Publications by authors named "Xiaolan Rao"

31 Publications

Melatonin improves brain function in a model of chronic Gulf War Illness with modulation of oxidative stress, NLRP3 inflammasomes, and BDNF-ERK-CREB pathway in the hippocampus.

Redox Biol 2021 07 22;43:101973. Epub 2021 Apr 22.

Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, TX, USA. Electronic address:

Persistent cognitive and mood dysfunction is the primary CNS symptom in veterans afflicted with Gulf War Illness (GWI). This study investigated the efficacy of melatonin (MEL) for improving cognitive and mood function with antioxidant, antiinflammatory, and pro-cognitive effects in a rat model of chronic GWI. Six months after exposure to GWI-related chemicals and stress, rats were treated with vehicle or MEL (5, 10, 20, 40, and 80 mg/kg) for eight weeks. Behavioral tests revealed cognitive and mood dysfunction in GWI rats receiving vehicle, which were associated with elevated oxidative stress, reduced NRF2, catalase and mitochondrial complex proteins, astrocyte hypertrophy, activated microglia with NLRP3 inflammasomes, elevated proinflammatory cytokines, waned neurogenesis, and synapse loss in the hippocampus. MEL at 10 mg/kg alleviated simple and associative recognition memory dysfunction and anhedonia, along with reduced oxidative stress, enhanced glutathione and complex III, and reduced NLRP3 inflammasomes, IL-18, TNF-α, and IFN-γ. MEL at 20 mg/kg also normalized NRF2 and catalase and increased microglial ramification. MEL at 40 mg/kg, in addition, reduced astrocyte hypertrophy, activated microglia, NF-kB-NLRP3-caspase-1 signaling, IL-1β, MCP-1, and MIP-1α. Moreover, MEL at 80 mg/kg activated the BDNF-ERK-CREB signaling pathway, enhanced neurogenesis and diminished synapse loss in the hippocampus, and improved a more complex hippocampus-dependent cognitive function. Thus, MEL therapy is efficacious for improving cognitive and mood function in a rat model of chronic GWI, and MEL's effect was dose-dependent. The study provides the first evidence of MEL's promise for alleviating neuroinflammation and cognitive and mood impairments in veterans with chronic GWI.
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http://dx.doi.org/10.1016/j.redox.2021.101973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105671PMC
July 2021

Growth-defense trade-offs and yield loss in plants with engineered cell walls.

New Phytol 2021 07 4;231(1):60-74. Epub 2021 May 4.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, 1155 Union Circle #311428, Denton, TX, 76203, USA.

As a major component of plant secondary cell walls, lignin provides structural integrity and rigidity, and contributes to primary defense by providing a physical barrier to pathogen ingress. Genetic modification of lignin biosynthesis has been adopted to reduce the recalcitrance of lignified cell walls to improve biofuel production, tree pulping properties and forage digestibility. However, lignin-modification is often, but unpredictably, associated with dwarf phenotypes. Hypotheses suggested to explain this include: collapsed vessels leading to defects in water and solute transport; accumulation of molecule(s) that are inhibitory to plant growth or deficiency of metabolites that are critical for plant growth; activation of defense pathways linked to cell wall integrity sensing. However, there is still no commonly accepted underlying mechanism for the growth defects. Here, we discuss recent data on transcriptional reprogramming in plants with modified lignin content and their corresponding suppressor mutants, and evaluate growth-defense trade-offs as a factor underlying the growth phenotypes. New approaches will be necessary to estimate how gross changes in transcriptional reprogramming may quantitatively affect growth. Better understanding of the basis for yield drag following cell wall engineering is important for the biotechnological exploitation of plants as factories for fuels and chemicals.
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http://dx.doi.org/10.1111/nph.17383DOI Listing
July 2021

Dissecting the transcriptional regulation of proanthocyanidin and anthocyanin biosynthesis in soybean (Glycine max).

Plant Biotechnol J 2021 Jul 15;19(7):1429-1442. Epub 2021 Feb 15.

Department of Biological Sciences, BioDiscovery Institute, University of North Texas, Denton, TX, USA.

Proanthocyanidins (PAs), also known as condensed tannins, are plant natural products that are beneficial for human and livestock health. As one of the largest grown crops in the world, soybean (Glycine max) is widely used as human food and animal feed. Many cultivated soybeans with yellow seed coats lack PAs or anthocyanins, although some soybean cultivars have coloured seed coats that contain these compounds. Here, we analyse the transcriptional control of PA and anthocyanin biosynthesis in soybean. Ectopic expression of the transcription factors (TFs) GmTT2A, GmTT2B, GmMYB5A or R in soybean hairy roots induced the accumulation of PAs (primarily in phloem tissues) or anthocyanins and led to up-regulation of 1775, 856, 1411 and 1766 genes, respectively, several of which encode enzymes involved in PA biosynthesis. The genes regulated by GmTT2A and GmTT2B partially overlapped, suggesting conserved but potentially divergent roles for these two TFs in regulating PA accumulation in soybean. The two key enzymes anthocyanidin reductase and leucoanthocyanidin reductase were differentially upregulated, by GmTT2A/GmTT2B and GmMYB5A, respectively. Transgenic soybean plants overexpressing GmTT2B or MtLAP1 (a proven up-regulator of the upstream reactions for production of precursors for PA biosynthesis in legumes) showed increased accumulation of PAs and anthocyanins, respectively, associated with transcriptional reprogramming paralleling the RNA-seq data collected in soybean hairy roots. Collectively, our results show that engineered PA biosynthesis in soybean exhibits qualitative and spatial differences from the better-studied model systems Arabidopsis thaliana and Medicago truncatula, and suggest targets for engineering PAs in soybean plants.
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http://dx.doi.org/10.1111/pbi.13562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313137PMC
July 2021

Abscisic acid regulates secondary cell-wall formation and lignin deposition in through phosphorylation of NST1.

Proc Natl Acad Sci U S A 2021 02;118(5)

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, TX 76203;

Plant secondary cell-wall (SCW) deposition and lignification are affected by both seasonal factors and abiotic stress, and these responses may involve the hormone abscisic acid (ABA). However, the mechanisms involved are not clear. Here we show that mutations that limit ABA synthesis or signaling reduce the extent of SCW thickness and lignification in through the core ABA-signaling pathway involving SnRK2 kinases. SnRK2.2. 3 and 6 physically interact with the SCW regulator NAC SECONDARY WALL THICKENING PROMOTING FACTOR 1 (NST1), a NAC family transcription factor that orchestrates the transcriptional activation of a suite of downstream SCW biosynthesis genes, some of which are involved in the biosynthesis of cellulose and lignin. This interaction leads to phosphorylation of NST1 at Ser316, a residue that is highly conserved among NST1 proteins from dicots, but not monocots, and is required for transcriptional activation of downstream SCW-related gene promoters. Loss of function of NST1 in the mutant background results in lack of SCWs in the interfascicular fiber region of the stem, and the Ser316Ala mutant of NST1 fails to complement this phenotype and ABA-induced lignin pathway gene expression. The discovery of NST1 as a key substrate for phosphorylation by SnRK2 suggests that the ABA-mediated core-signaling cascade provided land plants with a hormone-modulated, competitive desiccation-tolerance strategy allowing them to differentiate water-conducting and supporting tissues built of cells with thicker cell walls.
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http://dx.doi.org/10.1073/pnas.2010911118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865148PMC
February 2021

Metformin treatment in late middle age improves cognitive function with alleviation of microglial activation and enhancement of autophagy in the hippocampus.

Aging Cell 2021 02 14;20(2):e13277. Epub 2021 Jan 14.

Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, TX, USA.

Metformin, a drug widely used for treating diabetes, can prolong the lifespan in several species. Metformin also has the promise to slow down age-related cognitive impairment. However, metformin's therapeutic use as an anti-aging drug is yet to be accepted because of conflicting animal and human studies results. We examined the effects of metformin treatment in late middle age on cognitive function in old age. Eighteen-month-old male C57BL6/J mice received metformin or no treatment for 10 weeks. A series of behavioral tests revealed improved cognitive function in animals that received metformin. Such findings were evident from a better ability for pattern separation, object location, and recognition memory function. Quantification of microglia revealed that metformin treatment reduced the incidence of pathological microglial clusters with alternative activation of microglia into an M2 phenotype, displaying highly ramified processes in the hippocampus. Metformin treatment also seemed to reduce astrocyte hypertrophy. Additional analysis demonstrated that metformin treatment in late middle age increased adenosine monophosphate-activated protein kinase activation, reduced proinflammatory cytokine levels, and the mammalian target of rapamycin signaling, and enhanced autophagy in the hippocampus. However, metformin treatment did not alter neurogenesis or synapses in the hippocampus, implying that improved cognitive function with metformin did not involve enhanced neurogenesis or neosynaptogenesis. The results provide new evidence that metformin treatment commencing in late middle age has promise for improving cognitive function in old age. Modulation of microglia, proinflammatory cytokines, and autophagy appear to be the mechanisms by which metformin facilitated functional benefits in the aged brain.
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http://dx.doi.org/10.1111/acel.13277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884047PMC
February 2021

Lipophilic signals lead to organ-specific gene expression changes in seedlings.

Plant Direct 2020 Jul 15;4(7):e00242. Epub 2020 Jul 15.

BioDiscovery Institute and Department of Biological Sciences University of North Texas Denton TX USA.

In plants, -acylethanolamines (NAEs) are most abundant in desiccated seeds and their levels decline during germination and early seedling establishment. However, endogenous NAE levels rise in seedlings when ABA or environmental stress is applied, and this results in an inhibition of further seedling development. When the most abundant, polyunsaturated NAEs of linoleic acid (18:2) and linolenic acid (18:3) were exogenously applied, seedling development was affected in an organ-specific manner. NAE 18:2 primarily affected primary root elongation and NAE 18:3 primarily affected cotyledon greening and expansion and overall seedling growth. The molecular components and signaling mechanisms involved in this pathway are not well understood. In addition, the bifurcating nature of this pathway provides a unique system in which to study the spatial aspects and interaction of these lipid-specific and organ-targeted signaling pathways. Using whole transcriptome sequencing (RNA-seq) and differential expression analysis, we identified early (1-3 hr) transcriptional changes induced by the exogenous treatment of NAE 18:2 and NAE 18:3 in cotyledons, roots, and seedlings. These two treatments led to a significant enrichment in ABA-response and chitin-response genes in organs where the treatments led to changes in development. In seedlings, NAE 18:2 treatment led to the repression of genes involved in cell wall biogenesis and organization in roots and seedlings. In addition, cotyledons, roots, and seedlings treated with NAE 18:3 also showed a decrease in transcripts that encode proteins involved in growth processes. NAE 18:3 also led to changes in the abundance of transcripts involved in the modulation of chlorophyll biosynthesis and catabolism in cotyledons. Overall, NAE 18:2 and NAE 18:3 treatment led to lipid-type and organ-specific gene expression changes that include overlapping and non-overlapping gene sets. These data will provide future, rich opportunities to examine the genetic pathways involved in transducing early signals into downstream physiological changes in seedling growth.
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http://dx.doi.org/10.1002/pld3.242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403840PMC
July 2020

SINGLE FLOWER TRUSS and SELF-PRUNING signal developmental and metabolic networks to guide cotton architectures.

J Exp Bot 2020 10;71(19):5911-5923

BioDiscovery Institute, Department of Biological Sciences, University of North Texas, Denton, TX, USA.

Patterns of indeterminate and determinate growth specify plant architecture and influence crop productivity. In cotton (Gossypium hirsutum), SINGLE FLOWER TRUSS (SFT) stimulates the transition to flowering and determinate growth, while its closely related antagonist SELF-PRUNING (SP) maintains meristems in indeterminate states to favor vegetative growth. Overexpressing GhSFT while simultaneously silencing GhSP produces highly determinate cotton with reduced foliage and synchronous fruiting. These findings suggest that GhSFT, GhSP, and genes in these signaling networks hold promise for enhancing 'annualized' growth patterns and improving cotton productivity and management. To identify the molecular programs underlying cotton growth habits, we used comparative co-expression networks, differential gene expression, and phenotypic analyses in cotton varieties expressing altered levels of GhSFT or GhSP. Using multiple cotton and tomato datasets, we identified diverse genetic modules highly correlated with SFT or SP orthologs which shared related Gene Ontologies in different crop species. Notably, altering GhSFT or GhSP levels in cotton affected the expression of genes regulating meristem fate and metabolic pathways. Further phenotypic analyses of gene products involved in photosynthesis, secondary metabolism, and cell wall biosynthesis showed that early changes in GhSFT and GhSP levels profoundly impacted later development in distal tissues. Identifying the molecular underpinnings of GhSFT and GhSP activities emphasizes their broad actions in regulating cotton architecture.
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http://dx.doi.org/10.1093/jxb/eraa338DOI Listing
October 2020

Editorial: Regulation of and by the Plant Cell Wall.

Front Plant Sci 2020 29;11:513. Epub 2020 Apr 29.

Department of Biology, The Pennsylvania State University, University Park, PA, United States.

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http://dx.doi.org/10.3389/fpls.2020.00513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201071PMC
April 2020

Alteration of iron responsive gene expression in Arabidopsis glutaredoxin loss of function plants with or without iron stress.

Plant Signal Behav 2020 06 30;15(6):1758455. Epub 2020 Apr 30.

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA.

Iron (Fe) is a mineral nutrient and a metal cofactor essential for plants. Iron limitation can have detrimental effects on plant growth and development, while excess iron inside plant cells leads to oxidative damage. As a result, plants have evolved complex regulatory networks to respond to fluctuations in cellular iron concentrations. The mechanisms that regulate these responses however, are not fully understood. Heterologous expression of an monothiol glutaredoxin S17 (GRXS17) suppresses the over-accumulation of iron in the Grx3/Grx4 mutant and disruption of causes plant sensitivity to exogenous oxidants and iron deficiency stress. GRXS17 may act as an important regulator in the plant's ability to respond to iron deficiency stress and maintain redox homeostasis. Here, we extend this investigation by analyzing iron-responsive gene expression of the Fer-like iron deficiency-induced transcription factor (FIT) network (, and ) and the bHLH transcription factor POPEYE (PYE) network (, and ) in KO plants and wildtype controls grown under iron sufficiency and deficiency conditions. Our findings suggest that GRXS17 is required for tolerance to iron deficiency, and plays a negative regulatory role under conditions of iron sufficiency.
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http://dx.doi.org/10.1080/15592324.2020.1758455DOI Listing
June 2020

ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE 1 (ADPG1) releases latent defense signals in stems with reduced lignin content.

Proc Natl Acad Sci U S A 2020 02 23;117(6):3281-3290. Epub 2020 Jan 23.

BioDiscovery Institute, University of North Texas, Denton, TX 76203;

There is considerable interest in engineering plant cell wall components, particularly lignin, to improve forage quality and biomass properties for processing to fuels and bioproducts. However, modifying lignin content and/or composition in transgenic plants through down-regulation of lignin biosynthetic enzymes can induce expression of defense response genes in the absence of biotic or abiotic stress. lines with altered lignin through down-regulation of hydroxycinnamoyl CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT) or loss of function of cinnamoyl CoA reductase 1 (CCR1) express a suite of pathogenesis-related (PR) protein genes. The plants also exhibit extensive cell wall remodeling associated with induction of multiple cell wall-degrading enzymes, a process which renders the corresponding biomass a substrate for growth of the cellulolytic thermophile lacking a functional pectinase gene cluster. The cell wall remodeling also results in the release of size- and charge-heterogeneous pectic oligosaccharide elicitors of gene expression. Genetic analysis shows that both gene expression and release of elicitors are the result of ectopic expression in xylem of the gene ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE 1 (ADPG1), which is normally expressed during anther and silique dehiscence. These data highlight the importance of pectin in cell wall integrity and the value of lignin modification as a tool to interrogate the informational content of plant cell walls.
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http://dx.doi.org/10.1073/pnas.1914422117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022211PMC
February 2020

Multifeature analyses of vascular cambial cells reveal longevity mechanisms in old trees.

Proc Natl Acad Sci U S A 2020 01 13;117(4):2201-2210. Epub 2020 Jan 13.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, 100083 Beijing, China;

Aging is a universal property of multicellular organisms. Although some tree species can live for centuries or millennia, the molecular and metabolic mechanisms underlying their longevity are unclear. To address this, we investigated age-related changes in the vascular cambium from 15- to 667-y-old trees. The ring width decreased sharply during the first 100 to 200 y, with only a slight change after 200 y of age, accompanied by decreasing numbers of cambial cell layers. In contrast, average basal area increment (BAI) continuously increased with aging, showing that the lateral meristem can retain indeterminacy in old trees. The indole-3-acetic acid (IAA) concentration in cambial cells decreased with age, whereas the content of abscisic acid (ABA) increased significantly. In addition, cell division-, cell expansion-, and differentiation-related genes exhibited significantly lower expression in old trees, especially miR166 and HD-ZIP III interaction networks involved in cambial activity. Disease resistance-associated genes retained high expression in old trees, along with genes associated with synthesis of preformed protective secondary metabolites. Comprehensive evaluation of the expression of genes related to autophagy, senescence, and age-related miRNAs, together with analysis of leaf photosynthetic efficiencies and seed germination rates, demonstrated that the old trees are still in a healthy, mature state, and senescence is not manifested at the whole-plant level. Taken together, our results reveal that long-lived trees have evolved compensatory mechanisms to maintain a balance between growth and aging processes. This involves continued cambial divisions, high expression of resistance-associated genes, and continued synthetic capacity of preformed protective secondary metabolites.
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http://dx.doi.org/10.1073/pnas.1916548117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995005PMC
January 2020

Monosodium luminol reinstates redox homeostasis, improves cognition, mood and neurogenesis, and alleviates neuro- and systemic inflammation in a model of Gulf War Illness.

Redox Biol 2020 01 18;28:101389. Epub 2019 Nov 18.

Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, TX, USA.

Enduring brain dysfunction is amid the highly manifested symptoms in veterans with Gulf War Illness (GWI). Animal studies have established that lasting brain dysfunction in GWI is concomitant with augmented oxidative stress, inflammation, and declined neurogenesis in the brain, and systemic inflammation. We hypothesize that drugs capable of restoring redox homeostasis in GWI will improve cognitive and mood function with modulation of neuroinflammation and neurogenesis. We examined the efficacy of monosodium luminol-GVT (MSL), a drug that promotes redox homeostasis, for improving cognitive and mood function in GWI rats. Young rats were exposed to GWI-related chemicals and moderate restraint stress for four weeks. Four months later, GWI rats received different doses of MSL or vehicle for eight weeks. Behavioral analyses in the last three weeks of treatment revealed that GWI rats receiving higher doses of MSL displayed better cognitive and mood function associated with reinstatement of redox homeostasis. Such restoration was evident from the normalized expression of multiple genes encoding proteins involved in combating oxidative stress in the brain and the return of several oxidative stress markers to control levels in the brain and the circulating blood. Sustained redox homeostasis by MSL also resulted in antiinflammatory and pro-neurogenic effects, which were apparent from reduced densities of hypertrophied astrocytes and activated microglia, and increased neurogenesis with augmented neural stem cell proliferation. Moreover, MSL treatment normalized the concentration of multiple proinflammatory markers in the circulating blood. Thus, MSL treatment reinstated redox homeostasis in an animal model of GWI, which resulted in alleviation of both brain and systemic inflammation, improved neurogenesis, and better cognitive and mood function.
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http://dx.doi.org/10.1016/j.redox.2019.101389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888767PMC
January 2020

Finding New Cell Wall Regulatory Genes in Using Multiple Lines of Evidence.

Front Plant Sci 2019 8;10:1249. Epub 2019 Oct 8.

Biosciences Division, and The Center for Bioenergy Innovation, Oak Ridge National Laboratory, Oak Ridge, TN, United States.

Understanding the regulatory network controlling cell wall biosynthesis is of great interest in , both because of its status as a model woody perennial and its importance for lignocellulosic products. We searched for genes with putatively unknown roles in regulating cell wall biosynthesis using an extended network-based Lines of Evidence (LOE) pipeline to combine multiple omics data sets in , including gene coexpression, gene comethylation, population level pairwise SNP correlations, and two distinct SNP-metabolite Genome Wide Association Study (GWAS) layers. By incorporating validation, ranking, and filtering approaches we produced a list of nine high priority gene candidates for involvement in the regulation of cell wall biosynthesis. We subsequently performed a detailed investigation of candidate gene GROWTH-REGULATING FACTOR 9 (). To investigate the role of in regulating cell wall biosynthesis, we assessed the genome-wide connections of and a paralog across data layers with functional enrichment analyses, predictive transcription factor binding site analysis, and an independent comparison to eQTN data. Our findings indicate that PtGRF9 likely affects the cell wall by directly repressing genes involved in cell wall biosynthesis, such as and , and indirectly by regulating homeobox genes. Furthermore, evidence suggests that paralogs may act as transcriptional co-regulators that direct the global energy usage of the plant. Using our extended pipeline, we show multiple lines of evidence implicating the involvement of these genes in cell wall regulatory functions and demonstrate the value of this method for prioritizing candidate genes for experimental validation.
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http://dx.doi.org/10.3389/fpls.2019.01249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791931PMC
October 2019

Co-expression networks for plant biology: why and how.

Acta Biochim Biophys Sin (Shanghai) 2019 Sep;51(10):981-988

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA.

Co-expression network analysis is one of the most powerful approaches for interpretation of large transcriptomic datasets. It enables characterization of modules of co-expressed genes that may share biological functional linkages. Such networks provide an initial way to explore functional associations from gene expression profiling and can be applied to various aspects of plant biology. This review presents the applications of co-expression network analysis in plant biology and addresses optimized strategies from the recent literature for performing co-expression analysis on plant biological systems. Additionally, we describe the combined interpretation of co-expression analysis with other genomic data to enhance the generation of biologically relevant information.
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http://dx.doi.org/10.1093/abbs/gmz080DOI Listing
September 2019

Ectopic Defense Gene Expression Is Associated with Growth Defects in Lignin Pathway Mutants.

Plant Physiol 2019 09 9;181(1):63-84. Epub 2019 Jul 9.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, Texas 76201

Lignin provides essential mechanical support for plant cell walls but decreases the digestibility of forage crops and increases the recalcitrance of biofuel crops. Attempts to modify lignin content and/or composition by genetic modification often result in negative growth effects. Although several studies have attempted to address the basis for such effects in individual transgenic lines, no common mechanism linking lignin modification with perturbations in plant growth and development has yet been identified. To address whether a common mechanism exists, we have analyzed transposon insertion mutants resulting in independent loss of function of five enzymes of the monolignol pathway, as well as one double mutant, in the model legume These plants exhibit growth phenotypes from essentially wild type to severely retarded. Extensive phenotypic, transcriptomic, and metabolomics analyses, including structural characterization of differentially expressed compounds, revealed diverse phenotypic consequences of lignin pathway perturbation that were perceived early in plant development but were not predicted by lignin content or composition alone. Notable phenotypes among the mutants with severe growth impairment were increased trichome numbers, accumulation of a variety of triterpene saponins, and extensive but differential ectopic expression of defense response genes. No currently proposed model explains the observed phenotypes across all lines. We propose that reallocation of resources into defense pathways is linked to the severity of the final growth phenotype in monolignol pathway mutants of , although it remains unclear whether this is a cause or an effect of the growth impairment.
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http://dx.doi.org/10.1104/pp.19.00533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716239PMC
September 2019

4-Coumarate 3-hydroxylase in the lignin biosynthesis pathway is a cytosolic ascorbate peroxidase.

Nat Commun 2019 04 30;10(1):1994. Epub 2019 Apr 30.

BioDiscovery Institute, University of North Texas, Denton, TX, 76203, United States.

Lignin biosynthesis is evolutionarily conserved among higher plants and features a critical 3-hydroxylation reaction involving phenolic esters. However, increasing evidence questions the involvement of a single pathway to lignin formation in vascular plants. Here we describe an enzyme catalyzing the direct 3-hydroxylation of 4-coumarate to caffeate in lignin biosynthesis as a bifunctional peroxidase that oxidizes both ascorbate and 4-coumarate at comparable rates. A combination of biochemical and genetic evidence in the model plants Brachypodium distachyon and Arabidopsis thaliana supports a role for this coumarate 3-hydroxylase (C3H) in the early steps of lignin biosynthesis. The subsequent efficient O-methylation of caffeate to ferulate in grasses is substantiated by in vivo biochemical assays. Our results identify C3H as the only non-membrane bound hydroxylase in the lignin pathway and revise the currently accepted models of lignin biosynthesis, suggesting new gene targets to improve forage and bioenergy crops.
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http://dx.doi.org/10.1038/s41467-019-10082-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491607PMC
April 2019

Enzymatic basis for C-lignin monomer biosynthesis in the seed coat of Cleome hassleriana.

Plant J 2019 08 17;99(3):506-520. Epub 2019 May 17.

BioDiscovery Institute, University of North Texas, Denton, TX, USA.

C-lignin is a linear polymer of caffeyl alcohol, found in the seed coats of several exotic plant species, with promising properties for generation of carbon fibers and high value chemicals. In the ornamental plant Cleome hassleriana, guaiacyl (G) lignin is deposited in the seed coat for the first 6-12 days after pollination, after which G-lignin deposition ceases and C-lignin accumulates, providing an excellent model system to study C-lignin biosynthesis. We performed RNA sequencing of seed coats harvested at 2-day intervals throughout development. Bioinformatic analysis identified a complete set of lignin biosynthesis genes for Cleome. Transcript analysis coupled with kinetic analysis of recombinant enzymes in Escherichia coli revealed that the switch to C-lignin formation was accompanied by down-regulation of transcripts encoding functional caffeoyl CoA- and caffeic acid 3-O-methyltransferases (CCoAOMT and COMT) and a form of cinnamyl alcohol dehydrogenase (ChCAD4) with preference for coniferaldehyde as substrate, and up-regulation of a form of CAD (ChCAD5) with preference for caffealdehyde. Based on these analyses, blockage of lignin monomer methylation by down-regulation of both O-methyltransferases (OMTs) and methionine synthase (for provision of C1 units) appears to be the major factor in diversion of flux to C-lignin in the Cleome seed coat, although the change in CAD specificity also contributes based on the reduction of C-lignin levels in transgenic Cleome with down-regulation of ChCAD5. Structure modeling and mutational analysis identified amino acid residues important for the preference of ChCAD5 for caffealdehyde.
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http://dx.doi.org/10.1111/tpj.14340DOI Listing
August 2019

Corrigendum: The Differences between NAD-ME and NADP-ME Subtypes of C Photosynthesis: More than Decarboxylating Enzymes.

Front Plant Sci 2019;10:247. Epub 2019 Mar 8.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, TX, United States.

[This corrects the article DOI: 10.3389/fpls.2016.01525.].
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http://dx.doi.org/10.3389/fpls.2019.00247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418413PMC
March 2019

Proanthocyanidin subunit composition determined by functionally diverged dioxygenases.

Nat Plants 2018 12 26;4(12):1034-1043. Epub 2018 Nov 26.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, TX, USA.

Proanthocyanidins (PAs) are primarily composed of the flavan-3-ol subunits (-)-epicatechin and/or (+)-catechin, but the basis for their different starter and extension unit compositions remains unclear. Genetic and biochemical analyses show that, in the model legume Medicago truncatula, two 2-oxoglutarate-dependent dioxygenases, anthocyanidin synthase (ANS) and its homologue leucoanthocyanidin dioxygenase (LDOX), are involved in parallel pathways to generate, respectively, the (-)-epicatechin extension and starter units of PAs, with (+) catechin being an intermediate in the formation of the (-)-epicatechin starter unit. The presence/absence of the LDOX pathway accounts for natural differences in PA compositions across species, and engineering loss of function of ANS or LDOX provides a means to obtain PAs with different compositions and degrees of polymerization for use in food and feed.
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http://dx.doi.org/10.1038/s41477-018-0292-9DOI Listing
December 2018

Effect of Acyl Activating Enzyme (AAE) 3 on the growth and development of Medicago truncatula.

Biochem Biophys Res Commun 2018 10 20;505(1):255-260. Epub 2018 Sep 20.

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030-2600, USA. Electronic address:

The Acyl-Activating Enzyme (AAE) 3 gene encodes an oxalyl-CoA synthetase that catalyzes the conversion of oxalate to oxalyl-CoA in a CoA and ATP-dependent manner. Although the biochemical activity of AAE3 has been established, its biological role in plant growth and development remains unclear. To advance our understanding of the role of AAE3 in plant growth and development, we report here the characterization of two Medicago truncatula AAE3 (Mtaae3) mutants. Characterization of a Mtaae3 RNAi mutant revealed an accumulation of calcium oxalate crystals and increased seed permeability. These phenotypes were also exhibited in the Arabidopsis aae3 (Ataae3) mutants. Unlike the Ataae3 mutants, the Mtaae3 RNAi mutant did not show a reduction in vegetative growth, decreased seed germination, or increased seed calcium concentration. In an effort to clarify these phenotypic differences, a Mtaae3 Tnt1 mutant was identified and characterized. This Mtaae3 Tnt1 mutant displayed reduced vegetative growth, decreased seed germination, and increased seed calcium concentration as well as an accumulation of calcium oxalate crystals and increased seed permeability as found in Ataae3. Overall, the results presented here show the importance of AAE3 in the growth and development of plants. In addition, this study highlights the ability to separate specific growth and development phenotypes based on the level of AAE3 gene expression.
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http://dx.doi.org/10.1016/j.bbrc.2018.09.104DOI Listing
October 2018

Gene regulatory networks for lignin biosynthesis in switchgrass (Panicum virgatum).

Plant Biotechnol J 2019 03 17;17(3):580-593. Epub 2018 Sep 17.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, TX, USA.

Cell wall recalcitrance is the major challenge to improving saccharification efficiency in converting lignocellulose into biofuels. However, information regarding the transcriptional regulation of secondary cell wall biogenesis remains poor in switchgrass (Panicum virgatum), which has been selected as a biofuel crop in the United States. In this study, we present a combination of computational and experimental approaches to develop gene regulatory networks for lignin formation in switchgrass. To screen transcription factors (TFs) involved in lignin biosynthesis, we developed a modified method to perform co-expression network analysis using 14 lignin biosynthesis genes as bait (target) genes. The switchgrass lignin co-expression network was further extended by adding 14 TFs identified in this study, and seven TFs identified in previous studies, as bait genes. Six TFs (PvMYB58/63, PvMYB42/85, PvMYB4, PvWRKY12, PvSND2 and PvSWN2) were targeted to generate overexpressing and/or down-regulated transgenic switchgrass lines. The alteration of lignin content, cell wall composition and/or plant growth in the transgenic plants supported the role of the TFs in controlling secondary wall formation. RNA-seq analysis of four of the transgenic switchgrass lines revealed downstream target genes of the secondary wall-related TFs and crosstalk with other biological pathways. In vitro transactivation assays further confirmed the regulation of specific lignin pathway genes by four of the TFs. Our meta-analysis provides a hierarchical network of TFs and their potential target genes for future manipulation of secondary cell wall formation for lignin modification in switchgrass.
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http://dx.doi.org/10.1111/pbi.13000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381781PMC
March 2019

Elicitors and defense gene induction in plants with altered lignin compositions.

New Phytol 2018 09 27;219(4):1235-1251. Epub 2018 Jun 27.

BioDiscovery Institute and Department of Biological Sciences, BioDiscovery Institute, University of North Texas, Denton, TX, 76201, USA.

A reduction in the lignin content in transgenic plants induces the ectopic expression of defense genes, but the importance of altered lignin composition in such phenomena remains unclear. Two Arabidopsis lines with similar lignin contents, but strikingly different lignin compositions, exhibited different quantitative and qualitative transcriptional responses. Plants with lignin composed primarily of guaiacyl units overexpressed genes responsive to oomycete and bacterial pathogen attack, whereas plants with lignin composed primarily of syringyl units expressed a far greater number of defense genes, including some associated with cis-jasmone-mediated responses to aphids; these plants exhibited altered responsiveness to bacterial and aphid inoculation. Several of the defense genes were differentially induced by water-soluble extracts from cell walls of plants of the two lines. Glycome profiling, fractionation and enzymatic digestion studies indicated that the different lignin compositions led to differential extractability of a range of heterogeneous oligosaccharide epitopes, with elicitor activity originating from different cell wall polymers. Alteration of lignin composition affects interactions with plant cell wall matrix polysaccharides to alter the sequestration of multiple latent defense signal molecules with an impact on biotic stress responses.
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http://dx.doi.org/10.1111/nph.15258DOI Listing
September 2018

Current Models for Transcriptional Regulation of Secondary Cell Wall Biosynthesis in Grasses.

Front Plant Sci 2018 4;9:399. Epub 2018 Apr 4.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, TX, United States.

Secondary cell walls mediate many crucial biological processes in plants including mechanical support, water and nutrient transport and stress management. They also provide an abundant resource of renewable feed, fiber, and fuel. The grass family contains the most important food, forage, and biofuel crops. Understanding the regulatory mechanism of secondary wall formation in grasses is necessary for exploiting these plants for agriculture and industry. Previous research has established a detailed model of the secondary wall regulatory network in the dicot model species . Grasses, branching off from the dicot ancestor 140-150 million years ago, display distinct cell wall morphology and composition, suggesting potential for a different secondary wall regulation program from that established for dicots. Recently, combined application of molecular, genetic and bioinformatics approaches have revealed more transcription factors involved in secondary cell wall biosynthesis in grasses. Compared with the dicots, grasses exhibit a relatively conserved but nevertheless divergent transcriptional regulatory program to activate their secondary cell wall development and to coordinate secondary wall biosynthesis with other physiological processes.
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http://dx.doi.org/10.3389/fpls.2018.00399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893761PMC
April 2018

Dynamic changes in transcriptome and cell wall composition underlying brassinosteroid-mediated lignification of switchgrass suspension cells.

Biotechnol Biofuels 2017 30;10:266. Epub 2017 Nov 30.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, Denton, TX USA.

Background: Plant cell walls contribute the majority of plant biomass that can be used to produce transportation fuels. However, the complexity and variability in composition and structure of cell walls, particularly the presence of lignin, negatively impacts their deconstruction for bioenergy. Metabolic and genetic changes associated with secondary wall development in the biofuel crop switchgrass () have yet to be reported.

Results: Our previous studies have established a cell suspension system for switchgrass, in which cell wall lignification can be induced by application of brassinolide (BL). We have now collected cell wall composition and microarray-based transcriptome profiles for BL-induced and non-induced suspension cultures to provide an overview of the dynamic changes in transcriptional reprogramming during BL-induced cell wall modification. From this analysis, we have identified changes in candidate genes involved in cell wall precursor synthesis, cellulose, hemicellulose, and pectin formation and ester-linkage generation. We have also identified a large number of transcription factors with expression correlated with lignin biosynthesis genes, among which are candidates for control of syringyl (S) lignin accumulation.

Conclusion: Together, this work provides an overview of the dynamic compositional changes during brassinosteroid-induced cell wall remodeling, and identifies candidate genes for future plant genetic engineering to overcome cell wall recalcitrance.
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http://dx.doi.org/10.1186/s13068-017-0954-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707915PMC
November 2017

An Improved Silencing Vector: Greater Insert Stability and More Extensive VIGS.

Plant Physiol 2018 01 10;176(1):496-510. Epub 2017 Nov 10.

Noble Research Institute, LLC, Ardmore, Oklahoma 73401

Virus-induced gene silencing (VIGS) is used extensively for gene function studies in plants. VIGS is inexpensive and rapid compared with silencing conducted through stable transformation, but many virus-silencing vectors, especially in grasses, induce only transient silencing phenotypes. A major reason for transient phenotypes is the instability of the foreign gene fragment (insert) in the vector during VIGS. Here, we report the development of a (BMV)-based vector that better maintains inserts through modification of the original BMV vector RNA sequence. Modification of the BMV RNA3 sequence yielded a vector, BMVCP5, that better maintained and () inserts in and maize (). Longer maintenance of inserts was correlated with greater target gene silencing and more extensive visible silencing phenotypes displaying greater tissue penetration and involving more leaves. The modified vector accumulated similarly to the original vector in after agroinfiltration, thus maintaining a high titer of virus in this intermediate host used to produce virus inoculum for grass hosts. For , silencing one family member led to a large increase in the expression of another family member, an increase likely related to the target gene knockdown and not a general effect of virus infection. The cause of the increased insert stability in the modified vector is discussed in relationship to its recombination and accumulation potential. The modified vector will improve functional genomic studies in grasses, and the conceptual methods used to improve the vector may be applied to other VIGS vectors.
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http://dx.doi.org/10.1104/pp.17.00905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761774PMC
January 2018

Brassinosteroid Mediated Cell Wall Remodeling in Grasses under Abiotic Stress.

Front Plant Sci 2017 17;8:806. Epub 2017 May 17.

BioDiscovery Institute and Department of Biological Sciences, University of North Texas, DentonTX, United States.

Unlike animals, plants, being sessile, cannot escape from exposure to severe abiotic stresses such as extreme temperature and water deficit. The dynamic structure of plant cell wall enables them to undergo compensatory changes, as well as maintain physical strength, with changing environments. Plant hormones known as brassinosteroids (BRs) play a key role in determining cell wall expansion during stress responses. Cell wall deposition differs between grasses (Poaceae) and dicots. Grass species include many important food, fiber, and biofuel crops. In this article, we focus on recent advances in BR-regulated cell wall biosynthesis and remodeling in response to stresses, comparing our understanding of the mechanisms in grass species with those in the more studied dicots. A more comprehensive understanding of BR-mediated changes in cell wall integrity in grass species will benefit the development of genetic tools to improve crop productivity, fiber quality and plant biomass recalcitrance.
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http://dx.doi.org/10.3389/fpls.2017.00806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434148PMC
May 2017

A re-evaluation of the final step of vanillin biosynthesis in the orchid Vanilla planifolia.

Phytochemistry 2017 Jul 12;139:33-46. Epub 2017 Apr 12.

BioDiscovery Institute, University of North Texas, Denton, TX 76203, USA; Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA. Electronic address:

A recent publication describes an enzyme from the vanilla orchid Vanilla planifolia with the ability to convert ferulic acid directly to vanillin. The authors propose that this represents the final step in the biosynthesis of vanillin, which is then converted to its storage form, glucovanillin, by glycosylation. The existence of such a "vanillin synthase" could enable biotechnological production of vanillin from ferulic acid using a "natural" vanilla enzyme. The proposed vanillin synthase exhibits high identity to cysteine proteases, and is identical at the protein sequence level to a protein identified in 2003 as being associated with the conversion of 4-coumaric acid to 4-hydroxybenzaldehyde. We here demonstrate that the recombinant cysteine protease-like protein, whether expressed in an in vitro transcription-translation system, E. coli, yeast, or plants, is unable to convert ferulic acid to vanillin. Rather, the protein is a component of an enzyme complex that preferentially converts 4-coumaric acid to 4-hydroxybenzaldehyde, as demonstrated by the purification of this complex and peptide sequencing. Furthermore, RNA sequencing provides evidence that this protein is expressed in many tissues of V. planifolia irrespective of whether or not they produce vanillin. On the basis of our results, V. planifolia does not appear to contain a cysteine protease-like "vanillin synthase" that can, by itself, directly convert ferulic acid to vanillin. The pathway to vanillin in V. planifolia is yet to be conclusively determined.
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http://dx.doi.org/10.1016/j.phytochem.2017.04.003DOI Listing
July 2017

The Differences between NAD-ME and NADP-ME Subtypes of C Photosynthesis: More than Decarboxylating Enzymes.

Front Plant Sci 2016 13;7:1525. Epub 2016 Oct 13.

BioDiscovery Institute and Department of Biological Sciences, University of North TexasDenton, TX, USA; BioEnergy Science Center, US Department of EnergyOak Ridge, TN, USA.

As an adaptation to changing climatic conditions that caused high rates of photorespiration, C plants have evolved to display higher photosynthetic efficiency than C plants under elevated temperature, high light intensities, and drought. The C plants independently evolved more than 60 times in 19 families of angiosperms to establish similar but not uniform C mechanisms to concentrate CO around the carboxylating enzyme Rubisco (ribulose bisphosphate carboxylase oxygenase). C photosynthesis is divided into at least two basic biochemical subtypes based on the primary decarboxylating enzymes, NAD-dependent malic enzyme (NAD-ME) and NADP-dependent malic enzyme (NADP-ME). The multiple polygenetic origins of these subtypes raise questions about the association of C variation between biochemical subtypes and diverse lineages. This review addresses the differences in evolutionary scenario, leaf anatomy, and especially C metabolic flow, C transporters, and cell-specific function deduced from recently reported cell-specific transcriptomic, proteomic, and metabolic analyses of NAD-ME and NADP-ME subtypes. Current omic analysis has revealed the extent to which component abundances differ between the two biochemical subtypes, leading to a better understanding of C photosynthetic mechanisms in NAD-ME and NADP-ME subtypes.
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http://dx.doi.org/10.3389/fpls.2016.01525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061750PMC
October 2016

Comparative cell-specific transcriptomics reveals differentiation of C4 photosynthesis pathways in switchgrass and other C4 lineages.

J Exp Bot 2016 Mar 19;67(6):1649-62. Epub 2016 Feb 19.

Department of Biological Sciences, University of North Texas, 1155 Union Circle #305220, Denton, TX 76203, USA BioEnergy Science Center (BESC), US Department of Energy, Oak Ridge, TN 37831, USA

Almost all C4 plants require the co-ordination of the adjacent and fully differentiated cell types, mesophyll (M) and bundle sheath (BS). The C4 photosynthetic pathway operates through two distinct subtypes based on how malate is decarboxylated in BS cells; through NAD-malic enzyme (NAD-ME) or NADP-malic enzyme (NADP-ME). The diverse or unique cell-specific molecular features of M and BS cells from separate C4 subtypes of independent lineages remain to be determined. We here provide an M/BS cell type-specific transcriptome data set from the monocot NAD-ME subtype switchgrass (Panicum virgatum). A comparative transcriptomics approach was then applied to compare the M/BS mRNA profiles of switchgrass, monocot NADP-ME subtype C4 plants maize and Setaria viridis, and dicot NAD-ME subtype Cleome gynandra. We evaluated the convergence in the transcript abundance of core components in C4 photosynthesis and transcription factors to establish Kranz anatomy, as well as gene distribution of biological functions, in these four independent C4 lineages. We also estimated the divergence between NAD-ME and NADP-ME subtypes of C4 photosynthesis in the two cell types within C4 species, including differences in genes encoding decarboxylating enzymes, aminotransferases, and metabolite transporters, and differences in the cell-specific functional enrichment of RNA regulation and protein biogenesis/homeostasis. We suggest that C4 plants of independent lineages in both monocots and dicots underwent convergent evolution to establish C4 photosynthesis, while distinct C4 subtypes also underwent divergent processes for the optimization of M and BS cell co-ordination. The comprehensive data sets in our study provide a basis for further research on evolution of C4 species.
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http://dx.doi.org/10.1093/jxb/erv553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783356PMC
March 2016

Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation.

Sci Rep 2015 Dec 7;5:17807. Epub 2015 Dec 7.

Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.

Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy.
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http://dx.doi.org/10.1038/srep17807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671086PMC
December 2015
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