Melatonin mitigates traumatic brain injury-induced depression-like behaviors through HO-1/CREB signal in rats.

In addition to significant antioxidant properties, melatonin exhibits neuroprotective effects against various neurological diseases including traumatic brain injury (TBI) and ischemic stroke. Several potential mechanisms have been reported in the neuroprotection of melatonin among patients with TBI. Notably, the heme oxygenase-1 (HO-1)/cAMP response element-binding protein (CREB) signaling pathway is implicated in the development of a depressive state. Moreover, the activity of CREB in the nucleus accumbens (NAc) participates in reward and motivation, further contributing to depression induced by TBI. This study aims to explore whether melatonin could mitigate TBI-induced depression by activating of HO-1/CREB signal in a rodent model of weight-drop. As a consequence, melatonin (10 mg/kg) attenuated TBI-induced elevated immobility time in the force swim test, decreased time spent sniffing the novel rat in 3-chambered social test, and downregulated phosphorylated CERB in the NAc. However, a special inhibitor of HO-1 (SnPP) via intracerebroventricular injection partially reversed the neuroprotective effects of melatonin. Furthermore, melatonin decreased the number of summarized intersects in the astrocyte, A1-type astrocytes, IL-6-positive astrocytes in the NAc after TBI exposure, nevertheless, these changes could partially be restored by SnPP. Therefore, our findings demonstrate a novel neuroprotective mechanism for melatonin against TBI which can be a potential neuroprotective agent for the treatment of TBI-induced depression.

Melatonin alleviates traumatic brain injury-induced anxiety-like behaviors in rats: Roles of the protein kinase A/cAMP-response element binding signaling pathway.

Melatonin is a hormone produced by the pineal gland. Given its capabilities of neuroprotection and low neurotoxicity, melatonin could be a therapeutic strategy for traumatic brain injury (TBI). The present study was conducted to determine the neuroprotective effects of melatonin on TBI-induced anxiety and the possible molecular mechanism. Rats were randomly divided into seven groups. The rodent model of TBI was established using the weight-drop method. Melatonin was administered by intraperitoneal injection at a dose of 10 mg/kg after TBI. H89 (0.02 mg/kg), a special protein kinase A (PKA) inhibitor, or dibutyryl-cyclic adenosine monophosphate (cAMP; 0.1 mg/kg), an activator of PKA, were administered by stereotactic injection of the brain to evaluate the roles of PKA and cAMP-response element-binding protein (CREB) in melatonin-related mood regulation, respectively. At 30 days post-TBI, the changes in anxiety-like behaviors in rats were measured using the open field and elevated plus maze tests. At 24 h post-TBI, the number of activated astrocytes and neuronal apoptosis were evaluated using immunofluorescence assay. The expression levels of inflammatory cytokines (TNF-α and IL-6) in the amygdala were measured using an enzyme-linked immunosorbent assay. The expression levels of PKA, phosphorylated (p)-PKA, CREB, p-CREB, NF-κB and p-NF-κB in the amygdala were detected using western blotting. It was revealed that melatonin partially reversed TBI-induced anxiety-like behavior in rats, and decreased the number of activated astrocytes and neuronal apoptosis in the amygdala induced by TBI. H89 partially blocked the neuroprotective effects of melatonin; while dibutyryl-cAMP not only reduced the H89-induced emotional disturbance but also enhanced the protective effects of melatonin against TBI. Overall, melatonin can alleviate TBI-induced anxiety-like behaviors in rats. Moreover, the underlying mechanism may be associated with the activation of the PKA/CREB signaling pathway.

Androgen is responsible for enhanced susceptibility of melatonin against traumatic brain injury in females.

BACKGROUND: Numerous publications have demonstrated that melatonin administration is associated with mortality reduction and improvement in neurological outcomes after traumatic brain injury (TBI). However, there are significant sex differences in several diseases associated with melatonin. We aimed to determine whether androgen was responsible for enhanced susceptibility of melatonin against TBI in females, as well as potential molecular mechanisms. METHODS: Weight-drop was used to establish a rodent model of TBI. Melatonin (10 mg/kg) and testosterone (1 mg/kg) were administered three times every day for three days after TBI using subcutaneous injection, respectively. Seven days after TBI, an open field assay was used to evaluate locomotor and exploratory activities. Neuronal amount, neuronal apoptosis, and expression of phosphorylated extracellularly regulated protein kinases 1/2 (ERK1/2), c-jun N-terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (p38MAPK) in neurons were assessed using immunofluorescence assay seven days after TBI. The expression of caspase-3, Bax, and Bcl-2 in the frontal cortex was detected using western blot. RESULTS: Compared with female rats, melatonin administration exhibited more neuroprotective effects (including improved locomotor and exploratory activities, elevated neuronal amount, and reduced neuronal apoptosis) in male rats exposed to TBI. Moreover, testosterone significantly improved locomotor and exploratory activities, elevated neuronal amount, decreased neuronal apoptosis, downregulated phosphorylation of JNK1/2- and p38MAPK-positive neurons, but upregulated phosphorylation of ERK1/2-positive neurons in the frontal cortex, and reduced the expressions of cleaved caspase-3, Bax, but increased Bcl-2 expressions in female rats exposed to TBI. CONCLUSIONS: Androgen was responsible for the enhanced susceptibility to TBI under melatonin supplementation in females through a mechanism that may be associated with MAPK pathway regulation.

Antifungal activity of the osthol derivative JS-B against Phytophthora capsici.

JS-B (C(12)H(10)O(3)) is a derivative compound of osthol. The antifungal properties of JS-B were tested against 10 economically important plant pathogens. JS-B was effective in inhibiting the mycelial growth of Phytophthora capsici, and its inhibition on different stages of the life cycle of P. capsici was observed. The 50% effective concentration (EC(50)) of JS-B on mycelial dry weight and zoospore germination of P. capsici was 43.74 and 86.03 microg/ml, respectively. The rupture of released zoospores induced by JS-B was reduced by the addition of 100 mM glucose. The ultrastructural study showed that JS-B caused destruction of most of the mitochondrions, the concentration of cell nuclear, and the existing vesicles. When compared with dimethomorph, the activity of JS-B on P. capsici was determined under pot conditions. The result showed that JS-B has a curative effect on pepper blight.

Efficacy of osthol, a potent coumarin compound, in controlling powdery mildew caused by Sphaerotheca fuliginea.

The efficacy of osthol, a natural coumarin compound, in controlling powdery mildew was evaluated in 2004-2005 in Anhui and Hebei Provinces of China. In both years, the treatments (osthol 15.0 and 18.0 g ai ha(- 1)) showed a stable control efficiency of 75.42, 81.24% and 76.36, 84.84%, respectively, at the Institutes of Plant Protection of Hebei Academy of Agricultural Sciences. In field experiments, osthol was as effective as difenoconazole in controlling powdery mildew and was more effective than triadimefon against Sphaerotheca fuliginea. Protection was expressed as a significant reduction (up to 87% compared with the control) in the mildewed leaf area in young pumpkin plants. Osthol strongly inhibited spore germination and mycelial growth of S. fuliginea in vitro, damaged the cell wall and the organelles of the pathogen. At 48 h after incubation, 50 microg ml(- 1) osthol could completely inhibit spore germination. These findings suggested that the effect of osthol on powdery mildew may be associated with the direct fungitoxic property against the pathogen. We conclude that osthol would be an attractive natural compound for practical agronomic use against powdery mildew.

[QTL analysis for rice stripe disease resistance gene using recombinant inbred lines (RILs) derived from crossing of Kinmaze and DV85].

Rice stripe disease transmitted by small brown planthopper (Laodelphax striatellus Fall.) is one of the most serious viral diseases in East Asia. The disease is severely epidemic in most rice growing areas where the main cultivars are susceptible or moderately susceptible to rice stripe virus. In this research, a recombinant inbred lines (RILs) population of 81 lines derived from a cross of Kinmaze (japonica)/DV85(indica) by the single seed descent method was used to detect quantitative trait loci (QTL) conferring resistance to rice stripe virus(RSV). The response of the two parents and 81 RILs to RSV were investigated by inoculating seedlings with viruliferous small brown planthopper insects, and scored by the disease rate index. The quantitative trait loci for rice stripe disease resistance were analyzed by QTL Cartographer software. Three QTL controlling RSV resistance were detected on chromosomes 1, 7 and 11, respectively. Individual QTL accounted for 19.8%-30.9% of the phenotypic variance in the RILs population. The direction of the additive gene effects at two loci qStv7 and qStv11 coincided with that predicted by phenotypes of the parents. At these two loci, the DV85 alleles increased the resistance to RSV, while at qStv1, the Kinmaze alleles increased the resistance to RSV.