Integration of network pharmacology and experimental verification to reveal the active components and molecular mechanism of modified Danzhi Xiaoyao San in the treatment of depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. AIM OF THE STUDY: To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. RESULTS: There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. CONCLUSIONS: These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.

Quantitative proteomics combined independent PRM analysis reveals the mitochondrial and synaptic mechanism underlying norisoboldine's antidepressant effects.

Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidepressant drugs with novel mechanisms. Here, we found that norisoboldine (NOR) showed an antidepressant efficacy in the chronic social defeat stress (CSDS) depression model in the tail suspension, forced swimming, and sucrose consumption tests. We then utilized the drug-treated CSDS mice paradigm to segregate and gain differential protein groups of CSDS versus CON (CSDSCON), imipramine (IMI)-treated versus CSDS (IMICSDS), and NOR-treated versus CSDS (NORCSDS) from the prefrontal cortex. These protein expression alterations were first analyzed by ANOVA with p < 0.05. The protein cluster 1 and cluster 3, in which the pattern of protein levels similar to the mood pattern, showed enrichment in functions and localizations related to mitochondrion, ribosome and synapses. Further GO analysis of the common proteins for NORCSDS groups and NORIMI groups supported the findings from ANOVA analysis. We employed Protein-Protein interaction (PPI) analysis to examine the proteins of NORCSDS and NORIMI, revealing an enrichment of the proteins associated with the mitochondrial ribosomal and synaptic functions. Further independent analysis using parallel reaction monitoring (PRM) revealed that Cox7c, Mrp142, Naa30, Ighm, Apoa4, Ssu72, Mrps30, Apoh, Acbd5, and Cdv3, exhibited regulation in the NOR-treated group to support the homeostasis of mitochondrial functions. Additionally, Dcx, Arid1b, Rnf112, and Fam3c, were also observed to undergo modulation in the NOR-treated groups to support the synaptic formation and functions. These findings suggest that the proteins involved in depression treatment exert effects in strengthen the mitochondrial and synaptic functions in the mice PFC. Western blot analysis supported the data that the levels of Mrpl42, Cox7c, Naa30, Rnf112, Dcx Apoa4, Apoh and Fam3c were altered in the CSDS mice, and rescued by NOR treatment, supporting the PRM data. NOR treatment also rescued the NLRP3 inflammasome activation in CSDS mice. In summary, the current proteomic research conducted on the prefrontal cortex has provided valuable insights into the specific and shared molecular mechanisms underlying pathophysiology and treatment to CSDS-induced depression, shedding light on the therapeutic effects of Norisoboldine.

Moderate embryonic delay of paternal mitochondrial elimination impairs mating and cognition and alters behaviors of adult animals.

Rapid elimination of paternal mitochondria following fertilization is a conserved event in most animals, but its physiological significance remains unclear. We find that modest delay of paternal mitochondrial elimination (PME) in Caenorhabditis elegans embryos unexpectedly impairs mating and cognition of adult animals and alters their locomotion behaviors. Delayed PME causes decreased adenosine triphosphate (ATP) levels in early embryos, which lead to impaired physiological functions of adult animals through an energy-sensing pathway mediated by an adenosine monophosphate (AMP)-activated protein kinase, AAK-2, and a forkhead box class O (FOXO) transcription factor, DAF-16. Treatment of PME-delayed animals with MK-4, a subtype of vitamin K2 that can improve mitochondrial ATP production, restores ATP levels in early embryos, and rescues physiological defects of adult animals. Our results suggest that moderate PME delay during embryo development adversely affects crucial physiological functions in adults, which could be evolutionarily disadvantageous. These observations provide mechanistic explanations for the need to swiftly remove paternal mitochondria early during embryo development.

'Popcorning': an expression of joy, the 'zoomies' or something more sinister?

Following the inaugural Guinea Pig Welfare Forum in September, Josh Loeb discusses the behavioural sensation known as 'popcorning' and what it may mean from a welfare perspective.

Coexistence from a lion's perspective: Movements and habitat selection by African lions (Panthera leo) across a multi-use landscape.

Diminishing wild space and population fragmentation are key drivers of large carnivore declines worldwide. The persistence of large carnivores in fragmented landscapes often depends on the ability of individuals to move between separated subpopulations for genetic exchange and recovery from stochastic events. Where separated by anthropogenic landscapes, subpopulations' connectivity hinges on the area's socio-ecological conditions for coexistence and dispersing individuals' behavioral choices. Using GPS-collars and resource- and step-selection functions, we explored African lion (Panthera leo) habitat selection and movement patterns to better understand lions' behavioral adjustments in a landscape shared with pastoralists. We conducted our study in the Ngorongoro Conservation Area (NCA), Tanzania, a multiuse rangeland, that connects the small, high density lion subpopulation of the Ngorongoro Crater with the extensive Serengeti lion population. Landscape use by pastoralists and their livestock in the NCA varies seasonally, driven by the availability of pasture, water, and disease avoidance. The most important factor for lion habitat selection was the amount of vegetation cover, but its importance varied with the distance to human settlements, season and time of day. Although we noted high levels of individual variation in tolerance for humans, in general lions avoided humans on the landscape and used more cover when closer to humans. Females showed more consistent avoidance of humans and stronger use of cover when near humans than did males. Connectivity of lion subpopulations does not appear to be blocked by sparse pastoralist settlements, and nomadic males, key to subpopulation connectivity, significantly avoided humans during the day, suggesting a behavioral strategy for conflict mitigation. These results are consistent with lions balancing risk from humans with exploitation of livestock by altering their behaviors to reduce potential conflict. Our study lends some optimism for the adaptive capacity of lions to promote coexistence with humans in shared landscapes.

Long-term tracking of social structure in groups of rats.

Rodents serve as an important model for examining both individual and collective behavior. Dominance within rodent social structures can determine access to critical resources, such as food and mating opportunities. Yet, many aspects of the intricate interplay between individual behaviors and the resulting group social hierarchy, especially its evolution over time, remain unexplored. In this study, we utilized an automated tracking system that continuously monitored groups of male rats for over 250 days to enable an in-depth analysis of individual behavior and the overarching group dynamic. We describe the evolution of social structures within a group and additionally investigate how past behaviors influence the emergence of new social hierarchies when group composition and experimental area changes. Notably, we find that conventional individual and pairwise tests exhibit a weak correlation with group behavior, highlighting their limited accuracy in predicting behavioral outcomes in a collective context. These results emphasize the context-dependence of social behavior as an emergent property of interactions within a group and highlight the need to measure and quantify social behavior in more naturalistic environments.

Changes in roosting decisions and group structure following parturition in little brown myotis (Myotis lucifugus).

In many temperate animals, reproductive cycles coincide with seasonal weather changes resulting in behaviour changes such as movement and habitat selection. In social species, these physiological and environmental changes can alter the costs and benefits of social interactions, impacting the structure of animal groups. In little brown myotis (Myotis lucifugus), a gregarious bat occupying much of North America, the pregnancy and lactation phases present different challenges to energy balance and maternal movement, and reduced forage distance has been observed during the lactation period. As such, we hypothesized that differences between reproductive phases alter the roost switching decisions of individual bats and therefore the overall group structure of little brown myotis maternity colonies. We observed that adult females were less likely to switch roosts during the lactation period even when accounting for changing weather conditions. This shift in roost switching behaviour may be the source of observed differences in group structure between reproductive periods. We reported a decline in network cohesiveness, but no meaningful variation in individual roost fidelity and association strengths of dyads between reproductive phases. These results support the contention that reproductive processes in female little brown myotis influence sociality and overall roosting patterns within maternity groups.

Chronic pregabalin treatment reduced anxiety, and acute pregabalin treatment increased depression-like behaviors in rats.

BACKGROUND: Pregabalin is an antiepileptic drug that binds to the alpha-2/delta unit at presynaptic voltage-dependent calcium channels. We aimed to investigate the effect of acute and chronic pregabalin administration on anxiety and depression-like behaviors. METHODS: Fifty-six male Wistar albino rats were divided into seven groups: control, vehicle, and five different dose groups (5, 10, 30, 60, and 100 mg/kg). Pregabalin was administered for two weeks. Depression-like behaviors were evaluated by Forced swimming test. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT), Elevated Plus Maze (EPM), and light-dark box. Subjects underwent the forced swimming test (FST) after the first dose, while the open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB) were performed after two weeks of treatment. Further sucrose preference test was conducted to evaluate anhedonia until the end of the experiment. RESULTS: In the forced swimming test, depression-like behaviors increased after acute single-dose administration of 10, 30, 60, 100 mg/kg pregabalin. According to OFT results, chronic 100 mg/kg pregabalin showed anxiolytic effects by decreasing grooming, and freezing behaviors. In addition, 100 mg/kg chronic pregabalin administration significantly increased the time spent in the central region, the number of entries to the center, and the unsupported rearing number without causing any change in locomotor activity. According to EPM results, both chronic 60 and 100 mg/kg pregabalin treatments showed anxiolytic effects by increasing open arm time and head dipping behavior. In addition, 60 and 100 mg/kg chronic pregabalin administration significantly decreased stretch attend posture. All pregabalin administrations between 5 and 100 mg/kg displayed anxiolytic effects in the LDB. Sucrose preference was above 65% for the duration of all experiments and subjects did not show anhedonia. CONCLUSION: Acute pregabalin treatment triggered depression-like behaviors. Anhedonia, which may be associated with depression, was not observed during chronic treatment. Moreover, chronic treatment with pregabalin revealed potent anxiolytic effects in different behavior patterns and doses for all tests of unconditional anxiety. In particular, 100 mg/kg chronic pregabalin administration decreased anxiety-like behaviors in all experiment setups. Although the anxiolytic effect was demonstrated in chronic treatment, acute treatment of pregabalin induced depression-like behaviors, and thus in clinical practice should be done with caution, especially in patients with anxiety-depression comorbidity.

Towards automatic farrowing monitoring-A Noisy Student approach for improving detection performance of newborn piglets.

Nowadays, video monitoring of farrowing and automatic video evaluation using Deep Learning have become increasingly important in farm animal science research and open up new possibilities for addressing specific research questions like the determination of husbandry relevant indicators. A robust detection performance of newborn piglets is essential for reliably monitoring the farrowing process and to access important information about the welfare status of the sow and piglets. Although object detection algorithms are increasingly being used in various scenarios in the field of livestock farming, their usability for detecting newborn piglets has so far been limited. Challenges such as frequent animal occlusions, high overlapping rates or strong heterogeneous animal postures increase the complexity and place new demands on the detection model. Typically, new data is manually annotated to improve model performance, but the annotation effort is expensive and time-consuming. To address this problem, we propose a Noisy Student approach to automatically generate annotation information and train an improved piglet detection model. By using a teacher-student model relationship we transform the image structure and generate pseudo-labels for the object classes piglet and tail. As a result, we improve the initial detection performance of the teacher model from 0.561, 0.838, 0.672 to 0.901, 0.944, 0.922 for the performance metrics Recall, Precision and F1-score, respectively. The results of this study can be used in two ways. Firstly, the results contribute directly to the improvement of piglet detection in the context of birth monitoring systems and the evaluation of the farrowing progress. Secondly, the approach presented can be transferred to other research questions and species, thereby reducing the problem of cost-intensive annotation processes and increase training efficiency. In addition, we provide a unique dataset for the detection and evaluation of newborn piglets and sow body parts to support researchers in the task of monitoring the farrowing process.

Characteristics of Psychoemotional Manifestations of Laboratory Rodents Undergoing Surgery when Modeling Preoperative Stress.

We studied psychoemotional characteristics and the blood level of corticosterone in sexually mature male C57BL/6 mice (n=40): intact (control), after simulating preoperative stress and surgery, after surgery, and after anesthesia alone. It was found that the anxiety index calculated on the basis of testing in the elevated plus maze was significantly higher in both groups of operated animals. The mice of both operated groups and animals exposed to anesthesia alone showed increased anxiety. Symptoms indicating a high probability of transition of anxiety into a psychoemotional disorder have been recorded.

Excitation-inhibition imbalance in medial preoptic area circuits underlies chronic stress-induced depression-like states.

Dysregulation of brain homeostasis is associated with neuropsychiatric conditions such as major depressive disorder. However, underlying neural-circuit mechanisms remain not well-understood. We show in mice that chronic restraint stress (CRS) and social defeat stress (SDS) are both associated with disruption of excitation (E)-inhibition (I) balance, with increased E/I ratios, in medial preoptic area (MPOA) circuits, but through affecting different neuronal types. CRS results in elevated activity in glutamatergic neurons, and their suppression mitigates CRS-induced depressive-like behaviors. Paraventricular hypothalamic input to these neurons contributes to induction but not expression of depressive-like behaviors. Their projections to ventral tegmental area and periaqueductal gray/dorsal raphe suppress midbrain dopaminergic and serotonergic activity, respectively, and mediate expression of divergent depressive-like symptoms. By contrast, SDS results in reduced activity of GABAergic neurons, and their activation alleviates SDS-induced depressive-like behaviors. Thus, E/I imbalance with relatively increased excitation in MPOA circuits may be a general mechanism underlying depression caused by different etiological factors.

Fiddler crabs (Afruca tangeri) detect second-order motion in both intensity and polarization.

Motion vision is vital for a wide range of animal behaviors. Fiddler crabs, for example, rely heavily on motion to detect the movement of avian predators. They are known to detect first-order motion using both intensity (defined by spatiotemporal correlations in luminance) and polarization information (defined separately as spatiotemporal correlations in the degree and/or angle of polarization). However, little is known about their ability to detect second-order motion, another important form of motion information; defined separately by spatiotemporal correlations in higher-order image properties. In this work we used behavioral experiments to test how fiddler crabs (Afruca tangeri) responded to both second-order intensity and polarization stimuli. Fiddler crabs responded to a number of different intensity based second-order stimuli. Furthermore, the crabs also responded to second-order polarization stimuli, a behaviorally relevant stimulus applicable to an unpolarized flying bird when viewed against a polarized sky. The detection of second-order motion in polarization is, to the best of our knowledge, the first demonstration of this ability in any animal. This discovery therefore opens a new dimension in our understanding of how animals use polarization vision for target detection and the broader importance of second-order motion detection for animal behavior.

Tolerant mothers: aggression does not explain solitary living in the bush Karoo rat.

Many mammal species are thought to adopt solitary living owing to mothers becoming intolerant of adult offspring and the occurrence of social intolerance between adults. However, field studies on how solitary mammals interact are rare. Here we show that solitary living can occur without social intolerance. Over 3 years, we recorded interactions between free-living bush Karoo rats (Otomys unisulcatus) and conducted dyadic encounter experiments between kin and non-kin female neighbours, both in a neutral test arena and in field intruder experiments. Social interactions were rare (230/2062 observations), and they were aggressive in only 34% of cases. In dyadic encounters, mothers interacted amicably with young offspring. Aggression between mothers and offspring was almost absent. This mother-offspring relationship remained amicable even after adult offspring had dispersed. Aggression between neighbouring adult females was low in neutral arena tests, independent of kinship and season. However, in the field, females reacted more aggressively towards non-kin than kin intruders, especially during the breeding season. Tolerance between mothers and adult offspring indicates that aggression is not the mechanism leading to dispersal and solitary living. We found a solitary social system characterized by social tolerance, suggesting that dispersal and lack of social attraction rather than aggression can lead to solitary living.

Genetic parameters of behavior traits of beef cattle classified using wearable devices.

With the development of wearable devices, it is now possible to monitor livestock behavior 24 h a day. In this study, we estimated the genetic parameters of the daily duration of six behaviors (feeding, moving, lying, standing, ruminating while lying, and ruminating while standing) in beef cattle, automatically classified using wearable devices. The devices were attached to 332 Japanese beef cattle at two stations for approximately 5 months. We compared repeatability, Poisson regression, and random regression models using the deviance information criterion. Poisson regression models were selected for all traits at each station, probably because of the non-normal distribution of the phenotypes. The heritability estimates by the Poisson regression models were moderate at each station: 0.67 and 0.68 for feeding, 0.68 and 0.53 for moving, 0.47 and 0.55 for lying, 0.45 and 0.40 for standing, 0.51 and 0.59 for ruminating while lying, and 0.37 and 0.45 for ruminating while standing. The genetic correlations between these traits were all negative at both stations, whereas the residual correlations showed different directions depending on the station. Although validation studies with larger populations are needed to confirm these findings, this study provides fundamental knowledge of the genetic basis of daily behavior in beef cattle.

Partial role of volatile organic compounds in behavioural responses of mice to bedding from cancer-affected congeners.

Tumours induce changes in body odours. We compared volatile organic compounds (VOCs) in soiled bedding of a lung adenocarcinoma male mouse model in which cancer had (CC) versus had not (NC) been induced by doxycycline at three conditions: before (T0), after 2 weeks (T2; early tumour development), after 12 weeks (T12; late tumour development) of the induction. In an earlier study, wild-derived mice behaviourally discriminated between CC and NC soiled bedding at T2 and T12. Here, we sought to identify VOCs present in the same soiled bedding that could have triggered the behavioural discrimination. Solid phase micro-extraction was performed to extract VOCs from 3 g-sample stimuli. While wild-derived mice could discriminate the odour of cancerous mice at a very early stage of tumour development (T2), the present study did not identify VOCs that could explain this behaviour. However, consistent with the earlier behavioural study, four VOCs, including two well-known male mouse sex pheromones, were found to be present in significantly different proportions in soiled bedding of CC as compared to NC at T12. We discuss the potential involvement of non-volatile molecules such as proteins and peptides in behavioural discrimination of early tumour development (T2), and point-out VOCs that could help diagnose cancer.

The Comparative Effects Between Long-Term and Short-Term Treatment of Finasteride on Anxiety-Like and Depression-Like Behaviors in Early Senescent Male Rats.

This study aims to compare the efficacy of 5-alpha-reductase inhibitors (5ARIs) on anxiety and depression between long-term and short-term treatment followed by withdrawal in d-galactose (Dgal)-induced senescent male rats. Thirty-two, 8-week-old, male Wistar rats were divided into two groups: control rats and Dgal-treated rats (150 mg/kg/day; subcutaneously) for 18 weeks. At week 13, Dgal-treated rats were subdivided into three subgroups: (1) vehicle (DgV), (2) long-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 6 weeks (DgF), (3) short-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 2 weeks followed by a 4-week withdrawal period (DgW). Anxiety and depression were assessed using the elevated-plus maze (EPM) and splash test (ST). Blood was collected for biochemical analysis. After euthanasia, the brains were removed to examine brain inflammation, oxidative stress, neuroactive steroids, brain metabolites, and brain senescent markers. We found that DgV rats exhibited metabolic disturbance with a reduced preference index of the EPM, and grooming duration in ST. Increased brain neurotoxic metabolites, along with increased brain inflammation/oxidative stress, and reduced microglia complexity were observed in the DgV rats. Both therapeutic approaches improved metabolic parameters and preference index in the open arm of EPM in Dgal-treated rats, while grooming duration and microglia complexity were increased only in DgF rats. Our results indicate that Fin reduces depression-like and anxiety-like behaviors by reducing brain inflammation, oxidative stress, and brain senescent. In conclusion, long-term treatment with 5ARIs is more effective in alleviating depression than short-term treatment followed by withdrawal in Dgal-induced early senescent male rats.

Basolateral amygdala parvalbumin and cholecystokinin-expressing GABAergic neurons modulate depressive and anxiety-like behaviors.

The basolateral amygdala (BLA) is increasingly recognized as a key regulator of depression and anxiety-like behaviors. However, the specific contribution of individual BLA neurons to these behaviors remains poorly understood. Building on our previous study, which demonstrated increased activity in glutamatergic BLA neurons in response to aversive stimuli and that enhancing inhibition in the BLA can alleviate depressive-like behaviors, we investigated the role of individual BLA GABAergic neurons (BLAGABA) in depressive and anxiety-like phenotypes. To address this question, we employed a comprehensive array of techniques, including c-fos staining, fiber photometry recording, optogenetic and chemogenetic manipulation, and behavior analysis. Our findings indicate that BLAGABA neurons show decreased activity during tail suspension and after chronic social defeat stress (CSDS) during social interaction. High-frequency activation of BLAGABA neurons attenuated depressive and anxiety-like behaviors, while low-frequency activation had no effect. Fiber photometry recordings revealed increased activity in BLA GABAergic neurons expressing somatostatin (SST), parvalbumin (PV), and cholecystokinin (CCK) during footshock aversive stimuli. Moreover, we found increased activity in PV and SST neurons and decreased activity in CCK-GABA neurons in the BLA during tail suspension stress. However, after CSDS, BLAPV neurons displayed decreased activity, while SST and CCK neurons showed no changes during the social interaction test. Behavioral analysis demonstrated that chemogenetic inhibition of PV and CCK-GABA neurons induced depressive and anxiety-like behaviors. whereas SST neuron inhibition had no effect. Conversely, chemogenetic activation of BLAPV neurons alleviated depressive behaviors, and activation of BLACCK-GABA neurons alleviated at least partly both depressive and anxiety-like behaviors. This study provides compelling evidence that BLAPV neurons play a critical role in regulating depressive-like behaviors, and that BLACCK-GABA neurons are involved, at least in part, in modulating both depressive-like and anxiety-like behaviors in mice.

Asperuloside Suppresses the Development of Depression through Wnt3α/GSK-3ß Signal Pathway in Rats.

Depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Traditional Chinese medicine monomer has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. The aim of this study was to investigate the antidepressant-like effects of asperuloside (ASP) and its mechanism. The depression-like behaviors of chronic unpredictable mild stress (CUMS)-exposed rats were evaluated by behavioral tests. At the same time, the behaviors of rats treated with different concentrations of ASP (10, 20, 40 mg/kg) were also evaluated. RNA sequencing was performed to screen for dysregulated genes following ASP treatment. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to state the enriched pathways. Protein expression was detected by Western blotting. With the increase of ASP concentration (over 20 mg/kg), the depression-like behaviors of the rats were alleviated, which was manifested as the increase of the number of entries in the central zone, decrease of immobility time, and the increase of swimming time, sucrose preference, and body weight. ASP activated the Wnt3α/glycogen synthase kinase 3ß (GSK-3ß)/ß-catenin signaling pathway in vivo. Knockdown of ß-catenin reversed the effects of ASP on regulating depression-like behaviors. ASP alleviates depression-like behaviors by activating the Wnt3α/GSK-3ß/ß-catenin signaling pathway, indicating that ASP may be a potential therapeutic drug for treatment of depression.

Strategies for Assessing Autistic-Like Behaviors in Mice.

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).