RESUMEN
BACKGROUND: Herb-derived therapeutics is an attractive strategy to treat depression. Here we report the ameliorating effects of Sulfuretin, an anti-inflammatory compound in a depressive mouse model. METHODS: Immobility times were obtained in the tail suspension test and forced swim test performed from day 14 to day 16. Quantitative real-time PCR (qRT-PCR) and Western blot were used to measure brain-derived neurotrophic factor (BDNF) and the extracellular signal-regulated kinase (ERK) pathway of the hippocampus tissue on day 17. SL327 was used to block the ERK pathway in mice to evaluate the interaction between Sulfuretin and the ERK pathway. Mice were treated with Sulfuretin for 14 days before lipopolysaccharide (LPS) injection (0.83 mg/kg/day, i.p.) for two days. RESULTS: Behavior tests showed that Sulfuretin dose-dependently decreased immobility times correlated with depression symptoms. BDNF levels and ERK signaling were significantly restored in the Sulfuretin-treated mice, showing the improvement of brain function. Blocking the p-ERK signaling abrogated the effects of Sulfuretin in improving behaviors and levels of BDNF. CONCLUSION: Our study suggests that Sulfuretin exhibits anti-depressive function in LPS-induced depressive mice, in which the ERK signaling plays an essential role.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Lipopolisacáridos , Animales , Conducta Animal , Benzofuranos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Flavonoides , Hipocampo/metabolismo , Lipopolisacáridos/toxicidad , RatonesRESUMEN
BACKGROUND: Glutamatergic system has been known to play a role in the pathogenesis of major depression disorder by inducing N-methyl-d-aspartate receptor-dependent long-term depression (LTD) or metabotropic glutamate receptors (mGluR)-dependent LTD. Here, we characterized the LTD in a chronic social defeat stress (CSDS)-induced depressive mouse model. METHODS: CSDS was used to induce the depressive-like behaviors in C57BL/6 male mice, which were assessed using sucrose preference test and social interaction test. The synaptic strength including LTD and long-term potentiation (LTP) induced by paired-pulse low frequency stimulation (PP-LFS) was measured using whole-cell recording technique. RESULTS: CSDS induced depressive-like behaviors and facilitated PP-LFS-induced LTD in hippocampal CA3-CA1 pathway in the susceptible mice. Interestingly, mGluR5 but not N-methyl-d-aspartate receptor mediated the PP-LFS-induced LTD. In addition, mGluR5 agonist dihydroxyphenylglycine promoted PP-LFS-induced LTD specifically in susceptible mice, which was diminished by activating the BDNF/TrkB signaling pathway. CONCLUSIONS: Our results suggest that mGluR5-dependent LTD might be responsible for the development of depressive-like behaviors in CSDS-induced depression mice model.
Asunto(s)
Antagonistas de Aminoácidos Excitadores , Depresión Sináptica a Largo Plazo , Animales , Potenciales Postsinápticos Excitadores , Humanos , Potenciación a Largo Plazo , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
AIM: Abnormally high levels of homocysteine (Hcy) are associated with autism spectrum disorder. Betaine is a methyl group donor in Hcy metabolism, and is known to prevent noxious Hcy accumulation. This study explored whether betaine could influence Hcy metabolism in a mouse model of autism and ameliorate behavioral abnormalities. METHODS: Pregnant ICR mice were administered valproic acid (VPA) intraperitoneally on Embryonic Day 12.5. Serum Hcy concentrations in the offspring were measured by enzyme-linked immunosorbent assay. Expressions of Hcy-metabolism-related enzymes, betaine-Hcy methyltransferase, cystathionine ß-synthase, and methionine synthase, were measured by quantitative reverse transcription polymerase chain reaction and western blotting. Offspring were treated by either betaine or saline at the age of 8 weeks and serum Hcy concentrations were measured. Social behaviors were assessed by sniff-duration test and three-chamber test. Repetitive behavior was evaluated by marble-burying test. Tail-flick test was performed to measure nociceptive sensitivity. RESULTS: Prenatal VPA-exposed mice showed significantly elevated Hcy concentrations and decreased betaine-Hcy methyltransferase expression. Treatment with betaine could reduce Hcy level in VPA-exposed mice, attenuate social impairment and repetitive behavior, and normalize nociceptive sensitivity in this model. CONCLUSION: Betaine could ameliorate autism-like features and play a beneficial role in a mouse autism model induced by prenatal VPA exposure.
Asunto(s)
Antimaníacos/efectos adversos , Trastorno del Espectro Autista/prevención & control , Betaína/farmacología , Homocisteína/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/prevención & control , Sustancias Protectoras/farmacología , Conducta Social , Ácido Valproico/efectos adversos , Animales , Antimaníacos/administración & dosificación , Trastorno del Espectro Autista/sangre , Trastorno del Espectro Autista/inducido químicamente , Conducta Animal/efectos de los fármacos , Betaína/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Homocisteína/sangre , Ratones , Ratones Endogámicos ICR , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Sustancias Protectoras/administración & dosificación , Ácido Valproico/administración & dosificaciónRESUMEN
Nematode-trapping fungi are a unique and intriguing group of carnivorous microorganisms that can trap and digest nematodes by means of specialized trapping structures. They can develop diverse trapping devices, such as adhesive hyphae, adhesive knobs, adhesive networks, constricting rings, and nonconstricting rings. Nematode-trapping fungi have been found in all regions of the world, from the tropics to Antarctica, from terrestrial to aquatic ecosystems. They play an important ecological role in regulating nematode dynamics in soil. Molecular phylogenetic studies have shown that the majority of nematode-trapping fungi belong to a monophyletic group in the order Orbiliales (Ascomycota). Nematode-trapping fungi serve as an excellent model system for understanding fungal evolution and interaction between fungi and nematodes. With the development of molecular techniques and genome sequencing, their evolutionary origins and divergence, and the mechanisms underlying fungus-nematode interactions have been well studied. In recent decades, an increasing concern about the environmental hazards of using chemical nematicides has led to the application of these biological control agents as a rapidly developing component of crop protection.