Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and “Astrocyte-Cytokine-NMDAR-neuron” pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.
Low phosphorus (P) availability and salt stress are two major constraints for maize ( Zea mays L.) growth in north China. A combination of salinity and high P rather than low P is more detrimental to the growth of maize. However, little is known about the mechanisms by which P nutrition modifies the salt tolerance and P uptake of maize. The present study aimed to investigate the combined effects of salinity and P on maize growth and P uptake, and to address the physiological mechanisms of salt tolerance influenced by P availability in maize. Seedlings of a local maize cultivar XY335 were grown hydroponically for 35 days under low (5 μM) or sufficient P supply (200 μM) with or without 100 mM NaCl. Root morphological traits, tissue mass density, leaf osmolytes (sugars and proline) accumulation, and Na + /K + ratio were measured to allow evaluation of the combined effects of salinity and P on maize growth and P uptake. Both P deficiency and salinity markedly reduced the growth of maize. However, P deficiency had a more pronounced effect on shoot growth while salinity affected root growth more prominently. Combined effects of P deficiency and salinity on total root length, root surface area, and average root diameter were similar to that of plants grown under salt stress. The combination of P deficiency and salinity treatments had a more pronounced effect on tissue mass density, leaf proline and soluble sugars compared to individual treatment of either low P or NaCl. When exposed to salt stress, maize plants of sufficient P accumulated greater amount of Na + than those under P deficit, but similar amounts of K + were observed between the two P treatments. Salt stress significantly increased shoot P concentration of maize with sufficient P ( P < 0.01), but not for P-deficient plants. In sum, shoots and roots of maize exhibited different responses to P deficiency and salinity, with more marked effect of P deficiency on shoots and of salinity on roots. P deficiency improved salt tolerance of maize plants, which was associated with the increase of tissue mass density, accumulation of osmolytes, reduction of Na + accumulation, and selective absorption of K + over Na + .
-The study of sustainable land use is complex and long-term experiments are required for a better understanding of the processes of carbon stabilization. Objectives were (i) to describe for four long-term experiments the effects of fertilization and soil management on crop yields and the dynamics of soil organic carbon (SOC) and total N, and (ii) to discuss the usefulness of models for a better understanding of the underlying processes. Data of soil organic carbon and total N of four long-term experiments in Germany and China which studied the effect of fertilization (Bad Lauchstädt, Darmstadt) and tillage (Göttingen, Quzhou) were evaluated and soil organic carbon fractionation was carried out. The Rothamsted Carbon Model was used for a description and prediction of soil organic carbon dynamics as affected by fertilization and tillage in Bad Lauchstädt and Quzhou. The type of fertilizer added at common rates -either mineral N or farmyard manure -affected the crop yields only slightly, with slightly lower yields after manure application compared with mineral N fertilization. For both fertilization trials, manure applications at common rates had beneficial effects on soil organic carbon stocks in the labile pool (turnover time estimated as <10 years) and to a greater extent in the intermediate pool (turnover time estimated to be in the range of 10 to 100 years). A comparison of the effects of conventional tillage, reduced tillage and no-tillage carried out in Göttingen and Quzhou indicated only small differences in crop yields. Reduced tillage in Göttingen resulted in an increased C storage in the surface soil and C was mainly located in the mineral-associated organic matter fraction and in water-stable macro-aggregates (>0.25 mm). For Quzhou, no-tillage and conventional tillage had similar effects on total C stocks, with a greater spatial variability in soil organic carbon stocks in the no-tillage plots. Modeling required site-specific calibrations for the stock of inert organic matter for each of the sites, indicating that not all carbon stabilization processes are included in the model and that application of a model to a new site may also need site-specific adjustments before it can be used for predictions. After site-specific calibration, however, model predictions for the remaining treatments were generally accurate for the fertilization and tillage trials, which emphasizes the importance of temperature, moisture, soil cover and clay content on the decomposition dynamics of soil organic carbon and the significance of amounts and quality of carbon inputs in the soil for maintaining or increasing soil organic carbon stocks in arable soils.soil organic matter / C dynamics / Rothamsted carbon model / tillage / fertilization / soil organic carbon (SOC)
Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron population with metabolic intermediates to meet energy requirements under conditions of increased demand. Disruption of this astroglial-neuron metabolic coupling pathway may contribute to epileptogenesis. We measured MCT4 expression in temporal lobe epileptic foci excised from patients with intractable epilepsy and in rats injected with pilocarpine, an animal model of temporal lobe epilepsy (TLE). Cortical MCT4 expression levels were significantly lower in TLE patients compared with controls, due at least partially to MCT4 promoter methylation. Expression of MCT4 also decreased progressively in pilocarpine-treated rats from 12 h to 14 days post-administration. Underexpression of MCT4 in cultured astrocytes induced by a short hairpin RNA promoted apoptosis. Knockdown of astrocyte MCT4 also suppressed excitatory amino acid transporter 1 (EAAT1) expression. Reduced MCT4 and EAAT1 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate.
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