Astragaloside depresses compound action potential in sciatic nerve of frogs involved in L-type Ca2+-channel dependent mechanism.

The sciatic nerve is the largest sensorimotor nerve within the peripheral nervous system (PNS), possessing the ability to produce endogenous neurotrophins. Compound nerve action potentials (CNAPs) are regarded as a physiological/pathological indicator to identify nerve activity in signal transduction of the PNS. Astragaloside (AST), a small-molecule saponin purified from Astragalus membranaceus, is widely used to treat chronic disease. Nonetheless, the regulatory effects of AST on the sciatic nerve remain unknown. Therefore, the present investigation was undertaken to study the effect of AST on CNAPs of frog sciatic nerves. Here, AST depressed the conduction velocity and amplitude of CNAPs. Importantly, the AST-induced responses could be blocked by a Ca2+-free medium, or by applying all Ca2+ channel antagonists (CdCl2/LaCl3) or L-type Ca2+ channel blockers (nifedipine/diltiazem), but not the T-type and P-type Ca2+ channel antagonist (NiCl2). Altogether, these findings suggested that AST may attenuate the CNAPs of frog sciatic nerves in vitro via the L-type Ca2+-channel dependent mechanisms.

Voluntary exercise during puberty promotes spatial memory and hippocampal DG/CA3 synaptic transmission in mice.

Physical exercise has been shown to have an impact on memory and hippocampal function across different age groups. Nevertheless, the influence and mechanisms underlying how voluntary exercise during puberty affects memory are still inadequately comprehended. This research aims to examine the impacts of self-initiated physical activity throughout adolescence on spatial memory. Developing mice were exposed to a 4-wk voluntary wheel running exercise protocol, commencing at the age of 30 d. After engaging in voluntary wheel running exercise during development, there was an enhancement in spatial memory. Moreover, hippocampal dentate gyrus and CA3 neurons rather than CA1 neurons exhibited an increase in the miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents. In addition, there was an increase in the expression of NR2A/NR2B subunits of N-methyl-D-aspartate receptors and α1GABAA subunit of gamma-aminobutyric acid type A receptors, as well as dendritic spine density, specifically within dentate gyrus and CA3 regions rather than CA1 region. The findings suggest that voluntary exercise during development can enhance spatial memory in mice by increasing synapse numbers and improving synaptic transmission in hippocampal dentate gyrus and CA3 regions, but not in CA1 region. This study sheds light on the neural mechanisms underlying how early-life exercise improves cognitive function.

Chromosome-scale assembly and analysis of Melilotus officinalis genome for SSR development and nodulation genes analysis.

Melilotus officinalis is an important legume crop with forage and Chinese medicinal value. The unknown genome of M. officinalis restricted the domestication and utilization of the species and its germplasm resource diversity. A chromosome-scale assembly of the M. officinalis genome was assembled and analysed. The 976.27 Mb of genome was divided into eight chromosomes covering 99.16% of the whole genome. A total of 50022 genes were predicted in the genome. M. officinalis and Melilotus albus shared a common ancestor 0.5-5.65 million years ago (MYA). A genome-wide doubling event occurred 68.93 MYA according to the synonymous nucleotide-substitution values. A total of 552102 tandem repeats were predicted, and 46004 SSR primers of TRs with 10 or more base pairs were developed and designed. The elucidation of the M. officinalis genome provides a compelling model system for studying the genetic, evolutionary and biosynthesis of this legume.

Cordycepin protects islet ß-cells against glucotoxicity and lipotoxicity via modulating related proteins of ROS/JNK signaling pathway.

Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic ß cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM.

Estradiol decreases the excitability of RA projection neurons in adult male zebra finches.

Zebra finches are essential animal models for studying learned vocal signals. The robust nucleus of the arcopallium (RA) plays an important role in regulating singing behavior. Our previous study showed that castration inhibited the electrophysiological activity of RA projection neurons (PNs) in male zebra finches, demonstrating that testosterone modulates the excitability of RA PNs. Testosterone can be converted into estradiol (E2) in the brain through aromatase; however, the physiological functions of E2 in RA are still unknown. This study aimed to investigate the electrophysiological activities of E2 on the RA PNs of male zebra finches through patch-clamp recording. E2 rapidly decreased the rate of evoked and spontaneous action potentials (APs) of RA PNs, hyperpolarized the resting membrane potential, and decreased the membrane input resistance. Moreover, the G-protein-coupled membrane-bound estrogen receptor (GPER) agonist G1 decreased both the evoked and spontaneous APs of RA PNs. Furthermore, the GPER antagonist G15 had no effect on the evoked and spontaneous APs of RA PNs; E2 and G15 together also had no effect on the evoked and spontaneous APs of RA PNs. These findings suggested that E2 rapidly decreased the excitability of RA PNs and its binding to GPER suppressed the excitability of RA PNs. These pieces of evidence helped us fully understand the principle of E2 signal mediation via its receptors to modulate the excitability of RA PNs in songbirds.

Analogies of human speech and bird song: From vocal learning behavior to its neural basis.

Vocal learning is a complex acquired social behavior that has been found only in very few animals. The process of animal vocal learning requires the participation of sensorimotor function. By accepting external auditory input and cooperating with repeated vocal imitation practice, a stable pattern of vocal information output is eventually formed. In parallel evolutionary branches, humans and songbirds share striking similarities in vocal learning behavior. For example, their vocal learning processes involve auditory feedback, complex syntactic structures, and sensitive periods. At the same time, they have evolved the hierarchical structure of special forebrain regions related to vocal motor control and vocal learning, which are organized and closely associated to the auditory cortex. By comparing the location, function, genome, and transcriptome of vocal learning-related brain regions, it was confirmed that songbird singing and human language-related neural control pathways have certain analogy. These common characteristics make songbirds an ideal animal model for studying the neural mechanisms of vocal learning behavior. The neural process of human language learning may be explained through similar neural mechanisms, and it can provide important insights for the treatment of language disorders.

BDNF enhances electrophysiological activity and excitatory synaptic transmission of RA projection neurons in adult male zebra finches.

The singing of songbirds is a complex vocal behavior. It was reported that brain-derived neurotrophic factor (BDNF), a key neurotrophic factor involved in neuronal survival and activity, plays an important role in regulation of songbirds' song behavior. In all song-related nuclei, the electrophysiological activity of robust nucleus of the arcopallium (RA) in the forebrain of songbirds is directly related to birdsong output. Whether BDNF regulates the electrophysiological activity and synaptic transmission of RA causing the change of song behavior need be further explored. In this study, the effects of BDNF on the electrophysiological activity and excitatory synaptic transmission of RA projection neurons (PNs) in adult male zebra finches were investigated using whole-cell patch clamp recordings in vitro. Our results showed that BDNF increased the firing of evoked action potentials in RA PNs and decreased the membrane input resistance and membrane time constant of RA PNs, indicating that BDNF can promote RA PNs excitability by reducing membrane input resistance and membrane time constant. Meanwhile, BDNF increased the frequency rather than amplitude of miniature excitatory postsynaptic currents (mEPSCs) in RA PNs. Moreover, the effects of BDNF on the excitability, intrinsic membrane properties and mEPSCs of RA PNs were blocked by its receptor TrkB antagonist K252a. These results indicate that BDNF via TrkB enhances the excitability and excitatory synaptic transmission of RA PNs in adult male songbirds through presynaptic mechanisms, suggesting a possible cellular mechanism by which BDNF regulates song behavior.

Pectolinarigenin shows lipid-lowering effects by inhibiting fatty acid biosynthesis in vitro and in vivo.

Pectolinarigenin is the main flavonoid compound and presents in Linaria vulgaris and Cirsium chanroenicum. In this study, RNA sequencing (RNA-seq) was applied to dissect the effect of pectolinarigenin on the transcriptome changes in the high lipid Huh-7 cells induced by oleic acid. RNA-seq results revealed that 15 pathways enriched by downregulated genes are associated with cell metabolism including cholesterol metabolism, glycerophospholipid metabolism, steroid biosynthesis, steroid hormone biosynthesis, fatty acid biosynthesis, etc. Moreover, 13 key genes related to lipid metabolism were selected. Among them, PPARG coactivator 1 beta (PPARGC1B) and carnitine palmitoyltransferase 1A (CPT1A) were found to be upregulated, solute carrier family 27 member 1(SLC27A1), acetyl-CoA carboxylase alpha (ACACA), fatty-acid synthase (FASN), 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), etc. were found to be downregulated. Glycolysis/gluconeogenesis, steroid hormone biosynthesis, and fatty acid biosynthesis were all significantly downregulated, according to gene set variation analysis and gene set enrichment analysis. Besides, protein levels of FASN, ACACA, and SLC27A1 were all decreased, whereas PPARγ and CPT1A were increased. Docking models showed that PPARγ may be a target for pectolinarigenin. Furthermore, pectolinarigenin reduced serum TG and hepatic TG, and improved insulin sensitivity in vivo. Our findings suggest that pectolinarigenin may target PPARγ and prevent fatty acid biosynthesis.

Comparison of protective effects of hesperetin and pectolinarigenin on high-fat diet-induced hyperlipidemia and hepatic steatosis in Golden Syrian hamsters.

A comparative study was conducted to determine whether hesperetin and pectolinarigenin could lower total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) in a high-fat diet (HFD)-induced high lipid model in Golden Syrian hamsters. 48 Golden Syrian hamsters (8 weeks old) were fed with a HFD for 15 days. HFD induced significant increases in plasma TC, TG, LDL, and HDL. Then, these high lipid hamsters were divided into four groups and were administered with 0.5% sodium carboxymethyl cellulose (CMC-Na), hesperetin (100 mg/kg/day), pectolinarigenin (100 mg/kg/day) or atorvastatin (1.0 mg/kg/day), for 7 weeks. It was found that pectolinarigenin treatment resulted in significant reductions in body weight, adiposity index, serum levels of TC, TG and hepatic TC, TG and free fatty acid compared to those in control hamsters with hyperlipidemia (P<0.05). However, hesperetin treatment only caused reductions in plasma TC and hepatic TG levels. Besides, the hamsters treated with pectolinarigenin showed a relatively normal hepatic architecture compared to the hepatic steatosis shown in the control group. Moreover, the expressions of fatty-acid synthase (Fasn) and solute carrier family 27 member 1 (Slc27a1) involved in lipid biosynthesis, were suppressed in the pectolinarigenin-treated groups, and the expression of carnitine palmitoyltransferase 1A (Cpt1a) involved in fatty acid oxidation was increased in the pectolinarigenin-treated group. Taken together, these results suggest pectolinarigenin exerts stronger protective effects against hyperlipidemia and hepatic steatosis than hesperetin, which may involve the inhibition of lipid uptake and biosynthesis.

Effect of voluntary wheel running on gut microbiota composition in developing mice.

Introduction: Background: exercise can increase the species and quantity of beneficial gut microbiota, enrich the diversity of microflora, and promote the development of symbiotic bacteria, especially in the stage of ontogeny. However, there is little evidence of the short-term voluntary exercise effect on the gut microbiota in developing mice. Material and method: therefore, we used short-term voluntary wheel running model to study the gut microbiota of developing mice (1 month old), and detected the fecal samples by 16S rRNA gene sequencing. Results: the results showed that after 4 weeks of voluntary wheel running, the body weight of the running group was significantly lower than that of the control group. Conclusion: there was a significant separation between the running group and the control group in beta diversity measures. At the family level, the clostridiales flora of the running group was higher than that of the control group. Compared with the control group, the abundance of parabacteroides flora and anaerovorax flora increased significantly, and the abundance of anaerotruncus flora and odoribacter flora decreased significantly in the running group. These results showed that gut microbiota be affected after short-term voluntary wheel running in developing mice.

Introducción: Introducción: el ejercicio puede aumentar las especies y la cantidad de microbiota intestinal beneficiosa, enriquecer la diversidad de la microflora y promover el desarrollo de bacterias simbióticas, especialmente en la etapa de ontogenia. Sin embargo, hay poca evidencia del efecto del ejercicio voluntario a corto plazo sobre la microbiota intestinal en ratones en desarrollo. Material y método: por lo tanto, utilizamos un modelo de carrera de ruedas voluntario a corto plazo para estudiar la microbiota intestinal de ratones en desarrollo (1 mes de edad) y detectamos las muestras fecales mediante la secuenciación del gen 16S rRNA. Resultados: los resultados mostraron que después de 4 semanas de carrera voluntaria con ruedas, el peso corporal del grupo de carrera fue significativamente más bajo que el del grupo de control. Conclusión: hubo una diferencia significativa entre el grupo de corredores y el grupo de control en las medidas de diversidad beta. A nivel familiar, la flora de clostridiales del grupo de corredores fue mayor que la del grupo de control. En comparación con el grupo de control, la abundancia de flora parabacteroides y flora anaerovorax aumentó significativamente, y la abundancia de flora anaerotruncus y flora odoribacter disminuyó significativamente en el grupo de carrera. Estos resultados mostraron que la microbiota intestinal se ve afectada después de la carrera voluntaria a corto plazo en ratones en desarrollo.

Pectolinarigenin reduces the expression of sterol regulatory element-binding proteins and cellular lipid levels.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that have important roles in the genes involved in lipid biosynthesis. In this study, it was found that the flavonoid pectolinarigenin, reduced the activity of SRE-containing fatty acid synthase (FAS) promoter and the mRNA expressions of SREBP target genes in human hepatoma (Huh-7) cells. Moreover, compared with other flavonoids, pectolinarigenin reduced the mature forms of SREBPs in a dose-dependent manner. The insulin-induced gene (INSIG) and proteasome were not involved in the pectolinarigenin-mediated reduction of mature forms of SREBPs. Pectolinarigenin also reduced the lipid contents in vitro. These results suggest that pectolinarigenin may inhibit lipogenesis through suppressing SREBP activity, at least partially, via the formation of SREBPs mature forms, thereby reducing the expression of their downstream genes related to lipogenesis. To the best of our knowledge, this is the first work that shows how pectolinarigenin affects cellular lipid levels by affecting SREBPs.

Foliar pathogen-induced assemblage of beneficial rhizosphere consortia increases plant defense against Setosphaeria turcica.

Background: Foliar pathogen infection can induce the enrichment of beneficial microbial consortia in plant rhizosphere, but the mechanism for enhanced plant resistance is unclear. Methods: We investigated the effects of foliar pathogen infection on bacterial communities in maize rhizosphere using high throughput sequencing. Results: Maize plants grown in non-sterilized soils displayed stronger defense against the foliar pathogen Setosphaeria turcica than those in sterilized soils. Foliar pathogen infection further triggered the shift in the structure and composition of rhizosphere bacterial communities. The pathogen-infected plants specially promoted rhizosphere colonization of several bacterial taxa. The Pseudomonas genus increased in the rhizosphere after pathogen infection. Other bacterial genera such as Chitinophaga and Flavobacterium were also greatly enriched in the rhizosphere of pathogen-infected plants. Furthermore, the enriched bacterial species were isolated and were shown to interact synergistically to promote biofilm formation. Although both the Chitinophaga and Flavobacterium species did not induce plant defense, the Pseudomonas species markedly increased the resistance of plants against S. turcica. Furthermore, the consortium consisting of the Pseudomonas, Chitinophaga and Flavobacterium species (CONpcf) conferred long-acting disease resistance of maize plants as compared to the individual Pseudomonas species. Furthermore, the inoculation with the CONpcf significantly induced a marked increase in the levels of DIMBOA in maize leaves, indicating that the consortium-induced increases of DIMBOA levels partially contributed to enhancing disease resistance of plants. Conclusions: Foliar infection of maize plants by S. turcica specifically recruited a group of beneficial rhizosphere bacteria, which conferred enhanced plant defense against pathogen infection. This study provided important evidence that above-ground pathogen infection participated in the mediation of below-ground microbiome for regulating plant defense systems.

Transcriptomic and photosynthetic responses to grafting of the Nod1 gene in nodulated and non-nodulated soybeans.

Legume plants form symbiotic relationships with rhizobia to convert N2 into ammonia, and the nodulation status can affect plant development including photosynthesis. However, the relationship between nitrogen fixation and photosynthesis during carbon and nitrogen metabolism remains unclear. This study was undertaken to unravel regulation of nodulation and photosynthesis using a spontaneous nonnodulated soybean mutant by grafting. The results of inheritance and gene mapping showed that the nonnodulated mutant was controlled by a recessive gene overlapped with the reported rj1 locus, and might be a new rj1 allele with 1 bp deletion in the fourth exon in comparison to the sequence of normal nodulation plants. According to grafting results, soybean nodulation is obviously determined by the roots, not the seedlings. Moreover, nitrogen content along with related metabolic enzyme activity, and photosynthetic capacity were enhanced by nonnodulated scions grafted with nodulated roots. Contrary results were obtained for nodulated scions grafted with nonnodulated roots. A total of 853 differentially expressed genes (DEGs) in the leaves and 1874 in the roots were identified by transcriptome analyses of the grafting treatments. We identified 285 differential gene ontology (GO) terms and 57 differential pathway terms identified in the leaves, while 856 differential GO terms and 207 differential pathway terms in the roots. Twenty DEGs interacting at translation level were selected, and the results of transcriptome analyses were verified by q-PCR. These findings indicated that the nodulation-related Nod allelic gene increases the nitrogen content of nonnodulated plants, which affects the enzymes involved in nitrogen metabolism, leading to changes in hormone levels and further regulation of photosynthesis and carbon metabolism.

Acetic Acid-Producing Endophyte Lysinibacillus fusiformis Orchestrates Jasmonic Acid Signaling and Contributes to Repression of Cadmium Uptake in Tomato Plants.

Diverse signaling pathways regulated by phytohormones are essential for the adaptation of plants to adverse environments. Root endophytic bacteria can manipulate hormone-related pathways to benefit their host plants under stress conditions, but the mechanisms underlying endophyte-mediated plant stress adaptation remain poorly discerned. Herein, the acetic acid-producing endophytic bacteria Lysinibacillus fusiformis Cr33 greatly reduced cadmium (Cd) accumulation in tomato plants. L. fusiformis led to a marked increase in jasmonic acid (JA) content and down-regulation of iron (Fe) uptake-related genes in Cd-exposed roots. Accordantly, acetic acid treatment considerably increased the JA content and inhibited root uptake of Cd uptake. In addition, the Cr33-inoculated roots displayed the increased availability of cell wall and rhizospheric Fe. Inoculation with Cr33 notably reduced the production of nitric oxide (NO) and suppressed Fe uptake systems in the Cd-treated roots, thereby contributing to hampering Cd absorption. Similar results were also observed for Cd-treated tomato plants in the presence of exogenous JA or acetic acid. However, chemical inhibition of JA biosynthesis greatly weakened the endophyte-alleviated Cd toxicity in the plants. Collectively, our findings indicated that the endophytic bacteria L. fusiformis effectively prevented Cd uptake in plants via the activation of acetic acid-mediated JA signaling pathways.

Hepatic Knockdown of Endothelin Type A Receptor (ETAR) Ameliorates Hepatic Insulin Resistance and Hyperglycemia Through Suppressing p66Shc-Mediated Mitochondrial Fragmentation in High-Fat Diet-Fed Mice.

BACKGROUND: Emerging evidence from animal studies and clinical trials indicates that systemic inhibition of endothelin1 (ET1) signaling by endothelin receptor antagonists improves pathological features of diabetes and its complications. It is indicated that endothelin type A receptor (ETAR) plays a major role in ET1-mediated pathophysiological actions including diabetic pathology. However, the effects as well as the mechanistic targets of hepatic ET1/ETAR signaling inhibition on the pathology of metabolic diseases remain unclear. This study aimed to investigate the beneficial effects as well as the underlying mechanisms of hepatic ETAR knockdown on metabolism abnormalities in high-fat diet (HFD)-fed mice. METHODS: Mice were fed a HFD to induce insulin resistance and metabolism abnormalities. L02 cells were treated with ET1 to assess the action of ET1/ETAR signaling in vitro. Liver-selective knockdown of ETAR was achieved by tail vein injection of adeno-associated virus 8 (AAV8). Systemic and peripheral metabolism abnormalities were determined in vivo and in vitro. Mitochondrial fragmentation was observed by transmission electron microscope (TEM) and mitoTracker red staining. RESULTS: Here we provided in vivo and in vitro evidence to demonstrate that liver-selective knockdown of ETAR effectively ameliorated hepatic insulin resistance and hyperglycemia in HFD-fed mice. Mechanistically, hepatic ETAR knockdown alleviated mitochondrial fragmentation and dysfunction via inactivating 66-kDa Src homology 2 domain-containing protein (p66Shc) to recover mitochondrial dynamics, which was mediated by inhibiting protein kinase Cδ (PKCδ), in the livers of HFD-fed mice. Ultimately, hepatic ETAR knockdown attenuated mitochondria-derived oxidative stress and related liver injuries in HFD-fed mice. These ETAR knockdown-mediated actions were confirmed in ET1-treated L02 cells. CONCLUSION: This study defined an ameliorative role of hepatic ETAR knockdown in HFD-induced metabolism abnormalities by alleviating p66Shc-mediated mitochondrial fragmentation and consequent oxidative stress-related disorders and indicated that hepatic ETAR knockdown may be a promising therapeutic strategy for metabolic diseases.

miRNA-181a-5p Enhances the Sensitivity of Cells to Cisplatin in Esophageal Adenocarcinoma by Targeting CBLB.

BACKGROUND: Cisplatin (CDDP) is extensively used for esophageal adenocarcinoma (EAC) chemotherapy, while cisplatin resistance is getting worse. microRNA-181a-5p (miR-181a-5p) has been reported to play an important role in various human cancers. However, the effect and underlying mechanism of miR-181a-5p in cisplatin resistance of EAC remain unclear. METHODS: Cisplatin-resistant EAC cells OE19/CDDP and parental sensitive OE19 cells were applied for experiments in vitro. The expressions of miR-181a-5p and CBLB were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. The cisplatin resistance of cells was expressed by cell viability, IC50 and apoptosis rate by using CCK-8 assay or flow cytometry. The interaction between miR-181a-5p and CBLB was evaluated by luciferase reporter assay and RIP assay. In vivo experiments were conducted via the murine xenograft model. RESULTS: miR-181a-5p was highly expressed while CBLB was lowly expressed in OE19 cell lines compared with OE19/CDDP cells. In cisplatin-resistant OE19/CDDP cells, miR-181a-5p up-regulation or CBLB knockdown inhibited cell viability and inducted apoptosis. In cisplatin-sensitive OE19 cells, miR-181a-5p inhibition or CBLB overexpression promoted cell viability and suppressed apoptosis. CBLB was confirmed to be a target of miR-181a-5p, and rescue assay showed CBLB overexpression reversed the suppression of OE19/CDDP cell viability induced by miR-181a-5p up-regulation, and its down-regulation attenuated miR-181a-5p-inhibition-mediated enhancement of OE19 cell viability. In addition, miR-181a-5p up-regulation enhanced the cytotoxicity of cisplatin in EAC in vivo. CONCLUSION: miR-181a-5p enhanced the sensitivity of cells to cisplatin in EAC by targeting CBLB, indicating a promising sensitizer of cisplatin therapy in clinical esophageal cancer.

Dopamine Modulates Excitatory Synaptic Transmission by Activating Presynaptic D1-like Dopamine Receptors in the RA Projection Neurons of Zebra Finches.

Songbirds are useful vertebrate study models for vocal learning and memory. The robust nucleus of the arcopallium (RA) receives synaptic inputs from both the posterior and anterior pathways of the song control system in songbirds. Hence, RA plays an important role in the control of singing. RA receives dopaminergic (DArgic) inputs that increase the excitability of RA projection neurons (PNs). However, the effects of DA on excitatory synaptic transmission are yet to be deciphered. In this study, the effects of DA on the excitatory synaptic transmission of the PNs in the RA of adult male zebra finches were investigated using a whole-cell patch-clamp recording. We observed that DA decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs). The effects of DA were mimicked by the D1-like DA receptor (D1R) agonist, SKF-38393, but not the D2-like DA receptor (D2R) agonist, Quinpirole. Also, the effects of DA were blocked by D1R antagonist, SCH-23390, but not the D2R antagonist, Sulpiride. These results demonstrate that DA modulates excitatory synaptic transmission by acting on D1R in the RA of adult male zebra finches.

[Regulation of androgen on singing behavior and song control system of songbirds].

Androgen plays an important role in singing of songbirds. Recent studies have shown that androgen levels in vivo not only affect the external morphology of songbirds, but also affect their singing behavior. Androgens (including derivatives) affect singing behavior and singing system in many ways. Based mainly on the results from our research group in the zebra finch, this review summarizes the effects of androgen on singing behavior, excitability and synaptic transmission of projection neurons of singing system, and the interaction of androgen with other neurotransmitter receptors in the brain of songbirds.

Cordycepin protects against ß-amyloid and ibotenic acid-induced hippocampal CA1 pyramidal neuronal hyperactivity.

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. ß-Amyloid (Aß) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aß + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aß + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aß + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aß + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A1R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

The Influence of the Degradation of Tetracycline by Free Radicals from Riboflavin-5'-Phosphate Photolysis on Microbial Viability.

Tetracycline (TC) is a broad-spectrum antibiotic compound. Wastewater with TC may have an adverse effect on ecosystems. Riboflavin-5'-phosphate (FMN or flavin mononucleotide) is a non-toxic product of the phosphorylation of vitamin B2 and is required for the proper functioning of the humans. FMN is sensitized to ultraviolet (UV) and blue light radiation, as evidenced by the generation of reactive oxygen species (ROS). This study inspects feasible applications of blue light on FMN so as to develop a valid way of degrading TC by FMN photolysis. We used the increased rate of bacterial survival as a practical indicator of antibiotic degradation. TC in the presence of FMN solution decomposed completely after 20 W/m2 of blue light irradiation (TCF treatment), and the degradation of TC (D-TCF) occurred after the photolytic process. After TCF treatment, colony-forming units (CFUs) of Escherichia coli (E. coli) were determined for the D-TCF solution. The CFU of E. coli preservation was 93.2% of the D-TCF solution (50 µg/mL of TC in the presence of 114 µg/mL of FMN solution treated with 20 W/m2 of blue light irradiation at 25 °C for 1 h) cultivation. The mass spectrum of D-TCF showed diagnostic ion signals at m/z 431.0 and 414.0 Da. The molecular formula of D-TCF was C21H22N2O8, and the exact mass was 430.44 g/mol. TC degradation by FMN photolysis can significantly decrease the antimicrobial ability of TC. The results expressed here regarding the influence of FMN photolysis on TC degradation offer an environmentally sound wastewater treatment method.