Effect of neuregulin-1 on histopathological and functional outcome after controlled cortical impact in mice.

Neuregulin-1 is a pleiotropic endogenous growth factor that is neuroprotective in experimental models of cerebral ischemia. We tested the hypothesis that pretreatment with neuregulin-1 would be similarly protective after traumatic brain injury in mice. Mice were administered neuregulin-1 or equal amounts of vehicle intravenously immediately before controlled cortical impact. Injured mice were subjected to motor and cognitive testing, and brain tissue loss was quantitated at 4 weeks. Compared to vehicle, pretreatment with neuregulin-1 had no effect on brain tissue loss, motor function, or acquisition of a spatial learning task. However, neuregulin-1 treated mice showed improved retention of spatial memory versus vehicle-treated mice in subsequent probe trials (p<0.05). These proof-of-principle data suggest that neuregulin-1 may improve some functional outcomes after brain trauma. Further studies are therefore warranted to more carefully explore molecular mechanisms, dose-responses, and relationships between morphological outcome and long-term recovery.

Wheat ROP proteins modulate defense response through lignin metabolism.

ROP is a subfamily of small GTP-binding proteins that uniquely exist in plants. It acts as versatile molecular switches that regulate various developmental processes. Some ROP proteins are also reported to affect defense responses, although their exact mechanism is not fully understood. Herein, ROP members in wheat were mined; the functions of three wheat ROP proteins were studied. RT-PCR results showed that the expression of TaRac1 was rapidly and strongly induced after leaf rust infection. TaRac1 interacted with TaCCR in yeast-hybridization assay. The overexpression of TaRac1 in tobacco promoted CCR and CAD gene expression, increased the total lignin content and sinapyl lignin proportion, and then enhanced resistance to tobacco black shank and bacterial wilt diseases. In contrast, TaRac3 and TaRac4 did not show to interact with TaCCR. Furthermore, the overexpression of TaRac3 and TaRac4 did not increase lignin gene expression and lignin accumulation either. Unlike TaRac1, the overexpression of TaRac3 increased susceptibility to both black shank and bacterial wilt pathogens, while overexpression of TaRac4 showed no effect on disease resistance but promoted the root growth in tobacco seedling. These data collectively suggest that TaRac1 in Group II is mainly involved in regulating lignin metabolism which, in turn, responsible for the observed roles in pathogen resistance. TaRac3 and TaRac4 have the minor roles in defense response but may act on regulation in plant developmental processes. These results shed light on the complexity and diverse function of ROP in plant defense pathway.

TaMYB4 cloned from wheat regulates lignin biosynthesis through negatively controlling the transcripts of both cinnamyl alcohol dehydrogenase and cinnamoyl-CoA reductase genes.

The subgroup 4 of R2R3-MYB transcription factors has been proposed as repressors regulating the phenylpropanoid pathway. Here, we report a cDNA encoding a subgroup 4 R2R3-MYB factor from wheat, designated as TaMYB4. A phylogenetic analysis showed that TaMYB4 is in a subclade that is specific to monocot plants. The TaMYB4 gene was highly expressed in stem and root tissues. In vitro binding analysis in yeast cells showed TaMYB4 interacted with OsCAD2 promoter characterized by an AC-II element that has been considered as the MYB-binding site in lignin biosynthetic genes. The overexpression of TaMYB4 in transgenic tobacco led to transcriptional reduction of both cinnamyl alcohol dehydrogenase (CAD) and cinnamoyl-CoA reductase (CCR) genes involved in the lignin biosynthesis. Enzymatic assay showed reduction of CAD and CCR activities in the transgenic tobacco plants that substantially decreased the levels of total lignin but increased it's ratio of S/G. In addition, the total flavonoid content was increased in transgenic tobacco leaves, suggesting that the overexpression of TaMYB4 likely led to a redirection of the metabolic flux from the lignin pathway to the flavonoid pathway. These data suggest that TaMYB4 negatively regulates the lignin biosynthesis in wheat.

Distribution of downstream regulatory element antagonist modulator (DREAM) in rat spinal cord and upregulation of its expression during inflammatory pain.

A previous knockout study revealed the critical role of downstream regulatory element antagonist modulator (DREAM) in pain processing in the spinal cord by transcriptional regulation of prodynorphin (PPD) gene. Here, we report that, in contrast to the nuclear localization of other transcription factors, DREAM showed a punctate staining pattern in rat spinal dorsal horn in immunofluorescent analysis, with a membrane localization profile in some neurons and its expression accumulated in the inner zone of lamina II. In an inflammatory pain model induced by complete Freund's adjuvant (CFA) injection, we used Western blot analysis and detected transient upregulation of DREAM in the nuclear fraction of ipsilateral spinal dorsal horn at 2 h and 6 h post-injection, and a slow upregulation in the membrane fraction for 7 days. These studies suggest that DREAM might have other roles in pain modulation in the spinal cord in addition to its well-known role as a transcriptional repressor.