Subtilase-mediated biogenesis of the expanded family of SERINE RICH ENDOGENOUS PEPTIDES.

Plant signalling peptides are typically released from larger precursors by proteolytic cleavage to regulate plant growth, development and stress responses. Recent studies reported the characterization of a divergent family of Brassicaceae-specific peptides, SERINE RICH ENDOGENOUS PEPTIDES (SCOOPs), and their perception by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2). Here, we reveal that the SCOOP family is highly expanded, containing at least 50 members in the Columbia-0 reference Arabidopsis thaliana genome. Notably, perception of these peptides is strictly MIK2-dependent. How bioactive SCOOP peptides are produced, and to what extent their perception is responsible for the multiple physiological roles associated with MIK2 are currently unclear. Using N-terminomics, we validate the N-terminal cleavage site of representative PROSCOOPs. The cleavage sites are determined by conserved motifs upstream of the minimal SCOOP bioactive epitope. We identified subtilases necessary and sufficient to process PROSCOOP peptides at conserved cleavage motifs. Mutation of these subtilases, or their recognition motifs, suppressed PROSCOOP cleavage and associated overexpression phenotypes. Furthermore, we show that higher-order mutants of these subtilases show phenotypes reminiscent of mik2 null mutant plants, consistent with impaired PROSCOOP biogenesis, and demonstrating biological relevance of SCOOP perception by MIK2. Together, this work provides insights into the molecular mechanisms underlying the functions of the recently identified SCOOP peptides and their receptor MIK2.

The PROSCOOP10 Gene Encodes Two Extracellular Hydroxylated Peptides and Impacts Flowering Time in Arabidopsis.

The Arabidopsis PROSCOOP genes belong to a family predicted to encode secreted pro-peptides, which undergo maturation steps to produce peptides named SCOOP. Some of them are involved in defence signalling through their perception by a receptor complex including MIK2, BAK1 and BKK1. Here, we focused on the PROSCOOP10 gene, which is highly and constitutively expressed in aerial organs. The MS/MS analyses of leaf apoplastic fluids allowed the identification of two distinct peptides (named SCOOP10#1 and SCOOP10#2) covering two different regions of PROSCOOP10. They both possess the canonical S-X-S family motif and have hydroxylated prolines. This identification in apoplastic fluids confirms the biological reality of SCOOP peptides for the first time. NMR and molecular dynamics studies showed that the SCOOP10 peptides, although largely unstructured in solution, tend to assume a hairpin-like fold, exposing the two serine residues previously identified as essential for the peptide activity. Furthermore, PROSCOOP10 mutations led to an early-flowering phenotype and increased expression of the floral integrators SOC1 and LEAFY, consistent with the de-regulated transcription of PROSCOOP10 in several other mutants displaying early- or late-flowering phenotypes. These results suggest a role for PROSCOOP10 in flowering time, highlighting the functional diversity within the PROSCOOP family.

Seed Transmission of Pathogens: Non-Canonical Immune Response in Arabidopsis Germinating Seeds Compared to Early Seedlings against the Necrotrophic Fungus Alternaria brassicicola.

The transmission of seed-borne pathogens by the germinating seed is responsible for major crop diseases. The immune responses of the seed facing biotic invaders are poorly documented so far. The Arabidopsis thaliana/Alternaria brassicicola patho-system was used to describe at the transcription level the responses of germinating seeds and young seedling stages to infection by the necrotrophic fungus. RNA-seq analyses of healthy versus inoculated seeds at 3 days after sowing (DAS), stage of radicle emergence, and at 6 and 10 DAS, two stages of seedling establishment, identified thousands of differentially expressed genes by Alternaria infection. Response to hypoxia, ethylene and indole pathways were found to be induced by Alternaria in the germinating seeds. However, surprisingly, the defense responses, namely the salicylic acid (SA) pathway, the response to reactive oxygen species (ROS), the endoplasmic reticulum-associated protein degradation (ERAD) and programmed cell death, were found to be strongly induced only during the latter post-germination stages. We propose that this non-canonical immune response in early germinating seeds compared to early seedling establishment was potentially due to the seed-to-seedling transition phase. Phenotypic analyses of about 14 mutants altered in the main defense pathways illustrated these specific defense responses. The unexpected germination deficiency and insensitivity to Alternaria in the glucosinolate deficient mutants allow hypothesis of a trade-off between seed germination, necrosis induction and Alternaria transmission to the seedling. The imbalance of the SA and jasmonic acid (JA) pathways to the detriment of the JA also illustrated a non-canonical immune response at the first stages of the seedling.

The peptide SCOOP12 acts on reactive oxygen species homeostasis to modulate cell division and elongation in Arabidopsis primary root.

Small secreted peptides have been described as key contributors to complex signalling networks that control plant development and stress responses. The Brassicaceae-specific PROSCOOP family encodes precursors of Serine riCh endOgenOus Peptides (SCOOPs). In Arabidopsis SCOOP12 has been shown to promote the defence response against pathogens and to be involved in root development. Here, we explore its role as a moderator of Arabidopsis primary root development. We show that the PROSCOOP12 null mutation leads to longer primary roots through the development of longer differentiated cells while PROSCOOP12 overexpression induces dramatic plant growth impairments. In comparison, the exogenous application of synthetic SCOOP12 peptide shortens roots through meristem size and cell length reductions. Moreover, superoxide anion (O2·-) and hydrogen peroxide (H2O2) production in root tips vary according to SCOOP12 abundance. By using reactive oxygen species scavengers that suppress the proscoop12 phenotype, we showed that root growth regulation by SCOOP12 is associated with reactive oxygen species metabolism. Furthermore, our results suggest that peroxidases act as potential SCOOP12 downstream targets to regulate H2O2 production, which in turn triggers cell wall modifications in root. Finally, a massive transcriptional reprogramming, including the induction of genes from numerous other pathways, including ethylene, salicylic acid, and glucosinolates biosynthesis, was observed, emphasizing its dual role in defence and development.

The MIK2/SCOOP Signaling System Contributes to Arabidopsis Resistance Against Herbivory by Modulating Jasmonate and Indole Glucosinolate Biosynthesis.

Initiation of plant immune signaling requires recognition of conserved molecular patterns from microbes and herbivores by plasma membrane-localized pattern recognition receptors. Additionally, plants produce and secrete numerous small peptide hormones, termed phytocytokines, which act as secondary danger signals to modulate immunity. In Arabidopsis, the Brassicae-specific SERINE RICH ENDOGENOUS PEPTIDE (SCOOP) family consists of 14 members that are perceived by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR LIKE KINASE 2 (MIK2). Recognition of SCOOP peptides elicits generic early signaling responses but knowledge on how and if SCOOPs modulate specific downstream immune defenses is limited. We report here that depletion of MIK2 or the single PROSCOOP12 precursor results in decreased Arabidopsis resistance against the generalist herbivore Spodoptera littoralis but not the specialist Pieris brassicae. Increased performance of S. littoralis on mik2-1 and proscoop12 is accompanied by a diminished accumulation of jasmonic acid, jasmonate-isoleucine and indolic glucosinolates. Additionally, we show transcriptional activation of the PROSCOOP gene family in response to insect herbivory. Our data therefore indicate that perception of endogenous SCOOP peptides by MIK2 modulates the jasmonate pathway and thereby contributes to enhanced defense against a generalist herbivore.

Technical benefit on apple fruit of controlled atmosphere influenced by 1-MCP at molecular levels.

The apple is a highly perishable fruit after harvesting and, therefore, several storage technologies have been studied to provide the consumer market with a quality product with a longer shelf life. However, little is known about the apple genome that is submitted to the storage, and even less with the application of ripening inhibitors. Due to these factors, this study sought to elucidate the transcriptional profile of apple cultivate Gala stored in a controlled atmosphere (AC) treated and not treated with 1-methyl cyclopropene (1-MCP). Through the genetic mapping of the apple, applying the microarray technique, it was possible to verify the action of treatments on transcripts related to photosynthesis, carbohydrate metabolism, response to hormonal stimuli, nucleic acid metabolism, reduction of oxidation, regulation of transcription and metabolism of cell wall and lipids. The results showed that the transcriptional profile in the entire genome of the fruit showed significant differences in the relative expression of the gene, this in response to CA in the presence and absence of 1-MCP. It should be noted that the transcription genes involved in the anabolic pathway were only maintained after six months in fruits treated with 1-MCP. The data in this work suggests that the apple in the absence of 1-MCP begins to prepare its metabolism to mature, even during the storage period in AC. Meanwhile, in the presence of the inhibitor, the transcriptional profile of the fruit is similar to that at the time of harvest. It was also found that a set of genes that code for ethylene receptors, auxin homeostasis, MADS Box, and NAC transcription factors may be involved in the regulation of post-harvest ripening after storage and in the absence of 1-MCP.

Pre-harvest climate and post-harvest acclimation to cold prevent from superficial scald development in Granny Smith apples.

Superficial scald is one of the most serious postharvest physiological disorders that can affect apples after a prolonged cold storage period. This study investigated the impact of pre- and post-harvest climatic variations on superficial scald in a susceptible apple cultivar. Fruit batches with contrasting phenotypes for superficial scald incidence were identified among several years of "Granny Smith" fruit production. The "low scald" year pre-harvest climate was characterised by a warm period followed by a sudden decrease in temperature, playing the part of an in vivo acclimation to cold storage. This was associated with many abiotic stress responsive genes which were induced in fruit peel. In particular 48 Heat Shock Proteins (HSPs) and 5 Heat Shock transcription Factors (HSFs) were strongly induced at harvest when scald incidence was low. For "high scald" year, a post-harvest acclimation of 1 week was efficient in reducing scald incidence. Expression profiles of stress related genes were affected by the acclimation treatment and indicate fruit physiological adaptations to cold storage. The identified stress-responsive genes, and in particular HSPs, could be useful indicators of the fruit physiological status to predict the risk of scald occurrence as early as harvest.

Responses of the Necrotrophic Fungus Alternaria brassisicola to the Indolic Phytoalexin Brassinin.

Alternaria brassicicola causes black spot disease in Brassicaceae. During host infection, this necrotrophic fungus is exposed to various antimicrobial compounds, such as the phytoalexin brassinin which is produced by many cultivated Brassica species. To investigate the cellular mechanisms by which this compound causes toxicity and the corresponding fungal adaptive strategies, we first analyzed fungal transcriptional responses to short-term exposure to brassinin and then used additional functional approaches. This study supports the hypothesis that indolic phytoalexin primarily targets mitochondrial functions in fungal cells. Indeed, we notably observed that phytoalexin treatment of A. brassicicola disrupted the mitochondrial membrane potential and resulted in a significant and rapid decrease in the oxygen consumption rates. Secondary effects, such as Reactive oxygen species production, changes in lipid and endoplasmic reticulum homeostasis were then found to be induced. Consequently, the fungus has to adapt its metabolism to protect itself against the toxic effects of these molecules, especially via the activation of high osmolarity glycerol and cell wall integrity signaling pathways and by induction of the unfolded protein response.

Responses to Hydric Stress in the Seed-Borne Necrotrophic Fungus Alternaria brassicicola.

Alternaria brassicicola is a necrotrophic fungus causing black spot disease and is an economically important seed-borne pathogen of cultivated brassicas. Seed transmission is a crucial component of its parasitic cycle as it promotes long-term survival and dispersal. Recent studies, conducted with the Arabidopsis thaliana/A. brassicicola pathosystem, showed that the level of susceptibility of the fungus to water stress strongly influenced its seed transmission ability. In this study, we gained further insights into the mechanisms involved in the seed infection process by analyzing the transcriptomic and metabolomic responses of germinated spores of A. brassicicola exposed to water stress. Then, the repertoire of putative hydrophilins, a group of proteins that are assumed to be involved in cellular dehydration tolerance, was established in A. brassicicola based on the expression data and additional structural and biochemical criteria. Phenotyping of single deletion mutants deficient for fungal hydrophilin-like proteins showed that they were affected in their transmission to A. thaliana seeds, although their aggressiveness on host vegetative tissues remained intact.

The SCOOP12 peptide regulates defense response and root elongation in Arabidopsis thaliana.

Small secreted peptides are important players in plant development and stress response. Using a targeted in silico approach, we identified a family of 14 Arabidopsis genes encoding precursors of serine-rich endogenous peptides (PROSCOOP). Transcriptomic analyses revealed that one member of this family, PROSCOOP12, is involved in processes linked to biotic and oxidative stress as well as root growth. Plants defective in this gene were less susceptible to Erwinia amylovora infection and showed an enhanced root growth phenotype. In PROSCOOP12 we identified a conserved motif potentially coding for a small secreted peptide. Exogenous application of synthetic SCOOP12 peptide induces various defense responses in Arabidopsis. Our findings show that SCOOP12 has numerous properties of phytocytokines, activates the phospholipid signaling pathway, regulates reactive oxygen species response, and is perceived in a BAK1 co-receptor-dependent manner.

Large scale study of anti-sense regulation by differential network analysis.

BACKGROUND: Systems biology aims to analyse regulation mechanisms into the cell. By mapping interactions observed in different situations, differential network analysis has shown its power to reveal specific cellular responses or specific dysfunctional regulations. In this work, we propose to explore on a large scale the role of natural anti-sense transcription on gene regulation mechanisms, and we focus our study on apple (Malus domestica) in the context of fruit ripening in cold storage. RESULTS: We present a differential functional analysis of the sense and anti-sense transcriptomic data that reveals functional terms linked to the ripening process. To develop our differential network analysis, we introduce our inference method of an Extended Core Network; this method is inspired by C3NET, but extends the notion of significant interactions. By comparing two extended core networks, one inferred with sense data and the other one inferred with sense and anti-sense data, our differential analysis is first performed on a local view and reveals AS-impacted genes, genes that have important interactions impacted by anti-sense transcription. The motifs surrounding AS-impacted genes gather transcripts with functions mostly consistent with the biological context of the data used and the method allows us to identify new actors involved in ripening and cold acclimation pathways and to decipher their interactions. Then from a more global view, we compute minimal sub-networks that connect the AS-impacted genes using Steiner trees. Those Steiner trees allow us to study the rewiring of the AS-impacted genes in the network with anti-sense actors. CONCLUSION: Anti-sense transcription is usually ignored in transcriptomic studies. The large-scale differential analysis of apple data that we propose reveals that anti-sense regulation may have an important impact in several cellular stress response mechanisms. Our data mining process enables to highlight specific interactions that deserve further experimental investigations.

Screening of ordinary commercial varieties of apple fruits under different storage conditions for their potential vascular and metabolic protective properties.

Epidemiological studies reported that apple consumption is associated with a decrease of cardiovascular and metabolic dysfunction, probably due to the polyphenols and fibers present in this fruit. The storage conditions and genetic origin of apples have been reported to influence their content and, as a consequence, their pharmacological properties. The present study evaluated the influence of varieties and storage conditions of traditional and highly appreciated apples including Gala, Golden Delicious, Granny Smith and Pink Lady varieties after harvest and storage under classic cold conditions, under a controlled atmosphere, or under extreme ultra-low oxygen conditions. Thus, a multi-parametric screening on cell models associated with vascular and metabolic dysfunctions - such as endothelial and smooth muscle cells, hepatocytes, adipocytes and macrophages - in relation to the apple polyphenol content has been developed. This strategy demonstrated that, overall, peeled apple samples exhibited a vascular tropism and acted mainly on proliferation and oxidative stress in endothelial and smooth muscle cells. Apple extracts appeared to be less effective on adipocytes and macrophages, but they exhibited antioxidant properties in hepatocytes. Among the varieties, Gala and Golden Delicious were the most efficient against the processes involved in the development of atherosclerosis. Concerning storage conditions, most of the apple varieties were more efficient under harvest conditions, while they could not be discriminated under all other cold conditions and the concentration used, except for the Gala samples. Interestingly, pharmacological properties were associated with the polyphenol profiles of freeze dried apple flesh powder. The present report revealed the potential use of some apple extracts as effective food supplements or nutraceuticals for the prevention and/or management of cardiovascular and metabolic diseases.

Contrasting Transcriptional Programs Control Postharvest Development of Apples (Malus x domestica Borkh.) Submitted to Cold Storage and Ethylene Blockage.

Apple is commercially important worldwide. Favorable genomic contexts and postharvest technologies allow year-round availability. Although ripening is considered a unidirectional developmental process toward senescence, storage at low temperatures, alone or in combination with ethylene blockage, is effective in preserving apple properties. Quality traits and genome wide expression were integrated to investigate the mechanisms underlying postharvest changes. Development and conservation techniques were responsible for transcriptional reprogramming and distinct programs associated with quality traits. A large portion of the differentially regulated genes constitutes a program involved in ripening and senescence, whereas a smaller module consists of genes associated with reestablishment and maintenance of juvenile traits after harvest. Ethylene inhibition was associated with a reversal of ripening by transcriptional induction of anabolic pathways. Our results demonstrate that the blockage of ethylene perception and signaling leads to upregulation of genes in anabolic pathways. We also associated complex phenotypes to subsets of differentially regulated genes.

Cell wall dynamics during apple development and storage involves hemicellulose modifications and related expressed genes.

BACKGROUND: Fruit quality depends on a series of biochemical events that modify appearance, flavour and texture throughout fruit development and ripening. Cell wall polysaccharide remodelling largely contributes to the elaboration of fleshy fruit texture. Although several genes and enzymes involved in cell wall polysaccharide biosynthesis and modifications are known, their coordinated activity in these processes is yet to be discovered. RESULTS: Combined transcriptomic and biochemical analyses allowed the identification of putative enzymes and related annotated members of gene families involved in cell wall polysaccharide composition and structural changes during apple fruit growth and ripening. The early development genes were mainly related to cell wall biosynthesis and degradation with a particular target on hemicelluloses. Fine structural evolutions of galactoglucomannan were strongly correlated with mannan synthase, glucanase (GH9) and ß-galactosidase gene expression. In contrast, fewer genes related to pectin metabolism and cell expansion (expansin genes) were observed in ripening fruit combined with expected changes in cell wall polysaccharide composition. CONCLUSIONS: Hemicelluloses undergo major structural changes particularly during early fruit development. The high number of early expressed ß-galactosidase genes questions their function on galactosylated structures during fruit development and storage. Their activity and cell wall substrate remains to be identified. Moreover, new insights into the potential role of peroxidases and transporters, along with cell wall metabolism open the way to further studies on concomitant mechanisms involved in cell wall assembly/disassembly during fruit development and storage.

Correction: Misregulation of AUXIN RESPONSE FACTOR 8 Underlies the Developmental Abnormalities Caused by Three Distinct Viral Silencing Suppressors in Arabidopsis.

[This corrects the article DOI: 10.1371/journal.ppat.1002035.].

Transcriptome dynamics of a susceptible wheat upon Fusarium head blight reveals that molecular responses to Fusarium graminearum infection fit over the grain development processes.

In many plant/pathogen interactions, host susceptibility factors are key determinants of disease development promoting pathogen growth and spreading in plant tissues. In the Fusarium head blight (FHB) disease, the molecular basis of wheat susceptibility is still poorly understood while it could provide new insights into the understanding of the wheat/Fusarium graminearum (Fg) interaction and guide future breeding programs to produce cultivars with sustainable resistance. To identify the wheat grain candidate genes, a genome-wide gene expression profiling was performed in the French susceptible wheat cultivar, Recital. Gene-specific two-way ANOVA of about 40 K transcripts at five grain developmental stages identified 1309 differentially expressed genes. Out of these, 536 were impacted by the Fg effect alone. Most of these Fg-responsive genes belonged to biological and molecular functions related to biotic and abiotic stresses indicating the activation of common stress pathways during susceptibility response of wheat grain to FHB. This analysis revealed also 773 other genes displaying either specific Fg-responsive profiles along with grain development stages or synergistic adjustments with the grain development effect. These genes were involved in various molecular pathways including primary metabolism, cell death, and gene expression reprogramming. An increasingly complex host response was revealed, as was the impact of both Fg infection and grain ontogeny on the transcription of wheat genes. This analysis provides a wealth of candidate genes and pathways involved in susceptibility responses to FHB and depicts new clues to the understanding of the susceptibility determinism in plant/pathogen interactions.

Leaf-mining by Phyllonorycter blancardella reprograms the host-leaf transcriptome to modulate phytohormones associated with nutrient mobilization and plant defense.

Phytohormones have long been hypothesized to play a key role in the interactions between plant-manipulating organisms and their host-plants such as insect-plant interactions that lead to gall or 'green-islands' induction. However, mechanistic understanding of how phytohormones operate in these plant reconfigurations is lacking due to limited information on the molecular and biochemical phytohormonal modulation following attack by plant-manipulating insects. In an attempt to fill this gap, the present study provides an extensive characterization of how the leaf-miner Phyllonorycter blancardella modulates the major phytohormones and the transcriptional activity of plant cells in leaves of Malus domestica. We show here, that cytokinins strongly accumulate in mined tissues despite a weak expression of plant cytokinin-related genes. Leaf-mining is also associated with enhanced biosynthesis of jasmonic acid precursors but not the active form, a weak alteration of the salicylic acid pathway and a clear inhibition of the abscisic acid pathway. Our study consolidates previous results suggesting that insects may produce and deliver cytokinins to the plant as a strategy to manipulate the physiology of the leaf to create a favorable nutritional environment. We also demonstrate that leaf-mining by P. blancardella leads to a strong reprogramming of the plant phytohormonal balance associated with increased nutrient mobilization, inhibition of leaf senescence and mitigation of plant direct and indirect defense.

Transcription profiling of the chilling requirement for bud break in apples: a putative role for FLC-like genes.

Apple production depends on the fulfilment of a chilling requirement for bud dormancy release. Insufficient winter chilling results in irregular and suboptimal bud break in the spring, with negative impacts on apple yield. Trees from apple cultivars with contrasting chilling requirements for bud break were used to investigate the expression of the entire set of apple genes in response to chilling accumulation in the field and controlled conditions. Total RNA was analysed on the AryANE v.1.0 oligonucleotide microarray chip representing 57,000 apple genes. The data were tested for functional enrichment, and differential expression was confirmed by real-time PCR. The largest number of differentially expressed genes was found in samples treated with cold temperatures. Cold exposure mostly repressed expression of transcripts related to photosynthesis, and long-term cold exposure repressed flavonoid biosynthesis genes. Among the differentially expressed selected candidates, we identified genes whose annotations were related to the circadian clock, hormonal signalling, regulation of growth, and flower development. Two genes, annotated as FLOWERING LOCUS C-like and MADS AFFECTING FLOWERING, showed strong differential expression in several comparisons. One of these two genes was upregulated in most comparisons involving dormancy release, and this gene's chromosomal position co-localized with the confidence interval of a major quantitative trait locus for the timing of bud break. These results indicate that photosynthesis and auxin transport are major regulatory nodes of apple dormancy and unveil strong candidates for the control of bud dormancy.

GEM2Net: from gene expression modeling to -omics networks, a new CATdb module to investigate Arabidopsis thaliana genes involved in stress response.

CATdb (http://urgv.evry.inra.fr/CATdb) is a database providing a public access to a large collection of transcriptomic data, mainly for Arabidopsis but also for other plants. This resource has the rare advantage to contain several thousands of microarray experiments obtained with the same technical protocol and analyzed by the same statistical pipelines. In this paper, we present GEM2Net, a new module of CATdb that takes advantage of this homogeneous dataset to mine co-expression units and decipher Arabidopsis gene functions. GEM2Net explores 387 stress conditions organized into 18 biotic and abiotic stress categories. For each one, a model-based clustering is applied on expression differences to identify clusters of co-expressed genes. To characterize functions associated with these clusters, various resources are analyzed and integrated: Gene Ontology, subcellular localization of proteins, Hormone Families, Transcription Factor Families and a refined stress-related gene list associated to publications. Exploiting protein-protein interactions and transcription factors-targets interactions enables to display gene networks. GEM2Net presents the analysis of the 18 stress categories, in which 17,264 genes are involved and organized within 681 co-expression clusters. The meta-data analyses were stored and organized to compose a dynamic Web resource.

Progressive brain metabolic changes under deep brain stimulation of subthalamic nucleus in parkinsonian rats.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient neurosurgical treatment for advanced Parkinson's disease. Non-invasive metabolic neuroimaging during the course of DBS in animal models may contribute to our understanding of its action mechanisms. Here, DBS was adapted to in vivo proton magnetic resonance spectroscopy at 11.7 T in the rat to follow metabolic changes in main basal ganglia structures, the striatum, and the substantia nigra pars reticulata (SNr). Measurements were repeated OFF and ON acute and subchronic (7 days) STN-DBS in control and parkinsonian (6-hydroxydopamine lesion) conditions. Acute DBS reversed the increases in glutamate, glutamine, and GABA levels induced by the dopamine lesion in the striatum but not in the SNr. Subchronic DBS normalized GABA in both the striatum and SNr, and glutamate in the striatum. Taurine levels were markedly decreased under subchronic DBS in the striatum and SNr in both lesioned and unlesioned rats. Microdialysis in the striatum further showed that extracellular taurine was increased. These data reveal that STN-DBS has duration-dependent metabolic effects in the basal ganglia, consistent with development of adaptive mechanisms. In addition to counteracting defects induced by the dopamine lesion, prolonged DBS has proper effects independent of the pathological condition. Non-invasive metabolic neuroimaging might be useful to understand the physiological mechanisms of deep brain stimulation (DBS). Here, we demonstrate the feasibility of repeated high-field proton magnetic resonance spectroscopy of basal ganglia structures under subthalamic nucleus DBS in control and parkinsonian rats. Results show that DBS has both rapid and delayed effects either dependent or independent of disease state.