Efficacy and safety of atropine at different concentrations in prevention of myopia progression in Asian children: a systematic review and Meta-analysis of randomized clinical trials.

AIM: To assess the efficacy versus the adverse effects of various concentrations of atropine in the prevention of myopia in Asian children. METHODS: Databases (PubMed, EMBASE, the Cochrane Library and Web of science) were comprehensively searched from inception to April 2022. Types of studies included were randomized clinical trials (RCTs). The published languages were limited to English. Two researchers assessed the quality of included studies independently using Cochrane risk of bias tool based on the Cochrane Handbook for Systematic Reviews of Interventions. Funnel plots and Egger's test were used for detection of publication bias. Meta-analyses were conducted using STATA (version 15.0; StataCorp). RESULTS: A total of 15 RCTs involving 2268 patients were included in the study. In the atropine group, spherical equivalent progressed at a significantly lower rate [weighted mean difference (WMD)=0.39, 95% confidence interval (CI): 0.23, 0.54] than in the control group. A WMD of 0.15 mm was associated with less axial elongation (95%CI -0.19, -0.10). Different doses showed statistically significant differences (P<0.05) and an improved effect could result from a higher concentration. Changes in photopic pupil size and mesopic pupil size in atropine group is 0.70 mm (95%CI: 0.33, 1.06) and 0.38 mm (95%CI: 0.22, 0.54) more than the control group. In the present Meta-analysis, no changes in accommodative amplitude (AA) were associated with atropine administration. Atropine administration increased the risk of adverse effects by 1.37 times. CONCLUSION: Concentrations of less than 1% atropine are able to effectively retard diopter and axis growth of myopia in Asian children in a dose-dependent manner. Meanwhile, it caused pupil enlargement, but induced no change in the AA within this range. Further study is required to determine the dosage needed to achieve maximum efficacy and minimal side effects.

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion.

AIM: To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy (DR) or retinal vein occlusion (RVO). METHODS: This is a retrospective case control study. The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor (VEGF) for patients diagnosed with macular edema secondary to DR (DME) or RVO (RVO-ME) at Xijing Hospital from August 2021 to July 2022. Meanwhile, aqueous humor samples during vitrectomy from patients with idiopathic macular hole (IMH) were also collected and served as controls. The aqueous humor concentrations of VEGF, platelet-derived factor (PDGF), interleukin (IL)-6, IL-8, IL-18, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) were measured with Human Premixed Multi-Analyte Kit (Luminex). The difference of the aqueous cytokines and the correlation between the two diseases were analyzed. RESULTS: A total of 40 eyes of 38 patients were enrolled in the study, including 13 eyes of 11 DME patients (DME group), 16 eyes of 16 RVO-ME patients (RVO-ME group) and 11 eyes of 11 IMH patients (control group). The VEGF, PDGF, IL-6, IL-8, and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group (all P<0.05), the levels of TNF-α was higher in the DME group than in the control group (P<0.05). The VEGF, IL-6, MCP-1, and TNF-α levels in the aqueous humor were significantly higher in the DR group than those in the RVO group (all P<0.05). Correlation analyses revealed that there were complex positive correlations between IL-6, IL-8, IL-18, MCP-1, and TNF-α levels in the aqueous humor of eyes with two diseases. CONCLUSION: Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME, the roles of these factors are more significant or more likely to be activated in DR patients, suggesting different treatment strategies should be considered for the two diseases.

CircSYNDIG1 ameliorates stress-induced abnormal behaviors by suppressing miR-344-5p in mice.

Circular RNA (circRNA) plays an important role in diverse stress-related neuropsychiatric disorders like depression, anxiety and cognitive disorders. Here, using a circRNA microarray, we found that circSYNDIG1, an unreported circRNA, was significantly downregulated in the hippocampus of chronic unpredictable mild stress (CUMS) mice and further validated this finding in corticosterone (CORT) and lipopolysaccharide (LPS) mice by qRT-PCR, and it was negatively correlated with depressive- and anxiety-like behaviors of these three stressed mice. Furthermore, the interaction of miR-344-5p and circSYNDIG1 was confirmed by in situ hybridization (FISH) assay in hippocampus and dual luciferase reporter assay in 293 T cells. And miR-344-5p mimics could simulate the dendritic spine density reduction, depressive- and anxiety-like behaviors and memory impairment induced by CUMS. Overexpression of circSYNDIG1 in hippocampus significantly ameliorated these abnormal changes induced by CUMS or miR-344-5p. It indicated that circSYNDIG1 functions as an miR-344-5p sponge to inhibit miR-344-5p impact, resulting in the increase of dendritic spine density and the subsequent amelioration of the abnormal behaviors. Therefore, the downregulation of circSYNDIG1 in hippocampus participates in CUMS-induced depressive and anxiety-like behavior of mice though miR-344-5p. These findings represent the first evidence for the involvement of circSYNDIG1 and its coupling mechanism in depression and anxiety, suggesting that circSYNDIG1 and miR-344-5p might be new targets for the treatment of stress-related disorder.

Hippocampal semaphorin 3B improves depression-like behaviours in mice by upregulating synaptic plasticity and inhibiting neuronal apoptosis.

Depression is a global health problem, and there is a pressing need for a better understanding of its pathogenesis. Semaphorin 3B (Sema 3B) is an important axon guidance molecule that is primarily expressed in neurons and contributes to synaptic plasticity. Our previous studies using a high-throughput microarray assay suggested that Sema 3B expression was tremendously decreased during the development of depression, but the specific role and mechanisms of Sema 3B in depression are still unknown. Herein, we report that levels of Sema 3B protein are decreased in the hippocampus and serum of chronic mild stress (CMS)-treated mice. Increasing the levels of Sema 3B, either by injecting AAV-Sema 3B into the hippocampus or by injecting recombinant Sema 3B protein into the lateral ventricles, alleviated CMS-induced depression-like behaviours and enhanced the resistance to acute stress by increasing dendritic spine density in hippocampal neurons. In contrast, interfering with the function of Sema 3B by injecting anti-Sema 3B antibody into the lateral ventricles decreased the resistance to acute stress. In vitro, corticosterone (CORT) treatment decreased the survival rate and protein levels of Sema 3B and synapse-associated proteins in HT22 cells. Overexpression of Sema 3B improved the decreased survival rate caused by CORT by inhibiting apoptosis and increasing levels of synaptic-associated proteins, and knockdown of Sema 3B reduces the cellular resistance to CORT and the levels of synapse-associated proteins. These findings represent the first evidence for the neuroprotective mechanism of Sema 3B against stresses, suggesting that Sema 3B could be a promising novel target for the prevention and treatment of depression.

Maternal exposure to triclosan during lactation alters social behaviors and the hippocampal ultrastructure in adult mouse offspring.

We recently reported that exposure to triclosan (TCS), a broad-spectrum antibacterial agent, affects social behaviors in adult mice, however, the long-lasting effects of TCS exposure during early life on social behaviors are still elusive. The present study aimed to investigate the long-lasting impacts of adding TCS to the maternal drinking water during lactation on the social behaviors of adult mouse offspring and to explore the potential mechanism underlying these effects. The behavioral results showed that TCS exposure decreased body weight, increased depression-like behavior and decreased social dominance in both male and female offspring, as well as increased anxiety-like behavior and bedding preference in female offspring. In addition, enzyme-linked immunosorbent assay (ELISA) indicated that TCS exposure increased peripheral proinflammatory cytokine levels, altered serum oxytocin (OT) levels, and downregulated the expression of postsynaptic density protein 95 (PSD-95) in the hippocampus. Morphological analysis by transmission electron microscopy (TEM) demonstrated that exposure to TCS induced morphological changes to synapses and neurons in the hippocampus of offspring. These findings suggested that TCS exposure during lactation contributed to abnormal social behaviors accompanied by increased peripheral inflammation and altered hippocampal neuroplasticity, which provides a deeper understanding of the effects of TCS exposure during early life on brain function and behavioral phenotypes.

Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors.

Major depressive disorder (MDD) is one of the most debilitating and severe mental diseases globally. Increasing evidence has shown that epigenetics is critical for understanding brain function and brain disorders, including MDD. N-acetyltransferase 10 (NAT10), acting on histones, mRNA and other substrates, has been reported to be involved in epigenetic events, including histone acetylation and mRNA modifications. NAT10 is highly expressed in the brain. However, the potential effects of NAT10 on MDD are still unknown. Here, we exploited chronic mild stress (CMS) to induce anxiety- and depression-like behaviors in mice and found that the expression of NAT10 in the mouse hippocampus was upregulated after CMS treatment. Inhibition of NAT10 by pharmacological methods produced anxiolytic- and antidepressant-like effects. Neuron-specific overexpression of NAT10 in the hippocampus resulted in anxiety- and depression-like behaviors, accompanied by higher SIRT1 protein levels, and lower dendritic spine densities. Overall, it was found that elevation of NAT10 in hippocampal neurons is involved in the occurrence of anxiety- and depression-like behaviors, suggesting that NAT10 could be a potential new target for developing anxiolytics and antidepressants.

Enhanced bioelectrochemical performance of microbial fuel cell with titanium dioxide-attached dual metal organic frameworks grown on zinc aluminum - layered double hydroxide as cathode catalyst.

In this study, a three-step distributed feeding method was used to prepare TiO2-attached dual CoZn-metal organic frameworks growing on ZnAl-layered double hydroxide (TiO2@ZIF-67/ZIF-8@ZnAl-LDH) as cathode catalyst of microbial fuel cell (MFC). The composite material was a composite core-shell structure constructed by multi-layer coating with sheet-like ZnAl-LDH as the base, dual MOFs as the magnetic core and TiO2 as the rough surface. The composite material had crystal planes (009), (110), (101) interface. The rough surface, core-shell core and polyhedral structure of TiO2@ZIF-67/ZIF-8@ZnAl-LDH were observed. The complete distribution of Ti, Zn, Al, and Co in the material was observed and offered active sites. The contents of Ti (15.97 %), Al (5.53 %), Na (5.04 %), N (3.52%), Zn (1.47 %) were found out. TiO2@ZIF-67/ZIF-8@ZnAl-LDH was excellent in electrochemical activity and the maximum power density was 409.6 mW/m2, the stable continuous output voltage was 538.4 mV for 8 d.

Sulfur dioxide derivatives attenuates consolidation of contextual fear memory in mice.

Post-traumatic stress disorder (PTSD) is characterized by an enhancement of traumatic memory. Intervention strategies based on the different stages of memory have been shown to be effective in the prevention and control of PTSD. The endogenous gaseous molecule, sulfur dioxide (SO2), has been reported to significantly exert neuromodulatory effects; however, its regulation of learning and memory remains unestablished. This study aimed to investigate the effects of exogenous SO2 derivatives administration on the formation, consolidation, reconsolidation, retention, and expression of contextual fear memory. Behavioral results showed that both intraperitoneal injection (50 mg/kg, ip) and hippocampal infusion (5 µg/side) of SO2 derivatives (a mixture of sodium sulfite and sodium bisulfite, Na2SO3/NaHSO3, 3:1 M/M) significantly impaired consolidation but had no effect on reconsolidation and retention of contextual fear memory. These findings suggest that the attenuating effects of SO2 on the consolidation of fear memory involves, at least partially, the region of the hippocampus. The findings of this study provide direct evidence for the development of new strategies for PTSD prevention and treatment involving the use of gaseous SO2.

Effects of chronic triclosan exposure on social behaviors in adult mice.

Triclosan (TCS), a newly identified environmental endocrine disruptor (EED) in household products, has been reported to have toxic effects on animals and humans. The effects of TCS exposure on individual social behaviors and the potential underlying mechanisms are still unknown. This study investigated the behavioral effects of 42-day exposure to TCS (0, 50, 100 mg/kg) in drinking water using the open field test (OFT), social dominance test (SDT), social interaction test (SIT), and novel object recognition task (NOR). Using 16S rRNA sequencing analysis and transmission electron microscopy (TEM), we observed the effects of TCS exposure on the gut microbiota and ultrastructure of hippocampal neurons and synapses. Behavioral results showed that chronic TCS exposure reduced the social dominance of male and female mice. TCS exposure also reduced social interaction in male mice and impaired memory formation in female mice. Analysis of the gut microbiota showed that TCS exposure increased the relative abundance of the Proteobacteria and Actinobacteria phyla in female mice. Ultrastructural analysis revealed that TCS exposure induced ultrastructural damage to hippocampal neurons and synapses. These findings suggest that TCS exposure may affect social behaviors, which may be caused by altered gut microbiota and impaired plasticity of hippocampal neurons and synapses.

Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects.

Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Utilizing several approaches including adeno-associated virus (AAV)-mediated overexpression of HO-1, systemic CO-releasing molecules (CO-RMs), CO-rich saline or CO gas treatment procedures in combination with hydrogen peroxide (H2O2)-induced PC12 cell injury model, and lipopolysaccharide (LPS)-induced depression mouse model, the present study aimed to investigate the potential antidepressant- and anxiolytic-like effects of endogenous and exogenous CO administration in vivo and in vitro. The results of in vitro experiments showed that both CO-RM-3 and CO-RM-A1 pretreatment blocked H2O2-induced cellular injuries by increasing cell survival and decreasing cell apoptosis and necrosis. Similar to the effects of CO-RM-3 and CO-RM-A1 pretreatment, AAV-mediated HO-1 overexpression in the dorsal hippocampus produced significant antidepressant-like activities in mice under normal conditions. Further investigation showed that the CO gas treatment significantly blocked LPS-induced depressive- and anxiety-like behaviors in mice. Taken together, our results suggest that the activation of HO-1 and/or exogenous CO administration produces protective effects and exerts antidepressant- and anxiolytic-like effects. These data uncover a novel function of the HO-1/CO system that appears to be a promising therapeutic target for the treatment of depression and anxiety.

Repeated 3,3-Dimethyl-1-butanol exposure alters social dominance in adult mice.

The influence of gut microbiota on brain function and brain disorders has been attracted more and more attention. Trimethylamine N-oxide (TMAO), an indirect metabolite of gut microbiota, has been linked to aging, cognitive impairment, and other brain disorders. However, the relationship between TMAO and social behaviors are still poorly understood. Adult male mice were exposed to drinking water containing 3,3- Dimethyl-1-butanol (DMB), an indirect inhibitors of TMAO, for 21 continuous days followed by a series of behavioral tests to detect the effect of DMB exposure on social behaviors, mainly including social dominance test (SDT), bedding preference test (BP), sexual preference test (SP), social interaction test (SI), open field test (OFT), tail suspension test (TST), forced swim test (FST), novelty suppressed feeding test (NSF), and novel object recognition (NOR) task. In the SDT, compared with the control group, the mice treated with DMB (both 0.2% and 1.0%), both high-ranked and low-ranked mice, showed a reduction in the number of victories. There is no statistical difference on sexual preference, anxiety, depression-like behavior phenotype, and memory formation. In conclusion, the present findings provide direct evidence, for the first time, that repeated DMB exposure produces significant effects on social dominance of adult mice, without any effects on sexual preference, anxiety, depression-like behavior phenotype or memory formation, highlighting the regulatory effects of gut-brain interaction on social behaviors.

Baicalin promotes hippocampal neurogenesis via the Wnt/ß-catenin pathway in a chronic unpredictable mild stress-induced mouse model of depression.

Hippocampal neurogenesis is known to be related to depressive symptoms. Increasing evidence indicates that Wnt/ß-catenin signaling regulates multiple aspects of adult hippocampal neurogenesis. Baicalin is a major flavonoid compound with multiple pharmacological effects such as anti-inflammatory, anti-apoptotic, and neuroprotective effects. The current study aimed to explore the antidepressant effects of baicalin and its possible molecular mechanisms affecting hippocampal neurogenesis via the regulation of the Wnt/ß-catenin signaling pathway. A chronic mild unpredictable stress (CUMS) model of depression was used in the study. The CUMS-induced mice were treated with baicalin (50 and 100 mg/kg) for 21 days, orally, and the fluoxetine was used as positive control drug. The results indicated that baicalin alleviated CUMS-induced depression-like behaviour, and improved the nerve cells' survival of the hippocampal dentate gyrus (DG) in CUMS-induced depression of model mice and increased Ki-67- and doublecortin (DCX)-positive cells to restore CUMS-induced suppression of hippocampal neurogenesis. The related proteins in the Wnt/ß-catenin signaling pathway, which declined in the CUMS-induced depression model of mice, were upregulated after baicalin treatment, including Wingless3a (Wnt3a), dishevelled2 (DVL2), and ß-catenin. Further study found that the phosphorylation rate of glycogen synthase kinase-3ß (GSK3ß) and ß-catenin nuclear translocation increased, as the levels of the ß-catenin target genes cyclinD1, c-myc, NeuroD1, and Ngn2 upregulated after baicalin treatment. In conclusion, these findings suggest that baicalin may promote hippocampal neurogenesis, thereby exerting the antidepressant effect via regulation of the Wnt/ß-catenin signaling pathway.

Sulfur dioxide derivatives produce antidepressant- and anxiolytic-like effects in mice.

Sulfur dioxide (SO2) can be endogenously generated from sulfur-containing amino acids in animals and humans. Increasing evidence shows that endogenous SO2 may act as a gaseous molecule to participate in many physiological and pathological processes. However, the role of SO2 and its derivatives in the central nervous system remains poorly understood. The present study explored the protective effects of exogenous SO2 derivatives (Na2SO3:NaHSO3, 3:1 M/M) on cellular injury in vitro by using the cell proliferation assay (MTS), cell counting kit 8 assay (CCK-8), and cyto-flow assay in the corticosterone (CORT)-induced PC12 cell injury model. We also examined the antidepressant and anxiolytic effects of SO2 derivatives on the chronic mild stress (CMS)-induced depression mouse model by using the open field test, novelty suppressed feeding test, forced swimming test, tail suspension test, and sucrose preference test. In the MTS and CCK-8 assays, we found that preexposure of SO2 derivatives significantly blocked CORT-induced decrease of cellular survival without causing any negative effects. Results from the cyto-flow assay indicated that treatment with SO2 derivatives could reverse CORT-induced early and late apoptosis of PC12 cells. Systemic treatment with SO2 derivatives produced markedly antidepressant- and anxiolytic-like activities in mice under normal condition and rapidly reversed CMS-induced depressive- and anxiety-like behaviors. In conclusion, these findings indicate that exogenous SO2 derivatives show protective properties against the detrimental effects of stress and exert antidepressant- and anxiolytic-like actions. The present study suggests that exogenous SO2 derivatives are potential therapeutic agents for the treatment of depression, anxiety, and other stress-related diseases.

Brazilin Treatment Produces Antidepressant- and Anxiolytic-Like Effects in Mice.

Increasing evidence shows depression relevant to oxidative stress and inflammation. Anti-inflammatory strategies or antioxidants have led to the development of new antidepressants. Brazilin is a natural product from the Chinese traditional medicine Caesalpinia sappan L., exerting anti-inflammatory, antioxidant, anti-platelet concentration, and anti-cancer effects. While the antidepressant effect of brazilin is largely unknown. In present study, we investigated the effects of brazilin on H2O2-induced oxidative injury in PC12 cells and on depression- and anxiety-like behaviors of chronically mild stressed (CMS)-induced depression mice. It was found that brazilin pre-treatment (both 10 and 20 µM) significantly increased cell viability and decreased cell apoptosis in H2O2-treated PC12 cells. Furthermore, repetitive administration of brazilin to CMS-induced depression mice by intraperitoneal injection (10 mg/kg) made the mice significantly lose their latency of feeding in novelty-suppressed feeding test (NSF), have more the sucrose preference in sucrose preference test (SPT), and more time spent in the central zone without affecting their crossing activity in open field test (OFT). These results suggested that brazilin can play a role in antidepressant and anxiolytic-like behaviors for CMS-induced depression mice probably through inhibiting the oxidative stress. Therefore, brazilin is worth to be further explored for treating depressive and anxiety disorders.

Repeated arctigenin treatment produces antidepressant- and anxiolytic-like effects in mice.

Depression is the root of various diseases. It is one of the most debilitating conditions globally. Antidepressant drugs are usually the first-line of depression treatment. Arctigenin (ARC), one of active ingredient of Arctium lappa L, has been found to exert neuroprotective, anti-decrepitude, and anti-inflammatory activities. Thus, the aim of this study was to investigate the potential antidepressant- and anxiolytic-like effects of ARC using acute and chronic mild stress (CMS) mice model. ICR mice model received acute stress or chronic mild stress assessed by open field test (OFT), novelty suppressed feeding (NSF), sucrose preference test (SPT), forced-swimming test (FST), and tail suspension test (TST). After the final test, blood was collected to detect the serum levels of angiogenin (ANG), thrombopoietin (TPO), and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay (ELISA). The behavioral results showed that repeated ARC (10, 30 mg/kg) administration significantly relieved the antidepressant- and anxiolytic-like effects. And repeated ARC administration at the dose of 10 and 30 mg/kg could significantly block depressive- and anxiety-like behaviors caused by CMS. Finally, ELISA results showed that ARC administration increased the serum levels of angiogenin (ANG), thrombopoietin (TPO), and vascular endothelial growth factor (VEGF). Results showed that chronic ARC administration produces antidepressant- and anxiolytic-like effects, which provides direct evidence for the first time that ARC may be a novel strategy for the treatment of depression and even stress-related disorders. The present data supports further exploration for developing ARC administration as a novel therapeutic strategy for depression and even stress-related disorders.

Narirutin produces antidepressant-like effects in a chronic unpredictable mild stress mouse model.

Depression is a highly debilitating and life-threatening mental disorder, which is accompanied by dysregulation of the peripheral and central immune system. Narirutin (NR), which has antioxidant and anti-inflammatory activities, is one of the active constituents isolated from Citrus unshiu. However, its potential antidepressant-like and anxiolytic-like effects are poorly understood. The present study was aimed to investigate whether NR confers an antidepressant-like effect in mice exposed to a chronic mild stress (CMS) model of depression. The results showed that NR treatment for 1 week significantly alleviated the depressive-like behaviours of CMS-exposed mice, as indicated by restored decreased sucrose preference and shortened floating time in the forced swimming test. Moreover, NR treatment significantly blocked the CMS-induced anxiety-like behaviors, including increased time spent in the central zone in the open field test, and shortened the latency to feeding in the novelty suppressed feeding test. Taken together, our findings suggested that NR exerted potential antidepressant-like and anxiolytic-like effects in CMS mice model of depression, which support further exploration into developing NR as a novel agent to treat depression and even other stress-related disorders.

SuHeXiang Essential Oil Inhalation Produces Antidepressant- and Anxiolytic-Like Effects in Adult Mice.

SuHeXiang (SHX) has been used to treat a wide range of diseases, including those related to the central nervous system. However, the effects of SHX on mood disorders are still elusive. This study aimed to investigate the effects of SHX essential oil on stress-induced depression of mice. In an acute stress-induced depression model, mice inhaled vehicle (1% Tween 80) for 10 min or 10% SHX for 10 or 30 min once daily for 12 continuous days. In the chronic mild stress (CMS)-induced depression model, mice were exposed to a 28-d CMS treatment. Tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and novelty suppressed feeding (NSF) test were conducted. In addition, serum levels of angiogenin (ANG), thrombopoietin (TPO), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA) assays. The results showed that in mice exposed to acute stress, repeated SHX inhalation exerted significant antidepressant and anxiolytic activities, and also reduced the serum levels of ANG, TPO, IL-6, and TNF-α. It also significantly reversed the depressive and anxiety-like behaviors, and reduced the serum levels of ANG and TPO in mice exposed to CMS. This is the first report to show that SHX inhalation could produce significant antidepressant and anxiolytic-like effects. These effects might be mediated by SHX ability to modulate the inflammatory response, and reduce dysfunction of vascular genesis and thrombosis. These results support further exploration for developing SHX inhalation as a novel therapeutic strategy for depression and stress-related disorders.