Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.

NiCu alloys anchored Co3O4 nanowire arrays as efficient hydrogen evolution electrocatalysts in alkaline and neutral media.

Robust and long-lasting non-precious metal electrocatalysts are essential to achieve sustainable hydrogen production. In this work, we synthesized Co3O4@NiCu by electrodepositing NiCu nanoclusters onto Co3O4 nanowire arrays that were formed in situ on nickel foam. The introduction of NiCu nanoclusters altered the inherent electronic structure of Co3O4, significantly increasing the exposure of active sites and enhancing endogenous electrocatalytic activity. Co3O4@NiCu exhibited overpotentials of only 20 and 73 mV, respectively, at 10 mA cm-2 current densities in alkaline and neutral media. These values were equivalent to those of commercial Pt catalysts. Finally, the electron accumulation effect at the Co3O4@NiCu, along with a negative shift in the d-band center, is finally revealed by theoretical calculations. Hydrogen adsorption on consequent electron-rich Cu sites was effectively weakened, leading to a robust catalytic activity for the hydrogen evolution reaction (HER). Overall, this study proposes a practical strategy for creating efficient HER electrocatalysts in both alkaline and neutral media.

Upregulation of carbonic anhydrase 1 beneficial for depressive disorder.

Carbonic Anhydrase 1 (CAR1) is a zinc-metalloenzyme that catalyzes the hydration of carbon dioxide, and the alteration of CAR1 has been implicated in neuropsychiatric disorders. However, the mechanism underlying the role of CAR1 in major depressive disorder (MDD) remains largely unknown. In this study, we report the decreased level of CAR1 in MDD patients and depression-like model rodents. We found that CAR1 is expressed in hippocampal astrocytes and CAR1 regulates extracellular bicarbonate concentration and pH value in the partial hilus. Ablation of the CAR1 gene increased the activity of granule cells via decreasing their miniature inhibitory postsynaptic currents (mIPSC), and caused depression-like behaviors in CAR1-knockout mice. Astrocytic CAR1 expression rescued the deficits in mIPSCs of granule cells and reduced depression-like behaviors in CAR1 deficient mice. Furthermore, pharmacological activation of CAR1 and overexpression of CAR1 in the ventral hippocampus of mice improved depressive behaviors. These findings uncover a critical role of CAR1 in the MDD pathogenesis and its therapeutic potential.

Pigment epithelium-derived factor may induce antidepressant phenotypes in mice by the prefrontal cortex.

Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein encoded by SERPINF1 and our previous study reported that PEDF may have antidepressant effects. As a key brain region regulating cognition, memory and emotion, the prefrontal cortex (PFC) has been studied extensively in major depressive disorder (MDD), but there are few reports on the relationship between PEDF and the PFC. In this study, enzyme-linked immunosorbent assay showed that the PEDF level was decreased in the plasma of MDD patients compared with that of healthy controls. Western blotting validated that the PEDF expression in the PFC was downregulated in the mouse chronic social defeat stress and rat chronic unpredictable mild stress models of depression. Correspondingly, normal mice overexpressing PEDF in the PFC showed depression-resistant phenotypes. We detected PFC metabolite levels by liquid chromatography-tandem mass spectrometry and found significant upregulation of 5-hydroxyindoleacetic acid, kynurenine, 5-hydroxytryptamine, ornithine and glutamine, and downregulation of 5-hydroxytryptophan, glutamic acid and aspartic acid in PEDF-overexpressing mice compared with control mice, in which no such changes were detected. Combined with the above findings, this provides an insight into a potential mechanism of the antidepressant effects of PEDF via the PFC, which may help to improve understanding of depression pathophysiology.

Exploration of irradiation intensity dependent external in-band quantum yield for ZnO and CuO/ZnO photocatalysts.

Decorating metal oxides with wide band-gap semiconductor nano-particles constitute an important approach for synthesizing nano-photocatalysts, where the photocatalytic activity is attributed to the band diagram related effective charge separation and external in-band quantum yield (EIQY). However, up to now, the correlation between the irradiation intensity and the functionalization of the in-band quantum yield has not yet been explained. In this work, by investigating the photocatalytic activity of ZnO and CuO/ZnO (CZO) nano-photocatalysts under various irradiative intensities, we show that the effective charge separation in the CuO/ZnO band alignment is sensitive to weak illumination, while ZnO exhibits a competitive photocatalytic activity with CZO under strong illumination. As a consequence, by modifying the irradiation intensity, the intrinsic ZnO can achieve a similar photocatalytic activity to that of metal oxide decorated ZnO. Besides, the optimal photocatalytic activity of CZO is found to be reachable by manipulating the pollutant concentration.

Ferritin disorder in the plasma and hippocampus associated with major depressive disorder.

Major depressive disorder (MDD) is a debilitating mental illness that can cause significant emotional disturbances and severe socioeconomic burdens. Rodent and nonhuman primate-based depression models have been studied, such as brain-derived neurotrophic factor (BDNF) and monoamine acid disorder hypotheses, as well as peripheral microbiota disturbances causing MDD; however, the pathogenesis is still largely unknown. This study aims to explore the relationship between ferritin and MDD. First, alterations in ferritin, including ferritin light chain (FTL) and ferritin heavy chain (FTH), in MDD patient plasma compared with healthy control (HC) plasma were detected using ELISA. Then, serum ferritin expression in cLPS-depressed mice was measured by ELISA. The existence of FTH in the hippocampus was validated by immunofluorescence, and the change in FTH levels in the hippocampus of mice injected with cLPS was detected by western blotting. FTL levels in MDD patients were decreased compared with those in HCs. In cLPS-depressed mice, serum ferritin was not different from that in the control group, while the expression of FTH in the hippocampus was significantly reduced in depressed mice. Our findings demonstrate the alteration of ferritin expression in MDD and provide new insight into the pathogenesis of MDD.

Expression, Rapid Purification and Functional Analysis of DnaK from Rhodococcus ruber.

BACKGROUND: Heat shock proteins (HSPs) represent a group of important proteins which are produced by all kinds of organisms especially under stressful conditions. DnaK, an Hsp70 homolog in prokaryotes, has indispensable roles when microbes was confronted with stress conditions. However, few data on DnaK from Rhodococcus sp. were available in the literature. In a previous study, we reported that toluene and phenol stress gave rise to a 29.87-fold and 3.93-fold increase for the expression of DnaK from R. ruber SD3, respectively. Thus, we deduced DnaK was in correlation with the organic solvent tolerance of R. ruber SD3. OBJECTIVE: To elucidate the role of DnaK in the organic solvent tolerance of R. ruber SD3, expression, purification and functional analysis of Dnak from R. ruber SD3 were performed in the present paper. METHODS: In this article, DnaK from R. ruber SD3 was heterologously expressed in E. coli BL21(DE3) and purified by affinity chromatography. Functional analysis of DnaK was performed using determination of kinetics, docking, assay of chaperone activity and microbial growth. RESULTS: The recombinant DnaK was rapidly purified by affinity chromatography with the purification fold of 1.9 and the recovery rate of 57.9%. Km, Vmax and Kcat for Dnak from R. ruber SD3 were 80.8 µM, 58.1 nmol/min and 374.3 S-1, respectively. The recombinant protein formed trimer in vitro, with the calculated molecular weight of 214 kDa. According to in-silico analysis, DnaK interacted with other molecular chaperones and some important proteins in the metabolism. The specific activity of catalase in the presence of recombinant DnaK was 1.85 times or 2.00 times that in the presence of BSA or Tris-HCl buffer after exposure to 54 °C for 1h. E. coli transformant with pET28-dnak showed higher growth than E. coli transformant with pET28 at 43°C and in the presence of phenol, respectively. CONCLUSION: The biochemical properties and the interaction analysis of DnaK from R. ruber SD3 deepened our understanding of DnaK function. DnaK played an important role in microbial growth when R. ruber was subjected to various stress such as heating and organic solvent.

Non-targeted Metabolomics Profiling of Plasma Samples From Patients With Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a neuropsychiatric disorder caused by multiple factors. Although there are clear guidelines for the diagnosis of MDD, the direct and objective diagnostic methods remain inadequate thus far. Methods: This study aims to discover peripheral biomarkers in patients with MDD and promote the diagnosis of MDD. Plasma samples of healthy controls (HCs, n = 52) and patients with MDD (n = 38) were collected, and then, metabolism analysis was performed using ultrahigh-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Heatmap analysis was performed to identify the different metabolites. Meanwhile, receiver operating characteristic (ROC) curves of these differential metabolites were generated. Results: Six differential metabolites were found by LC-MS/MS analysis. Three of these were increased, including L-aspartic acid (Asp), diethanolamine, and alanine. Three were decreased, including O-acetyl-L-carnitine (LAC), cystine, and fumarate. In addition, LAC, Asp, fumarate, and alanine showed large areas under the curve (AUCs) by ROC analysis. Conclusion: The study explored differences in peripheral blood between depressed patients and HCs. These results indicated that differential metabolites with large AUCs may have the potential to be promising biomarkers for the diagnosis of MDD.

Alterations of neurotransmitters and related metabolites in the habenula from CUMS-susceptible and -resilient rats.

Although major depressive disorder (MDD) has caused severe mental harm to overwhelming amounts of patients, the pathogenesis of MDD remains to be studied. Due to the in-depth discussion of the mechanism of new antidepressants like ketamine, the habenula (Hb) was reported to be significant in the onset of MDD and the antidepressant mechanism. In the Hb of depressive-like rodents, various molecular mechanisms and neuronal electrical activities have been reported, but neurotransmitters disorder in response to stress are still unclear. Thus, we divided stress-susceptible and stress-resilient rats after exposure to chronic unpredictable mild stress (CUMS). Multiple metabolites in the Hb were determined by liquid chromatography-tandem mass spectrometry. Based on this approach, we found that glutamate was significantly increased in susceptible group and resilient group, while dopamine was significant decreased in two groups. Gamma-aminobutyric acid was significantly upregulated in susceptible group but downregulated in resilient group. Our study firstly provides quantitative evidence regarding alterations of main neurotransmitters in the Hb of CUMS rats, showing the different role of neurotransmitters in stress susceptibility and stress resilience.

iTRAQ-based proteomics implies inflammasome pathway activation in the prefrontal cortex of CSDS mice may influence resilience and susceptibility.

AIMS: Major depressive disorder, as a destructive mental health disorder, is a major contributor to disability and death. Numerous studies have illustrated that activation of inflammation and fluctuating immune reactions play a crucial role in the physiopathology of depression. The effectiveness of antidepressants is affected by the intensity of the inflammatory response. Thus, we aim to reveal the correlation of inflammatory factors and depression. MAIN METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ™)-based proteomics was applied to verify the quantitation of target proteins in the PFC of chronic social defeat stress (CSDS) model mice. Ingenuity pathway analysis (IPA) was performed to explore related pathways, and the involvement of molecules was validated by western blotting and real time-quantitative polymerase chain reaction (RT-qPCR). KEY FINDINGS: According to the IPA results, CSDS-susceptible mice and CSDS-resilient mice both exhibited alterations of the inflammasome pathway in the PFC. Compared with control mice, susceptible mice subjected to CSDS showed an increased ATP-activated purinergic receptor P2X7 (also known as P2RX7) protein level. Nevertheless, the expression levels of cysteinyl aspartate-specific protease 1 (Caspase 1) and apoptosis-associated speck-like protein containing a CARD (ASC) were reduced in CSDS mice, and downregulation of interleukin-1ß (IL-1ß) was found in susceptible mice. Moreover, no significant difference was found in nuclear factor-κB levels among the three groups. SIGNIFICANCE: CSDS administration leads to dysfunctions of key molecules in the inflammasome pathway, promoting depressive-like behaviors in mice.

Review of surgical robotic systems for keyhole and endoscopic procedures: state of the art and perspectives.

Minimally invasive surgery, including laparoscopic and thoracoscopic procedures, benefits patients in terms of improved postoperative outcomes and short recovery time. The challenges in hand-eye coordination and manipulation dexterity during the aforementioned procedures have inspired an enormous wave of developments on surgical robotic systems to assist keyhole and endoscopic procedures in the past decades. This paper presents a systematic review of the state-of-the-art systems, picturing a detailed landscape of the system configurations, actuation schemes, and control approaches of the existing surgical robotic systems for keyhole and endoscopic procedures. The development challenges and future perspectives are discussed in depth to point out the need for new enabling technologies and inspire future researches.

Major depression accompanied with inflammation and multiple cytokines alterations: Evidences from clinical patients to macaca fascicularis and LPS-induced depressive mice model.

BACKGROUND: Inflammation progress has been consistently implicated in the pathophysiology of major depressive disorder (MDD). However, the underlying mechanism of inflammation and depressive symptoms still far from being fully elucidated. In addition, studies on emotional disorders could also benefit from model of the non-human primates. To explore the difference of serum multi-cytokines levels among the MDD patients and depressed macaca fascicularis as well as LPS-treated mice, thus may find the reliable potential biomarkers for MDD. METHODS: Serum multi-cytokines levels among MDD patients (n = 44) and depressed macaca fascicularis (n = 6) together with controls (n = 22 for human, n = 6 for macaques) were detected by the Bio-Plex cytokines panel. Then five of these serum cytokines in LPS-treated mice were measured via ELISA. Furthermore, these cytokines protein expressions were validated by western blotting in three depression-related regions of LPS-treated mice. RESULTS: Here, we found that MDD patients displayed increased concentration of 13 proinflammatory and anti-inflammatory cytokines accompanied with one decreased cytokine in peripheral serum. Meanwhile, the naturally occurring depression (NOD) macaca fascicularis merely exhibited elevated concentration of 4 peripheral cytokines (IL-6, IL-8, MCP-1, VEGF), which were in accordance with the outcomes of MDD patients. Importantly, the serum and brain tissues of LPS-treated mice also emerged similar cytokines alterations. CONCLUSION: In summary, our findings strengthen the evidence that cytokines were associated with the depression, and the IL-6 and VEGF may as predictive biomarkers for novel diagnostic as well as therapeutic of depression. The hypothalamus may as a key brain region involve in the inflammatory related depressive-like behaviors.

Metabolomic abnormalities of purine and lipids implicated olfactory bulb dysfunction of CUMS depressive rats.

Major depressive disorder (MDD) is a serious mood disorder and leads to a high suicide rate as well as financial burden. The volume and function (the sensitivity and neurogenesis) of the olfactory bulb (OB) were reported to be altered among the MDD patients and rodent models of depression. In addition, the olfactory epithelium was newly reported to decrease its volume and function under chronic unpredictable mild stress (CUMS) treatment. However, the underlying molecular mechanism still remains unclear. Herein, we conducted the non-targeted metabolomics method based on gas chromatography-mass spectrometry (GC-MS) coupled with multivariate statistical analysis to characterize the differential metabolites in OB of CUMS rats. Our results showed that 19 metabolites were categorized into two perturbed pathways: purine metabolism and lipid metabolism, which were regarded as the vital pathways concerned with dysfunction of OB. These findings indicated that the turbulence of metabolic pathways may be partly responsible for the dysfunction of OB in MDD.

Entorhinal cortex-based metabolic profiling of chronic restraint stress mice model of depression.

Despite that millions of people suffer from major depressive disorder (MDD), the mechanism underlying MDD remains elusive. Recently, it has been reported that entorhinal cortex (EC) functions on the regulation of depressive-like phenotype relying on the stimulation of glutamatergic afferent from EC to hippocampus. Based on this, we used liquid chromatography-tandem mass spectrometry method to explore metabolic alterations in the EC of mice after exposed to chronic restraint stress (CRS). Molecular validation was conducted via the application of western blot and RT-qPCR. Through this study, we found significant upregulation of glutamate, ornithine aspartic acid, 5-hydroxytryptophan, L-tyrosine and norepinephrine in CRS group, accompanied with downregulation of homovanillic acid. Focusing on these altered metabolic pathways in EC, we found that gene levels of GAD1, GLUL and SNAT1 were increased. Upregulation of SERT and EAAT2 in protein expression level were also validated, while no significant changes were found in TH, AADC, MAOA, VMAT2, GAD1, GLUL and SNAT1. Our findings firstly provide evidence about the alteration of metabolites and related molecules in the EC of mice model of depression, implying the potential mechanism in MDD pathology.

Different Serotypes of Adeno-Associated Virus Vector- and Lentivirus-Mediated Tropism in Choroid Plexus by Intracerebroventricular Delivery.

Regulation of gene expression by viral vectors is an effective method for researchers to explore the function of gene products in a target tissue. The choroid plexus (CP) is an important target for gene therapy of neuropsychiatric diseases such as Alzheimer's disease and major depressive disorder. However, viral tropism in CP has not been well studied as a result of limited viral vector applications. To identify CP-specific viral vectors, we intracerebroventricularly administered six different serotypes of adeno-associated virus (AAV) vectors (AAV2/1, AAV2/5, AAV2/8, AAV2/9, AAV2-BR1, and AAV2-PHP.eB) and lentivirus in adult mice. Tropism in CP was compared among these viruses. We found that AAV2/5 and AAV2/8 displayed remarkable infections in CP, while AAV2/1 infected both ependymal cells and cells in the CP. Except for the low infection intensity of AAV2/9 and lentivirus in the CP, no infection intensity was found for CP tissues injected with AAV2-BR1 or AAV2-PHP.eB. Green fluorescence protein expression in the CP after AAV2/5 infection was confirmed by Western blotting. AAV2/5-mediated tropism in epithelial cells of the CP was verified by immunostaining with transthyretin. In this study, we identified for the first time that serotype-specific AAVs 5 and 8 may be robust research tools for intracerebroventricular gene delivery.

The 25(OH)D/VDR signaling may play a role in major depression.

Although the current evidences may suggest that the 25(OH)D associated with depression, still there exists conflicting results. In addition, little known is concerning the relationship between the 25(OH)D and the chronic stress-induced depressive-like behaviors. We detected the 25(OH)D levels in serum and the VDR protein expression in different brain regions aiming to explore the relationship between 25(OH)D/VDR signaling and major depression. The chemiluminescent microparticle immunoassay (CMIA) was used to detect the serum concentration of 25(OH)D in patients, the enzyme-linked immunosorbent assay (ELISA) was applied to measure the serum 25(OH)D levels in both CRS-treated and CSDS-treated mice models of MDD. Meanwhile, the VDR protein expression levels were validated among three MDD related brain regions from CRS-treated mice by western blotting. In this study, we mainly observed that the concentration of the 25(OH)D was decreased in the serum of MDD patients comparing to healthy controls. Consistent with the clinical findings, the CRS-treated mice also displayed down-regulated 25(OH)D level comparing with control mice. While in the CSDS model, the serum 25(OH)D status of depressive mice remained unchanged. Moreover, we found the protein level of VDR was significantly decreased in the hippocampus while increased in the hypothalamus of CRS-treated mice. Nevertheless, the prefrontal cortex exhibited no change regarding VDR protein expression compared with control mice. Taken together, these findings further confirmed that the 25(OH)D together with VDR may involve in the pathophysiological mechanism of depression-like behaviors induced by chronic stress.

CombX: Design and experimental characterizations of a haptic device for surgical teleoperation.

BACKGROUND: Haptic devices with active translation and orientation outputs are highly preferred in surgical teleoperation. However, commercial products are expensive, while state-of-the-art research prototypes are difficult to reproduce outside the original laboratories. METHODS: This paper presents the design and experimental characterizations of two styluses for the CombX, a haptic device with both force and torque outputs constructed from two TouchX haptic devices, which have only force outputs at their styluses. The arrangement was optimized to improve the specifications. Additional functions for surgical teleoperation were also integrated. RESULTS: The CombX has a translation workspace larger than 160 × 160 × 160 mm3 . After calibration, it can provide force outputs of up to 16.32 N and torque outputs of up to 316 mNm. The CombX has also been successfully used to teleoperate a continuum surgical manipulator for two surgical tasks. CONCLUSION: The results show that the CombX is a viable option for surgical teleoperation.

A high-throughput LC-MS/MS method for the quantification of four immunosu- ppressants drugs in whole blood.

BACKGROUND: Immunoassays and liquid chromatography tandem mass spectrometry (LC-MS/MS) are two major methods for therapeutic drug monitoring (TDM) of immunosuppressant drugs. Compared to the relatively limited analytical performance and cross reactivities of immunoassays, the LC-MS/MS method is considered as a gold standard; however, the lack of systematic evaluation and standardization needs to be addressed. METHODS: A LC-MS/MS method for the determination of cyclosporine A, sirolimus, tacrolimus, and everolimus was developed. One-step protein precipitation was used to prepare blood samples. The newly developed method was systematically evaluated and validated according to the standard guidelines. RESULTS: The quantitative method for four immunosuppressant drugs in human whole blood was validated according to the guidelines. The lower limits of the measuring interval (LLMI) for cyclosporine A, sirolimus, tacrolimus, and everolimus were 5, 0.5, 0.5, and 0.5 ng/mL, respectively. Linear correlation coefficients were all >0.999. Internal standard-normalized (IS-normalized) matrix correction factor was within the range 0.88-1.17. The average spiked recoveries of five replicates for the four immunosuppressant drugs were in the range 87.4-109.6%. CONCLUSION: An LC-MS/MS method combined with one-step protein precipitation was developed, providing short sample preparation and chromatographic run time, thus allowing easy clinical diagnosis.

Expression, purification and characterization of diguanylate cyclase from Rhodococcus ruber.

Diguanylate cyclases (DGCs) were responsible for the synthesis of second messenger cyclic di-guanosine monophosphate (c-di-GMP), which were involved in various physiological activities of bacterial species. Here, a full-length DGC from Rhodococcus ruber SD3 fused with glutathione-S-transferase (GST) was expressed in E. coli and purified by glutathione agarose resin. The apparent molecular mass of one subunit of the purified diguanylate cyclase with GST tag (GST-DGC) was estimated to be 71.9 kDa by SDS-PAGE, which was approximately in accordance with the theoretical value of 73.0 kDa. The sequence of GST-DGC was confirmed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The blue native PAGE indicated that GST-DGC formed octamer. The optimum pH and temperature for GST-DGC activity were 8.0 and 47 °C, respectively. The fusion protein exhibited high thermostability, and 94% of activity was retained when the protein was incubated at 87 °C for 1 h. Moreover, the fusion protein showed pH stability. The Km, Vmax and Kcat values for GST-DGC enzyme were 9.8 µM, 0.7 µM/min and 1.3 S-1. Some ions such as Zn2+, Mn2+, Fe2+, Ni2+ and Co2+ had inhibitory effects on the activity of the protein, while other ions such as Mg2+, K+ and Na+ slightly activated the protein. The fusion protein also showed rather high stability in the presence of toluene, cyclohexane and n-hexane.

Validation of the targeted metabolomic pathway in the hippocampus and comparative analysis with the prefrontal cortex of social defeat model mice.

The proportion of major depressive disorder (MDD) patients around the world has increased remarkably. Although many studies of MDD have been conducted based on classic hypotheses, like alteration of the hypothalamic-pituitary-adrenal axis or monoamine neurotransmitters, the mechanisms underlying MDD remain unclear. Aiming to further investigate the mechanisms of MDD, liquid chromatography-tandem mass spectrometry was employed to measure target metabolites in the hippocampus (HIPPO) of chronic social defeat stress model mice. Compared with control mice, stress-susceptible mice showed a reduction of 5-hydroxyindoleacetic acid and kynurenic acid in the tryptophan pathway, and an increased level of dopamine in the catecholamine pathway, while stress-resilient mice displayed a reduction of 5-hydroxytryptamine in the tryptophan pathway. The altered levels of key molecules related to the tryptophan or dopamine metabolic pathways were validated by real-time quantitative polymerase chain reaction or western blotting. Comparative analysis with previous targeted metabolomics results in the prefrontal cortex (PFC) of chronic social defeat stress mice revealed that the altered metabolites manifested in specific brain areas, and only the dopamine metabolic pathway was perturbed in both the HIPPO and PFC after stress. Additionally, correlation analysis validated that levels of kynurenic acid in the HIPPO, along with glutamic acid, L-3, 4-dihydroxyphenylalanine, and vanillylmandelic acid in the PFC, were correlated with depression-like behaviors. This study provides a unique perspective on the potential molecular mechanisms of stress susceptibility and stress resilience.