The metabotropic glutamate receptor 2/3 antagonist LY341495 improves working memory in adult mice following juvenile social isolation.

Juvenile social isolation (SI) and neglect have a negative impact on neurodevelopment persistently, which is associated with cognitive dysfunction in neurodevelopmental disorders. Given the critical role of metabotropic glutamate receptors (mGluRs) in synaptic homeostasis of the prefrontal cortex (PFC), pharmacological intervention on mGluRs has been attempted in order to improve cognitive dysfunction in animal models of neurodevelopmental disorder, as well as in clinical trials. Here we examined the effects of the mGluR2/3 antagonist LY341495 on prefrontal synaptic transmission, spatial working memory, and recognition memory in adult C57BL/6J mice that experienced juvenile SI. We found that SI-reared mice exhibited working memory impairment and decreased excitatory presynaptic release probability of pyramidal neurons in the medial PFC compared with group-reared mice. The positive effect of LY341495 on excitatory synaptic transmission in SI-reared mice was more prominent than the effect in group-reared mice. A single treatment with mGluR2/3 antagonist LY341495 significantly improved the performance of SI-reared mice in the Y-maze test but not in the novel object recognition (NOR) test, while repeated treatments were effective in both tasks. These findings suggest that enhancing glutamatergic transmission via inhibition of mGluR2/3 signaling might represent a promising strategy for improving cognitive function in neurodevelopmental disorders.

The expression change of OTUD3-PTEN signaling axis in glioma cells.

BACKGROUND: OTU domain-containing protein 3 (OTUD3), as a deubiquitinase (DUB) belonging to the ovarian tumor protease (OTU) family, has been reported to suppress tumor via OTUD3-PTEN signaling axis. Glioma is the most common primary intracranial tumor with high invasiveness and poor prognosis. Although less than half of the patients have phosphatase and tension homologue deleted in chromosome 10 (PTEN) mutations or homozygous deletions, two-thirds of glioma possess diminished PTEN expression. Hence, it is conceivable that other obscure mechanisms may cause the decreased expression of the PTEN protein. METHODS: OTUD3 expression was assessed in human normal and glioma tissues at The Cancer Genome Atlas (TCGA) database (https://www.cancer.gov/) and Genotype-Tissue Expression (GTEx) database (https://commonfund.nih.gov/GTex). The mRNA levels of OTUD3 in C6 cells and primary astrocytes were detected using real-time fluorescence quantitative PCR. Western blot was performed to assay PTEN and OTUD3 protein expression in C6 cells and primary astrocytes. By generating Kaplan-Meier curves, we predicted the association between OTUD3 expression and prognosis in glioma patients. RESULTS: (I) OTUD3 transcription was markedly downregulated in glioma based on microarray data for gene expression between human gliomas and normal brain samples. (II) The mRNA levels of OTUD3 in C6 cells was significantly lower than that of in primary astrocytes. (III) The expressions of protein PTEN and OTUD3 in C6 cells were significantly decreased when compared with primary astrocytes. (IV) Glioma patients with high expression of OTUD3 had a longer survival time than patients with low expression. CONCLUSIONS: Our present findings demonstrated that low expression of OTUD3 in glioma may be involved in PTEN related glioma and may contribute to patient survival.

Discovery of quality-marker ingredients of Panax quinquefolius driven by high-throughput chinmedomics approach.

BACKGROUND: Quality control of traditional Chinese medicine (TCM) has always been a hot issue to TCM. However, due to the complexity of TCM ingredients, the current quality standards of TCM have problems that are difficult to guarantee clinical efficacy. American ginseng, the dried roots of Pawajc quinquefolium L. (Araliaceae), is a valuable herbal medicine due to various pharmacological effects and huge health benefit, which are associated with numerous active ingredients such as ginsenosides. Although a large number of studies have investigated the active ingredients of American ginseng, Q-markers reflecting comprehensive review on its efficacies has yet been unrevealed. PURPOSE: The study aims to discover the Q-markers of Panax quinquefolius (American ginseng), provides a powerful method to clarify the significant ingredents of TCM and help further discovering extensive quality evaluation model,contributing to a significant improvement of TCM quality standard. METHODS: Mice general status, biochemical indexes assay, urine metabolic profile, and serum metabolic profile were utilized for model replication and efficacy evaluation. The in vitro and in vivo constituents of American ginseng using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS) with Serum Pharmacochemistry of TCM were in-depth investigated. Q-markers that were associated with core markers of therapeutic effects were excavated by a plotting of correlation between marker metabolites and serum constituents (PCMS) approach. RESULTS: Correlation analysis of 41 blood and urine labeled metabolites with 14 serum components showed that 24-methyl-7-cholesten-3ß-ol, zizybeoside II, betulin, ginsenoside Rd, cinnamyl alcohol, pseudoginsenoside F11 is highly correlated with the therapeutic effects of Compound Zaofan Pill (CZP), while pseudoginsenoside F11 and ginsenoside Rd are highly correlated with the therapeutic effects of American ginseng. The six absorbed blood compounds can be considered as potential Q-markers for compound, of which two compounds, such as pseudoginsenoside F11 and ginsenoside Rd, can be considered as potential Q-markers for American ginseng. CONCLUSION: The study has demonstrated that the Chinmedomics is an effective, comprehensive and fire-new method for discovering the Q-markers of TCM, and it may be more reasonable choices to establish quality standards of TCM.

Existence of myodural bridge in the trachemys scripta elegans: indication of its important physiological function / Existencia del puente miodural en trachemys scripta elegans: indicación de su importante función fisiológica

The myodural bridge (MDB) is confirmed that connecting the most of suboccipital muscles to the cervical dura mater through the posterior intervertebral spaces and widely exists in mammals and birds. In order to reveal whether the MDB is universally existing in amniota of vertebrates, we explored the existence and the morphological features of the MDB in the Trachemys scripta elegans. Twenty fresh red-eared slider specimens were observed by the gross anatomy dissection and histological analysis. In the results, three kind of muscles in the postoccipital region of the red-eared slider were found. The rectus capitis dorsum minor muscle originated from the posterior margin of the occiput (C0) and terminated at the spinous process of the atlas (C1). The transversospinales muscle was attached to the vertebral arch and the postzygapophysis of the atlas and extended to the spinous process of the axis (C2). The C2-C3 intertransversales muscle were extended from the postzygapophysis of C2 and the one of C3. The three muscles covered the dorsal interspaces among C0-C3, and meantime they were closely connected with dense connective tissues, which filled in these interspaces. Each of these thick dense connective tissue membranes sent off several short and strong fibrous bundles ventrally to merge with the cervical spinal dura mater. Furthermore the connective tissues connecting these muscles with cervical spinal dura mater directly were revealed under the microscopy and they consisted of parallel and intensive collagen fibers with orientation from dorsal to ventral. In conclusion, this study for the first time demonstrated the existence of the MDB in the testudines, in all of the dorsal atlantooccipital, atlantoaxial and C2-C3 intervertebral spaces. Based on our results and comparative anatomical evidences in recent year, it could be inferred that the MDB might be its highly conserved structure in the evolution of amniota.

Se confirma que el puente miodural (PMD) conecta la mayoría de los músculos suboccipitales con la duramadre cervical a través de los espacios intervertebrales posteriores y existe ampliamente en mamíferos y aves. Para revelar si el MDB existe universalmente en la amniota de vertebrados, exploramos la existencia y las características morfológicas del PMD en Trachemys scripta elegans. Veinte muestras se observaron mediante disección anatómica y análisis histológico. En los resultados, se encontraron tres tipos de músculos en la región occipital. El músculo recto capitis dorsum minor se originó en el margen posterior del occipital (C0) y terminó en el proceso espinoso del atlas (C1). El músculo transverso espinal se unió al arco vertebral y el proceso del atlas y se extendió al proceso espinoso del axis (C2). El músculo intertransversario C2-C3 se extendió entre los procesos transversos de C2 y el de C3. Los tres músculos cubrían los espacios intermedios dorsales entre C0-C3 y, mientras tanto, estaban estrechamente conectados con tejidos conectivos densos, que rellenaban estos espacios. Cada una de estas membranas densas de tejido conectivo envían varios haces fibrosos cortos y fuertes ventralmente para fusionarse con la duramadre espinal cervical. Además, los tejidos conectivos que conectan estos músculos con la duramadre cervical y espinal se revelaron directamente bajo microscopía y consistían en intensas fibras de colágeno, paralelas, con orientación desde dorsal a ventral. En conclusión, este estudio demostró por primera vez la existencia del PMD en los estudios de prueba, en todos los espacios dorsales atlantooccipital, atlantoaxial e intervertebral C2-C3. Sobre la base de nuestros resultados y las evidencias anatómicas comparativas de los últimos años, se podría inferir que el PMD podría ser una estructura altamente conservada en la evolución de la amniota.

Enduring effects of juvenile social isolation on physiological properties of medium spiny neurons in nucleus accumbens.

RATIONALE: Juvenile social isolation (SI) and neglect is associated with a wide range of psychiatric disorders. While dysfunction of the corticolimbic pathway is considered to link various abnormal behaviors in SI models of schizophrenia, the enduring effects of early social deprivation on physiological properties of medium spiny neurons (MSNs) in nucleus accumbens (NAc) are not well understood. OBJECTIVES: This study investigated the impacts of juvenile SI on locomotor activity to methamphetamine (METH) and neurophysiological characteristics of MSNs in the core of NAc. METHODS: Socially isolated C57BL/6 mice experienced single housing for 4 weeks on postnatal day (PND) 21. The locomotor response to METH (1.0 mg/kg) was observed in both socially isolated and group-housed mice at PND 56. The effects of juvenile SI on the excitatory synaptic events in MSNs and the intrinsic excitability of MSNs in NAc core were investigated in other batches during PND 63-70. RESULTS: Socially isolated mice showed locomotor hypersensitivity to METH, although the expression of locomotor sensitization to METH in socially isolated mice was not different from group-housed mice. The recordings from MSNs of SI-reared mice exhibited higher frequency and smaller amplitude of miniature/spontaneous excitatory postsynaptic current than those from group-reared mice. Moreover, SI resulted in increased intrinsic excitability of MSNs in adult mice. CONCLUSIONS: These results demonstrate neuronal hyperactivity in the NAc of socially isolated mice, which could contribute to locomotor hypersensitivity to METH. Furthermore, the findings indicate a biological link between early negative life events and the vulnerability to psychostimulant-induced psychosis in adulthood.

The second terminations of the suboccipital muscles: An assistant pivot for the To Be Named Ligament.

In the last two decades, many studies have focused on the muscles and dense connective tissues located in the suboccipital region. Our study investigated the existence of the second terminations originating from the suboccipital muscles, and the relationship between the variable types of the To Be Named Ligament (TBNL). Anatomical dissection was performed on 35 head-neck specimens. The existence of the second terminations of the suboccipital muscles was confirmed and various types of the TBNL were observed in this study. The second terminations originated from multiple suboccipital muscles including the rectus capitis posterior minor (RCPmi), rectus capitis posterior major (RCPma) and obliquus capitis inferior (OCI) muscles, merged and terminated at the TBNL. The overall incidence of the second terminations of the suboccipital muscles was 34.29% and it varied among the various suboccipital muscle origins. 28.57% of the second terminations originated from the RCPma; 11.43% was from the RCPmi and 8.57% was from the OCI. Furthermore, there was a significant relationship between the existence of second terminations and the particular type of the TBNL. 95% of the arcuate type of the TBNL was accompanied with the second terminations which attached to their turning part, whereas only 10% of all the radiate type of the TBNL was accompanied with the second terminations. This study for the first time described the second terminations originating from multiple suboccipital muscles and demonstrated the relationship with the various types of the TBNL. We speculated that the second terminations maintain the arcuate TBNL and transfer tensile forces to the Myodural Bridge (MDB), thereby modulating the physiological functions of the MDB.

Lead and cadmium-induced oxidative stress impacting mycelial growth of Oudemansiella radicata in liquid medium alleviated by microbial siderophores.

In this study, the effects of siderophores produced by six bacteria on mycelium growth, Cd and Pb accumulation, lipid peroxidation, protein content and antioxidant enzyme in Oudemansiella radicata were investigated in Cd and Pb-containing liquid medium. The results showed that inoculation with siderophore-containing filtrates (SCF) partly enhanced the growth of O. radicata after 15 days, with 0.8-32.4% biomass increase for Cd and 0.7-20.8% for Pb compared to control(s), which lacked siderophore. The maximum enhancement for accumulation were found to be confined to Bacillus sp. FFQ2(s) (26.5%) for Cd and Pseudomonas sp. CY63(s) (158.9%) for Pb. A significant decrease in MDA content indicated that lipid peroxidation in O. radicata was alleviated by siderophores. Besides, antioxidant enzyme SOD and POD activities also displayed obviously decrease in SCF-treated mycelium compared to control(s) treatment, while CAT activity did not present significant change. Protein level in O. radicata treated by SCF increased from 0.3 to 138.0% for Cd and from 10.9 to 107.1% for Pb compared to control(s). Therefore, the present work suggests that microbial siderophores can reduce the toxicity of metals to mycelium and then alleviate heavy metals-inducing oxidative stress in O. radicata.

Synthesis, herbicidal activities, and 3D-QSAR of 2-cyanoacrylates containing aromatic methylamine moieties.

A series of novel 2-cyanoacrylates containing different aromatic rings were synthesized, and their structures were characterized by (1)H NMR, elemental analysis, and single-crystal X-ray diffraction analysis. Their herbicidal activities against four weeds and inhibition of photosynthetic electron transport against isolated chloroplasts (the Hill reaction) were evaluated. Both in vivo and in vitro data showed that the compounds containing benzene, pyridine, and thiazole moieties gave higher activities than those containing pyrimidine, pyridazine, furan, and tetrahedronfuran moieties. To further explore the comprehensive structure-activity relationship on the basis of in vitro data, comparative molecular field analysis (CoMFA) was performed, and the results showed that a bulky and electronegative group around the para-position of the aromatic rings would have the potential for higher activity, which offered important structural insights into designing highly active compounds prior to the next synthesis.