditioned (SC)) group and SIS (isolation conditioned (IC)) groups treated with saline or EA at doses of 12.5, 25, 50, and 100 mg/kg, respectively. Saline and EA were administrated intraperitoneally for 14 constant days. Immobility time in the forced swimming test (FST) and grooming activity time in the splash test were measured. The gene expression of inflammatory cytokines relevant to neuroinflammation was assessed in the hippocampus by real-time PCR. Results showed that SIS significantly increased immobility time in the FST and reduced grooming activity time in the splash test. In addition, the expression of inflammatory genes, including TNF-α, IL-1β, and TLR4 increased in IC mice's hippocampi. Findings showed that EA decreased immobility time in the FST and increased grooming activity time in the splash test. Moreover, EA attenuated neuroimmune-response in the hippocampus. In conclusion, finding determined that EA, through attenuation of neuroinflammation in the hippocampus, partially at least, exerted an antidepressant-like effect in the mouse model of SIS.

Intranasal administration of interleukin-4 ameliorates depression-like behavior and biochemical alterations in mouse submitted to the chronic unpredictable mild stress: modulation of neuroinflammation and oxidative stress.

Physical and psychological stress modulates the hypothalamic pituitary adrenal (HPA) axis, and the redox and inflammatory systems. Impairments in these systems have been extensively reported in major depression (MD) patients. Therefore, our study aimed to investigate the effects of the intranasal administration of interleukin-4 (IL-4) in mice with depressive-like behavior induced by chronic unpredictable mild stress (CUMS) for 28days. On the 28th day, mice received IL-4 intranasally (1ng/mouse) or vehicle (sterile saline), and after 30min, they were submitted to behavioral tests or euthanasia for blood collection and removal of the adrenal glands, axillary lymph nodes, spleen, thymus, prefrontal cortices (PFC), and hippocampi (HC). A single administration of IL-4 reversed CUMS-induced depression-like behavior in the tail suspension test and splash test, without evoking locomotor changes. IL-4 administration reduced the plasma levels of corticosterone and the increased weight of suprarenal glands in stressed mice. Moreover, IL-4 restored the expression of nuclear factor erythroid 2-related factor 2 (NRF2), nuclear factor kappa B (NF-kB), interleukin 1 beta (IL-1β), IL-4, brain derived neurotrophic factor (BDNF), and indoleamine 2,3-dioxygenase (IDO) in the PFC and HC and modulated oxidative stress markers in these brain structures in stressed mice. Our results showed for the first time the antidepressant-like effect of IL-4 through the modulation of neuroinflammation and oxidative stress. The potential effect of IL-4 administered intranasally arises as an innovative strategy for MD treatment.

Intermittent Exposure to Aflatoxin B1 Did Not Affect Neurobehavioral Parameters and Biochemical Markers of Oxidative Stress

Aflatoxin B1 (AFB1) is the most common toxic mycotoxin that contaminates food. The treatment of its intoxication and the management of contaminations are a constant subject of health agendas worldwide. However, such efforts are not always enough to avoid population intoxication. Our objective was to investigate whether intermittent exposure to AFB1 would cause any impairment in biochemical and behavioral parameters, intending to simulate an irregular consumption. Male Wistar rats received four AFB1 administrations (250 μg/kg) by intragastric route separated by a 96-h interval. Toxicity was evaluated using behavioral tests (open field, object recognition, nest construction, marble burying, and splash test), biochemical markers of oxidative stress (cerebral cortex, hippocampus, liver, and kidneys), and plasma parameters of hepatic and renal functions. The intermittent exposure caused no modification in body weight gain as well as in organ weight. Both control and AFB1 groups presented similar profiles of behavior to all tests performed. Furthermore, AFB1 administrations alter neither antioxidant defenses nor markers of oxidation in all assayed tissues and in the plasma markers of hepatic and renal functions. Therefore, AFB1 intermittent administration did not cause its common damage from exposure to this toxicant, which must be avoided, and additional studies are required.

Repeated co-exposure to aflatoxin B1 and aspartame disrupts the central nervous system homeostasis: Behavioral, biochemical, and molecular insights.

Several studies demonstrated the toxicity of aspartame (ASP) and aflatoxin B1 (AFB1 ) in preclinical models. Although the majority of these reports assessed the toxic effects of each substance separately, their concomitant exposure and hazardous consequences are scarce. Importantly, the deleterious effects at the central nervous system caused by ASP and AFB1 co-exposure are rarely addressed. We evaluated if concomitant exposure to AFB1 and ASP would cause behavioral impairment and alteration in oxidative status of the brain in male rats. Animals received once a day for 14days AFB1 (250µg/kg, intragastric gavage [i.g.]), ASP (75mg/kg, i.g.), or both substances (association). On day 14, they were subjected to behavioral evaluation, and biochemical and molecular parameters of oxidative status were measured in the cerebral cortex and hippocampus. In the open field test, AFB1 and combination treatments modified the motor, exploratory, and grooming behavior. In the splash test, all treatments caused a reduction in grooming time compared to the control group. An increase in thiobarbituric acid-reactive substances content induced by AFB1 and combination treatments was observed. The antioxidant defenses (vitamin C, nonprotein sulfhydryl, and ferric reducing antioxidant power) were impaired in all groups compared to control. Regarding molecular evaluation, mitochondrial superoxide dismutase-2 immunoreactivity decreased after AFB1 or ASP exposition in the hippocampus. Thus, co-exposure to ASP and AFB1 was potentially more toxic because it aggravated behavioral impairments and oxidative status disbalance in comparison to the groups that received only ASP or AFB1 . Therefore, our data suggest that those substances caused a disruption in brain homeostasis.

Quetiapine effect on depressive-like behaviors, oxidative balance, and inflammation in serum of rats submitted to chronic stress.

Major depressive disorder (MDD) etiology is still not completely understood, and many individuals resist the traditional treatments. Chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, inflammatory changes and oxidative balance are associated with MDD pathophysiology. Quetiapine, a second-generation antipsychotic, induces a better therapeutic response in individuals refractory to traditional treatments. The main objectives of this research were as follows: to evaluate the effect of chronic mild stress (CMS) on depressive-like behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant, and anti-inflammatory effects of quetiapine. The animals were submitted to CMS protocols. At the end of the CMS, the animals were submitted to a chronic treatment for 14days with the following drugs: quetiapine (20mg/kg), imipramine (30mg/kg), and escitalopram (10mg/kg). At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. The animals were euthanized after the behavioral tests, and serum samples were collected. Myeloperoxidase (MPO) activity and interleukin-6 (IL-6) levels were analyzed. CMS induced an increase in depressive-like behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is a relevant phenomenon in the etiology of depression and suggesting that quetiapine induces an antidepressant effect because it reduces oxidative and inflammatory mechanisms.

Fast-onset effects of Pseudospondias microcarpa (A. Rich) Engl. (Anacardiaceae) hydroethanolic leaf extract on behavioral alterations induced by chronic mild stress in mice.

Pseudospondias microcarpa (Anacardiaceae) is a plant widely used traditionally for treating various central nervous system disorders. A previous study in our laboratory confirmed that the hydroethanolic leaf extract (PME) of the plant produces an antidepressant-like effect in rodent models of behavioral despair. However, its effect on depressive-like behavior induced by chronic mild stress (CMS) and its time course of action are still unknown. In this context, the long-term effects of PME on cognitive function and depressive- and anxiety-like behavior caused by CMS were assessed. Male ICR mice were exposed to CMS for nine weeks and anhedonia was evaluated by monitoring sucrose intake (SIT) weekly. PME (30, 100, or 300 mg kg-1) or fluoxetine (FLX) (3, 10, or 30 mg kg-1) was administered to the mice during the last six weeks of CMS. Behavioral tests-coat state, splash test, forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM), open field test (OFT), novelty suppressed feeding (NSF), EPM transfer latency, and Morris water maze (MWM)-were performed after the nine-week CMS period. When the mice were exposed to CMS, their SIT and grooming behavior reduced (splash test), their coat status was poor, they became more immobile (FST and TST), more anxious (OFT, EPM, and NSF), and their cognitive function was compromised (EPM transfer latency and MWM tests). Chronic PME treatment, however, was able to counteract these effects. Additionally, following two (2) weeks of treatment, PME significantly boosted SIT in stressed mice (30 mg kg-1, P<0.05; 100 mg kg-1, P<0.05; and 300 mg kg-1, P<0.001), as compared to four (4) weeks of treatment with FLX. The present findings demonstrate that PME produces a rapid and sustained antidepressant-like action and reverses behavioral changes induced by chronic exposure to mild stressors.

Sex differences in depression-like behaviours in young adult Swiss mice subjected to the sucrose splash test

Background: Although animal models are powerful tools for understanding the mechanism of depression, there are limitations that make it difficult to translate the results obtained in preclinical studies. Methods: Male and female mice (n = 12/group) were submitted to the forced swimming and splash tests. Results: There was no difference between the immobility time of females and male animals in the forced swimming test. In the splash test, females showed lower latency for the first grooming behaviour and lower grooming time when compared to male animals. Conclusions: The findings indicate that male and female Swiss mice may exhibit different behaviours in experi- mental models of depression. However, due to the variation in protocols between laboratories, the results cannot be considered conclusive.

Unleashing lactoferrin's antidepressant potential through the PI3K/Akt/mTOR pathway in chronic restraint stress rats.

Depression is a widespread neuropsychiatric illness whose etiology is yet mysterious. Lactoferrin (LF), an iron-binding glycoprotein, is reported to promote neuroprotection through its role in the modulation of oxidative stress and inflammation. The objective of the present research was to evaluate the efficacy of LF against chronic restraint stress (CRS)-induced depressive behavior in rats. Depression was evidenced by a reduced grooming time in the splash test and an increased immobility time in the tail suspension test (TST) and forced swimming test (FST). This effect was also accompanied by reduced GSH and serotonin levels and elevated lipid peroxidation and corticosterone levels in the hippocampus. Additionally, an exaggerated hippocampal inflammatory response was also shown by a rise in NF-κB (p65) and TNF-α levels and a reduced IL-10 level. Moreover, CRS substantially reduced the BDNF content as well as the protein levels of PI3K, Akt, and mTOR while boosting the GSK3β content. Interestingly, LF therapy significantly improved CRS-induced behavioral and biochemical aberrations, an effect which was suppressed upon pretreatment with LY294002 (PI3K inhibitor). This suggests that the antidepressant potential of LF may be mediated through the modulation of the PI3K/Akt/mTOR signaling pathway. Furthermore, LF succeeded in restoring 5-HT and corticosterone levels, diminishing oxidative stress and ameliorating the inflammatory cascades. Therefore, and for the first time, LF might serve as a promising antidepressant drug through targeting the PI3K/Akt/mTOR pathway.

Emotional-Single Prolonged Stress: A promising model to illustrate the gut-brain interaction

Excessive stress can precipitate depression and anxiety diseases, and damage gastrointestinal functionality and microbiota changes, favoring the development of functional gastrointestinal disorders (FGIDs) – defined by dysregulation in the brain-gut interaction. Therefore, the present study investigated if Emotional-Single Prolonged Stress (E-SPS) induces depressive/anxiety-like phenotype and gut dysfunction in adult Swiss male mice. For this, mice of the E-SPS group were subjected to three stressors sequential exposure: immobilization, swimming, and odor of the predator for 7 days (incubation period). Next, animals performed behavior tests and 24 h later, samples of feces, blood, and colon tissue were collected. E-SPS increased the plasma corticosterone levels, immobility time in the tail suspension and forced swim test, decreased the grooming time in the splash test, OAT%, and OAE% in the elevated plus-maze test, as well as increased anxiety index. Mice of E-SPS had increased % of intestinal transit rate, % of fecal moisture content, and fecal pellets number, and decreased Claudin1 content in the colon. E-SPS decreased the relative abundance of Bacteroidetes phylum, Bacteroidia class, Bacteroidales order, Muribaculaceae and Porphyromonadaceae family, Muribaculum, and Duncaniella genus. However, E-SPS increased Firmicutes and Actinobacteria phylum, Coriobacteriales order, and the ratio of Firmicutes/Bacteroidetes, and demonstrated Mucispirillum genus presence. The present study showed that E-SPS induced depressive/anxiety-like phenotype, predominant diarrhea gut dysfunction, and modulated the gut bacterial microbiota profile in male adult Swiss mice. E-SPS might be a promising model for future studies on the brain-gut interaction and the development of FGIDs with psychological comorbidities.

Behavioral flexibility impacts on coping and emotional responses in male mice submitted to social defeat stress

Behavioral flexibility permits the appropriate behavioral adjustments in response to changing environmental demands. The present study aimed to evaluate if variability in baseline flexibility can enable differences in coping strategies, changes in neuroplasticity, and behavioral outcomes in responses to chronic social defeat stress (CSDS). Male C57BL6 mice were submitted to the Morris Water Maze (MWM) using an extended protocol for reversal learning to assess. The animals were divided into low and high behavioral flexibility groups based on their performance on the last day of acquisition versus the four days of reversal learning. The CSDS was applied for ten consecutive days, and coping strategies were evaluated during the physical interaction on the first and last day of stress. A battery of behavioral tests to assess social and emotional behavior was conducted 24 h after the CSDS protocol. The complexity of prefrontal cortex (PFC) neuronal morphology was evaluated by the Golgi-Cox method. Animals with High Flexibility exhibited changes in their CSDS coping strategies, from active to passive coping, during the CSDS protocol. Low Flexibility mice had no alterations in the coping strategies during CSDS. After social stress, High Flexibility was associated with reduced social interaction with an aggressive Swiss mouse, higher latency to immobility in the tail suspension test, and reduced latency to self-care in the sucrose splash test. High Flexibility mice also displayed higher dendritic complexity on pyramidal neurons from the prelimbic and infralimbic prefrontal cortex compared to Low Flexibility mice. These results suggest That High Flexibility is associated with increased neuroplasticity in cortical areas and better emotional responses related to behavioral despair and motivation. However, exposure to CSDS reversed the beneficial effects of High Flexibility in male mice. Thus, this study suggests that baseline variability in behavioral flexibility, even in inbred strains, might be associated with differences in coping strategies, PFC morphology, and behavioral responses to social stress.

Guanosine Prevents Spatial Memory Impairment and Hippocampal Damage Following Amyloid-β1-42 Administration in Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative illness responsible for cognitive impairment and dementia. Accumulation of amyloid-beta (Aβ) peptides in neurons and synapses causes cell metabolism to unbalance, and the production of reactive oxygen species (ROS), leading to neuronal death and cognitive damage. Guanosine is an endogenous nucleoside recognized as a neuroprotective agent since it prevents glutamate-induced neurotoxicity by a mechanism not yet completely elucidated. In this study, we evaluated behavioral and biochemical effects in the hippocampus caused by the intracerebroventricular (i.c.v.) infusion of Aβ1-42 peptide (400 pmol/site) in mice, and the neuroprotective effect of guanosine (8 mg/kg, i.p.). An initial evaluation on the eighth day after Aβ1-42 infusion showed no changes in the tail suspension test, although ex vivo analyses in hippocampal slices showed increased ROS production. In the second protocol, on the tenth day following Aβ1-42 infusion, no effect was observed in the sucrose splash test, but a reduction in the recognition index in the object location test showed impaired spatial memory. Analysis of hippocampal slices showed no ROS production and mitochondrial membrane potential alteration, but a tendency to increase glutamate release and a significant lactate release, pointing to a metabolic alteration. Those effects were accompanied by decreased cell viability and increased membrane damage. Guanosine treatment prevented behavioral and biochemical alterations evoked by Aβ1-42, suggesting a potential role against behavioral and biochemical damage evoked by Aβ in the hippocampus.

Facile two-step functionalization of multifunctional superhydrophobic cotton fabric for UV-blocking, self cleaning, antibacterial, and oil-water separation

Durable and multifunctional superhydrophobic cotton fabric is highly desired in the modern textile market. However, bottlenecks are the difficult functionalization of desired molecules on hydrophilic cotton fabric and achieving sustainable multifunctional characteristics. Herein, a facile two-step method is proposed to prepare multifunctional superhydrophobic coating on cotton fabric (TiO2-APTES-cotton fabrics). Titanium oxide (TiO2) nanoparticles are anchored at a pristine cotton fabric surface using a fluorine-free aminopropyltriethoxysilane (APTES) coupling agent through an immersion method. The fabric is made hydrophobic by treating it with a 1 % myristic acid (MA) solution via a dip and dry method. Surface morphology, functionalization, surface area, phase, and anti-wetting properties of modified cotton fabric are characterized by SEM, TEM, EDS, FTIR, BET, XRD, XPS, AFM, and optical contact angle measurements. MA-TiO2-APTES-cotton fabric exhibits good mechanical, chemical, and thermal stability, determined by abrasion test, splash test, and washing durability. TiO2 nanoparticles on MA-TiO2-APTES-cotton fabric impart self-cleaning, antifouling, antibacterial, anti-stain, and UV-blocking properties. Myristic acid with long-chain fatty acids reduces the surface energy of cotton fabric, increases the contact angle to 155° ±1, and reduces the tilting angle to 6° ±1. In addition, it is utilized for oil–water separation. The modified superhydrophobic cotton fabric presents good separation efficiency against various oils, such as n-hexane, chloroform, petroleum, toluene, and dichloromethane, with exceptional reusability. This newly designed two-step functionalization approach is simple, cost-effective, green, and shows promise for potential commercial-scale applications.

Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine.

Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e., fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ∼50-63% in patients with pharmaco-resistant depression. Nevertheless, the need to develop reliable treatment response predictors to guide personalized AD strategies and supplement clinical observation is becoming a pressing clinical objective. Here, we propose to establish a proteomic peripheral biomarkers signature of ECT response in an anxio/depressive animal model of non-response to AD. Using an emotionality score based on the analysis complementary behavioral tests of anxiety/depression (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35μg/ml, Cort model) in C57BL/6JRj male mice induced an anxiety/depressive-like behavior. A 28-day chronic fluoxetine treatment (Flx, 18mg/kg/day) reduced corticosterone-induced increase in emotional behavior. A 50% decrease in emotionality score threshold before and after Flx, was used to separate Flx-responding mice (Flx-R, n = 18), or Flx non-responder mice (Flx-NR, n = 7). Then, Flx-NR mice received seven sessions of electroconvulsive seizure (ECS, equivalent to ECT in humans) and blood was collected before and after ECS treatment. Chronic ECS normalized the elevated emotionality observed in Flx-NR mice. Then, proteins were extracted from peripheral blood mononuclear cells (PBMCs) and isolated for proteomic analysis using a high-resolution MS Orbitrap. Data are available via ProteomeXchange with identifier PXD037392. The proteomic analysis revealed a signature of 33 peripheral proteins associated with response to ECS (7 down and 26 upregulated). These proteins were previously associated with mental disorders and involved in regulating pathways which participate to the depressive disorder etiology.

Sex-dependent differences in the stress mitigating and antidepressant effects of selective aryl hydrocarbon receptor modulators

BackgroundOur recent study demonstrated that selective aryl hydrocarbon receptor modulators (SAhRMs), such as 1,4-dihydroxy-2-napthoic acid (DHNA) act as antidepressants in female mice. Given that some effects of certain SAhRMs are known to also be mediated via estrogen receptor signaling, this study examined whether the effects of SAhRMs on mood, emotional state, and cognition are sex-dependent. MethodsC57BL/6N mice were fed with vehicle or 20 mg/kg DHNA for three weeks prior to four weeks of unpredictable chronic mild stress (UCMS). Mice were examined for depression-like behaviors (sucrose preference, forced swim test (FST), splash test, tape groom test), emotional state (open-field test, light/dark test, marble burying, novelty-induced hypophagia, elevated-plus maze), and cognition (object location recognition, novel object recognition, Morris water maze). ResultsIn females, UCMS decreased sucrose preference and increased FST immobility time; both effects were prevented by DHNA. In males, UCMS increased FST immobility time, and increased the latency to groom in the splash test. These effects were not mitigated by DHNA. However, in males, UCMS induced an increase in novelty-induced locomotion, an increase in the time spent in the light compartment in the L/D test, and an increase in the time spent with an object in a novel location. These effects were prevented by DHNA. ConclusionsOur findings indicate that DHNA has high potential to act as antidepressants in females. However, given classical interpretation, DHNA did not appear to act as an antidepressant in males. Nonetheless, our findings indicate that DHNA can mitigate stress effects and reactivity in males.

Involvement of Lateral Habenula Dysfunction in Repetitive Mild Traumatic Brain Injury-Induced Motivational Deficits.

Affective disorders including depression (characterized by reduced motivation, social withdrawal, and anhedonia), anxiety, and irritability are frequently reported as long-term consequences of mild traumatic brain injury (mTBI) in addition to cognitive deficits, suggesting a possible dysregulation within mood/motivational neural circuits. One of the important brain regions that control motivation and mood is the lateral habenula (LHb), whose hyperactivity is associated with depression. Here, we used a repetitive closed-head injury mTBI model that is associated with social deficits in adult male mice and explored the possible long-term alterations in LHb activity and motivated behavior 10-18 days post-injury. We found that mTBI increased the proportion of spontaneous tonically active LHb neurons yet decreased the proportion of LHb neurons displaying bursting activity. Additionally, mTBI diminished spontaneous glutamatergic and GABAergic synaptic activity onto LHb neurons, while synaptic excitation and inhibition (E/I) balance was shifted toward excitation through a greater suppression of GABAergic transmission. Behaviorally, mTBI increased the latency in grooming behavior in the sucrose splash test suggesting reduced self-care motivated behavior following mTBI. To show whether limiting LHb hyperactivity could restore motivational deficits in grooming behavior, we then tested the effects of Gi (hM4Di)-DREADD-mediated inhibition of LHb activity in the sucrose splash test. We found that chemogenetic inhibition of LHb glutamatergic neurons was sufficient to reverse mTBI-induced delays in grooming behavior. Overall, our study provides the first evidence for persistent LHb neuronal dysfunction due to an altered synaptic integration as causal neural correlates of dysregulated motivational states by mTBI.

Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer's Disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Approximately 50% of AD patients show anxiety and depressive symptoms, which may contribute to cognitive decline. We aimed to investigate whether the triple-transgenic mouse (3xTg-AD) is a good preclinical model of this co-morbidity. The characteristic histological hallmarks are known to appear around 6-month; thus, 4- and 8-month-old male mice were compared with age-matched controls. A behavioral test battery was used to examine anxiety- (open field (OF), elevated plus maze, light-dark box, novelty suppressed feeding, and social interaction (SI) tests), and depression-like symptoms (forced swim test, tail suspension test, sucrose preference test, splash test, and learned helplessness) as well as the cognitive decline (Morris water maze (MWM) and social discrimination (SD) tests). Acetylcholinesterase histochemistry visualized cholinergic fibers in the cortex. Dexamethasone-test evaluated the glucocorticoid non-suppression. In the MWM, the 3xTg-AD mice found the platform later than controls in the 8-month-old cohort. The SD abilities of the 3xTg-AD mice were missing at both ages. In OF, both age groups of 3xTg-AD mice moved significantly less than the controls. During SI, 8-month-old 3xTg-AD animals spent less time with friendly social behavior than the controls. In the splash test, 3xTg-AD mice groomed themselves significantly less than controls of both ages. Cortical fiber density was lower in 8-month-old 3xTg-AD mice compared to the control. Dexamethasone non-suppression was detectable in the 4-month-old group. All in all, some anxiety- and depressive-like symptoms were present in 3xTg-AD mice. Although this strain was not generally more anxious or depressed, some aspects of comorbidity might be studied in selected tests, which may help to develop new possible treatments.

Numerical simulations of complex water spray flows around aircraft landing tire

When an aircraft passes through the contaminated runway, the water spray generated by the landing gear may enter the inlet of the engine and affect the operation of the engine. In this paper, the formation of tire spray and the complete splashing trajectory under a complex flow field are calculated by numerical simulations. Firstly, the initial patterns of tire water spray are simulated by the Smoothed Particle Hydrodynamics (SPH)-Finite Element (FE) coupling method in LS-DYNA software package, and the engine flow field is simulated in CFX software package. Secondly, the water spray particles information and engine flow field information are imported into a program to calculate the splashing trajectory under the influence of the complex flow field. In the process, the particles inhaled by the engine are counted, so the engine water inflow can be obtained under different working conditions and tire configurations, which can verify the suppression effect of the tire chine on the engine water inflow. Lastly, the complete splashing trajectory of the complex flow field simulated by the program is consistent with the result of the aircraft splash test, which proves the feasibility of the numerical simulation method for the complete splashing trajectory simulation.