Project description:Clinical studies have demonstrated that exposure to the inhalational general anesthetic nitrous oxide (N2O) produces antidepressant effects in depressed patients. However, the mechanisms underlying the antidepressant effects of N2O remain largely unknown. Neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) synthesis is essential for brain function and underlies the molecular mechanisms of many neuromodulators. We hypothesized that activation of the nNOS/NO pathway in the medial prefrontal cortex (mPFC) might mediate the antidepressant effects of N2O. In this study, we revealed that repeated N2O exposure produced antidepressant-like responses in mice. Our mechanistic exploration showed that repeated N2O exposure increased burst firing activity and that the expression levels of BDNF with nNOS activation were dependent in the mPFC. In particular, the antidepressant-like effects of N2O were also antagonized by local nNOS inhibition in the mPFC. In summary, our results indicated that N2O exposure enhances BDNF expression levels and burst firing rates in an nNOS activation dependent manner, which might underlie the pharmacological mechanism of the antidepressant-like effects of N2O exposure. The present study appears to provide further mechanistic evidence supporting the antidepressant effects of N2O.
Project description:Nitrous oxide (N(2)O) is a major radiative forcing and stratospheric ozone-depleting gas emitted from terrestrial and aquatic ecosystems. It can be transformed to nitrogen gas (N(2)) by bacteria and archaea harboring the N(2)O reductase (N(2)OR), which is the only known N(2)O sink in the biosphere. Despite its crucial role in mitigating N(2)O emissions, knowledge of the N(2)OR in the environment remains limited. Here, we report a comprehensive phylogenetic analysis of the nosZ gene coding the N(2)OR in genomes retrieved from public databases. The resulting phylogeny revealed two distinct clades of nosZ, with one unaccounted for in studies investigating N(2)O-reducing communities. Examination of N(2)OR structural elements not considered in the phylogeny revealed that the two clades differ in their signal peptides, indicating differences in the translocation pathway of the N(2)OR across the membrane. Sequencing of environmental clones of the previously undetected nosZ lineage in various environments showed that it is widespread and diverse. Using quantitative PCR, we demonstrate that this clade was most often at least as abundant as the other, thereby more than doubling the known extent of the overall N(2)O-reducing community in the environment. Furthermore, we observed that the relative abundance of nosZ from either clade varied among habitat types and environmental conditions. Our results indicate a physiological dichotomy in the diversity of N(2)O-reducing microorganisms, which might be of importance for understanding the relationship between the diversity of N(2)O-reducing microorganisms and N(2)O reduction in different ecosystems.
Project description:Stratospheric ozone has begun to recover in Antarctica since the implementation of the Montreal Protocol. However, the effects of ultraviolet (UV) radiation on tundra greenhouse gas fluxes are rarely reported for Polar Regions. In the present study, tundra N2O and CH4 fluxes were measured under the simulated reduction of UV radiation in maritime Antarctica over the last three-year summers. Significantly enhanced N2O and CH4 emissions occurred at tundra sites under the simulated reduction of UV radiation. Compared with the ambient normal UV level, a 20% reduction in UV radiation increased tundra emissions by an average of 8??g N2O m-2 h-1 and 93??g CH4 m-2 h-1, whereas a 50% reduction in UV radiation increased their emissions by an average of 17??g N2O m-2 h-1 and 128??g CH4 m-2 h-1. No statistically significant correlation (P?>?0.05) was found between N2O and CH4 fluxes and soil temperature, soil moisture, total carbon, total nitrogen, NO3--N and NH4+-N contents. Our results confirmed that UV radiation intensity is an important factor affecting tundra N2O and CH4 fluxes in maritime Antarctica. Exclusion of the effects of reduced UV radiation might underestimate their budgets in Polar Regions with the recovery of stratospheric ozone.
Project description:Mood disorders such as major depressive disorder and bipolar disorder--and their consequent effects on the individual and society--are among the most disabling and costly of all medical illnesses. Although a number of antidepressant treatments are available in clinical practice, many patients still undergo multiple and lengthy medication trials before experiencing relief of symptoms. Therefore a tremendous need exists to improve current treatment options and to facilitate more rapid, successful treatment in patients suffering from the deleterious neurobiological effects of ongoing depression. Toward that end, ongoing research is exploring the identification of biomarkers that might be involved in prevention, diagnosis, treatment response, severity, or prognosis of depression. Biomarkers evaluating treatment response will be the focus of this review, given the importance of providing relief to patients in a more expedient and systematic manner. A novel approach to developing such biomarkers of response would incorporate interventions with a rapid onset of action--such as sleep deprivation or intravenous drugs (e.g., ketamine or scopolamine). This alternative translational model for new treatments in psychiatry would facilitate shorter studies, improve feasibility, and increase higher compound throughput testing for these devastating disorders.
Project description:Nitrous oxide is a powerful greenhouse gas whose atmospheric growth rate has accelerated over the past decade. Most anthropogenic N2O emissions result from soil N fertilization, which is converted to N2O via oxic nitrification and anoxic denitrification pathways. Drought-affected soils are expected to be well oxygenated; however, using high-resolution isotopic measurements, we found that denitrifying pathways dominated N2O emissions during a severe drought applied to managed grassland. This was due to a reversible, drought-induced enrichment in nitrogen-bearing organic matter on soil microaggregates and suggested a strong role for chemo- or codenitrification. Throughout rewetting, denitrification dominated emissions, despite high variability in fluxes. Total N2O flux and denitrification contribution were significantly higher during rewetting than for control plots at the same soil moisture range. The observed feedbacks between precipitation changes induced by climate change and N2O emission pathways are sufficient to account for the accelerating N2O growth rate observed over the past decade.
Project description:More than two-thirds of the powerful greenhouse gas nitrous oxide (N2O) emissions from soils can be attributed to microbial denitrification and nitrification processes. Bacterial denitrification reactions are catalyzed by the periplasmic (Nap) or membrane-bound (Nar) nitrate reductases, nitrite reductases (NirK/cd 1Nir), nitric oxide reductases (cNor, qNor/ CuANor), and nitrous oxide reductase (Nos) encoded by nap/nar, nir, nor and nos genes, respectively. Rhizobium etli CFN42, the microsymbiont of common bean, is unable to respire nitrate under anoxic conditions and to perform a complete denitrification pathway. This bacterium lacks the nap, nar and nos genes but contains genes encoding NirK and cNor. In this work, we demonstrated that R. etli is able to grow with nitrate as the sole nitrogen source under aerobic and microoxic conditions. Genetic and functional characterization of a gene located in the R. etli chromosome and annotated as narB demonstrated that growth under aerobic or microoxic conditions with nitrate as nitrogen source as well as nitrate reductase activity requires NarB. In addition to be involved in nitrate assimilation, NarB is also required for NO and N2O production by NirK and cNor, respectively, in cells grown microoxically with nitrate as the only N source. Furthermore, β-glucuronidase activity from nirK::uidA and norC::uidA fusions, as well as NorC expression and Nir and Nor activities revealed that expression of nor genes under microoxic conditions also depends on nitrate reduction by NarB. Our results suggest that nitrite produced by NarB from assimilatory nitrate reduction is detoxified by NirK and cNor denitrifying enzymes that convert nitrite into NO which in turn is reduced to N2O, respectively.
Project description:Nitrous oxide (N2O), a potent greenhouse gas in the atmosphere, is produced mostly from aquatic ecosystems, to which algae substantially contribute. However, mechanisms of N2O production by photosynthetic organisms are poorly described. Here we show that the green microalga Chlamydomonas reinhardtii reduces NO into N2O using the photosynthetic electron transport. Through the study of C. reinhardtii mutants deficient in flavodiiron proteins (FLVs) or in a cytochrome p450 (CYP55), we show that FLVs contribute to NO reduction in the light, while CYP55 operates in the dark. Both pathways are active when NO is produced in vivo during the reduction of nitrites and participate in NO homeostasis. Furthermore, NO reduction by both pathways is restricted to chlorophytes, organisms particularly abundant in ocean N2O-producing hot spots. Our results provide a mechanistic understanding of N2O production in eukaryotic phototrophs and represent an important step toward a comprehensive assessment of greenhouse gas emission by aquatic ecosystems.
Project description:A large variety of aquatic animals was found to emit the potent greenhouse gas nitrous oxide when nitrate was present in the environment. The emission was ascribed to denitrification by ingested bacteria in the anoxic animal gut, and the exceptionally high N(2)O-to-N(2) production ratio suggested delayed induction of the last step of denitrification. Filter- and deposit-feeding animal species showed the highest rates of nitrous oxide emission and predators the lowest, probably reflecting the different amounts of denitrifying bacteria in the diet. We estimate that nitrous oxide emission by aquatic animals is quantitatively important in nitrate-rich aquatic environments like freshwater, coastal marine, and deep-sea ecosystems. The contribution of this source to overall nitrous oxide emission from aquatic environments might further increase because of the projected increase of nitrate availability in tropical regions and the numeric dominance of filter- and deposit-feeders in eutrophic ecosystems.