NEFA can serve as good biological markers for the diagnosis of depression in adolescents.

BACKGROUND: The incidence of adolescent depression has markedly risen in recent years, with a high recurrence rate into adulthood. Diagnosis in adolescents is challenging due to subjective factors, highlighting the crucial need for objective diagnostic markers. METHODS: Our study enrolled 204 participants, including healthy controls (n = 88) and first-episode adolescent depression patients (n = 116). Serum samples underwent gas chromatography-mass spectrometry (GC-MS) analysis to assess non-esterified fatty acids (NEFA) expression. Machine learning and ROC analysis were employed to identify potential biomarkers, followed by bioinformatics analysis to explore underlying mechanisms. RESULTS: Nearly all differentially expressed NEFA exhibited significant downregulation. Notably, nonanoic acid, cis-10-pentadecenoic acid, cis-10-carboenoic acid, and cis-11-eicosenoic acid demonstrated excellent performance in distinguishing adolescent depression patients. Metabolite-gene interaction analysis revealed these NEFAs interacted with multiple genes. KEGG pathway analysis on these genes suggested that differentially expressed NEFA may impact PPAR and cAMP signaling pathways. LIMITATIONS: Inclusion of diverse populations for evaluation is warranted. Biomarkers identified in this study require samples that are more in line with the experimental design for external validation, and further basic research is necessary to validate the potential depressive mechanisms of NEFA. CONCLUSIONS: The overall reduction in NEFA expression in first-episode adolescent depression patients suggests a potential mediation of depression symptoms through cAMP and PPAR signaling pathways. NEFA levels show promise as a diagnostic tool for identifying first-episode adolescent depression patients.

IPAC integrates rewarding and environmental memory during the acquisition of morphine CPP.

The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTAGABA) to the IPAC lateral region GABAergic neurons (IPACLGABA) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1-expressing neurons (NAcShD1) to the IPAC medial region GABAergic neurons (IPACMGABA) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTAGABA→IPACLGABA and NAcShD1R→IPACMGABA were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.

Mapping metabolite change in the mouse brain after esketamine injection by ambient mass spectrometry imaging and metabolomics.

Ketamine is a new, fast, and effective antidepression treatment method; however, the possible dissociation effects, sensory changes, abuse risk, and the inability to accurately identify whether patients have a significant response to ketamine limit its clinical use. Further exploration of the antidepressant mechanisms of ketamine will contribute to its safe and practical application. Metabolites, the products of upstream gene expression and protein regulatory networks, play an essential role in various physiological and pathophysiological processes. In traditional metabonomics it is difficult to achieve the spatial localization of metabolites, which limits the further analysis of brain metabonomics by researchers. Here, we used a metabolic network mapping method called ambient air flow-assisted desorption electrospray ionization (AFADESI)-mass spectrometry imaging (MSI). We found the main changes in glycerophospholipid metabolism around the brain and sphingolipid metabolism changed mainly in the globus pallidus, which showed the most significant metabolite change after esketamine injection. The spatial distribution of metabolic changes was evaluated in the whole brain, and the potential mechanism of esketamine's antidepressant effect was explored in this research.

NFATc2-dependent epigenetic downregulation of the TSC2/Beclin-1 pathway is involved in neuropathic pain induced by oxaliplatin.

Neuropathic pain is a common dose-limiting side effect of oxaliplatin, which hampers the effective treatment of tumors. Here, we found that upregulation of transcription factor NFATc2 decreased the expression of Beclin-1, a critical molecule in autophagy, in the spinal dorsal horn, and contributed to neuropathic pain following oxaliplatin treatment. Meanwhile, manipulating autophagy levels by intrathecal injection of rapamycin (RAPA) or 3-methyladenine (3-MA) differentially altered mechanical allodynia in oxaliplatin-treated or naïve rats. Utilizing chromatin immunoprecipitation-sequencing (ChIP-seq) assay combined with bioinformatics analysis, we found that NFATc2 negatively regulated the transcription of tuberous sclerosis complex protein 2 (TSC2), which contributed to the oxaliplatin-induced Beclin-1 downregulation. Further assays revealed that NFATc2 regulated histone H4 acetylation and methylation in the TSC2 promoter site 1 in rats' dorsal horns with oxaliplatin treatment. These results suggested that NFATc2 mediated the epigenetic downregulation of the TSC2/Beclin-1 autophagy pathway and contributed to oxaliplatin-induced mechanical allodynia, which provided a new therapeutic insight for chemotherapy-induced neuropathic pain.

Epigenetic upregulation of hippocampal CXCL12 contributes to context spatial memory-associated morphine conditioning.

Conditioned place preference (CPP) is a learned behavior, in which animals learn to associate environmental contexts with rewarding effects. The formation of CPP is an integrated outcome of multiple learning processes. Although multiple anatomical substrates underlying this contextual learning have been proposed, it remains unknown whether a specific molecular signaling pathway within CA1 mediates context learning associated with morphine conditioning. Here, we showed that repeated context learning associated with morphine conditioning significantly increased CXCL12 levels in hippocampal CA1 neurons, and the inhibition of CXCL12 expression ameliorated the CPP behavior following context exposure with morphine conditioning. Additionally, repeated context exposure with morphine conditioning increased the phosphorylation of STAT3 and the acetylation of histone H4 in CXCL12-expressing neurons in CA1. Immunoprecipitation and chromatin immunoprecipitation assays demonstrated that repeated context exposure with morphine conditioning increased the binding of STAT3 to the CXCL12 gene promoter and the interaction between STAT3 and p300, which contributed to the enhanced transcription of CXCL12 by increasing the acetylation of histone H4 in the CXCL12 gene promoter. The inhibition of STAT3 by intrathecal injection of S3I-201 suppressed the acetylation of histone H4. These data demonstrated the epigenetic upregulation of CXCL12 following repeated context exposure with morphine conditioning, which potentially contributed to the spatial memory consolidation associated with conditioned place preference induced by morphine conditioning.

[Near-infrared luminescence and energy transfer of ACaPO4 : Eu2+, Nd3+ (A = Li, K, Na)].

Near-infrared (NIR) luminescence phosphors ACaPO4 : Eu2+, Nd2+ (A = Li, K, Na) were prepared by conventional solid state method and the sensitization of Nd3+ near-infrared luminescence by Eu2+ was investigated. The characteristic NIR luminescence of Nd3+ in ACaPO4 matrix is greatly enhanced by co-doping of Eu2+. The fluorescence properties of ACaPO4 : Eu2+, the NIR luminescence properties of ACaPO4 : Eu2+, Nd3+ and the fluorescence lifetime were studied. The effect of emission wavelength of Eu2+ on NIR luminescence of Nd3+ was investigated; The energy transfer mechanism between Eu2+ and Nd3+ was also discussed. Emission peak wavelength of Eu2+ In ACaPO4 matrixes was found red shift with the series of A = Li, K, Na and the extent of the overlap with the different excitation peaks of Nd3+ changes obviously. It was concluded that the emission peak position of Eu2+ is a very important factor for energy transfer, and the optimal wavelength range for Eu2+ --> Nd3+ energy transfer is 500 to 550 nm.