Repurposing Simvastatin in Parkinson's Disease Model: Protection Is throughout Modulation of the Neuro-Inflammatory Response in the Substantia nigra.

Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP+-induced damage compared to the MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson's disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.

Cardiorespiratory and Metabolic Responses to Loaded Half Squat Exercise Executed at an Intensity Corresponding to the Lactate Threshold.

This study was designed to identify the blood lactate threshold (LT2) for the half squat (HS) and to examine cardiorespiratory and metabolic variables during a HS test performed at a work intensity corresponding to the LT2. Twenty-four healthy men completed 3 test sessions. In the first, their one-repetition maximum (1RM) was determined for the HS. In the second session, a resistance HS incremental-load test was performed to determine LT2. Finally, in the third session, subjects performed a constant-load HS exercise at the load corresponding to the LT2 (21 sets of 15 repetitions with 1 min of rest between sets). In this last test, blood samples were collected for lactate determination before the test and 30 s after the end of set (S) 3, S6, S9, S12, S15, S18 and S21. During the test, heart rate (HR) was telemetrically monitored and oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), respiratory exchange ratio (RER), ventilatory equivalent for O2 (VE·VO2 (-1)) and ventilatory equivalent for CO2 (VE·VCO2 (-1)) were monitored using a breath-by-breath respiratory gas analyzer. The mean LT2 for the participants was 24.8 ± 4.8% 1RM. Blood lactate concentrations showed no significant differences between sets 3 and 21 of exercise (p = 1.000). HR failed to vary between S6 and S21 (p > 1.000). The respiratory variables VO2, VCO2, and VE·VCO2 (-1) stabilized from S3 to the end of the constant-load HS test (p = 0.471, p = 0.136, p = 1.000), while VE and VE·VO2 (-1) stabilized from S6 to S21. RER did not vary significantly across exercise sets (p = 0.103). The LT2 was readily identified in the incremental HS test. Cardiorespiratory and metabolic variables remained stable during this resistance exercise conducted at an exercise intensity corresponding to the LT2. These responses need to be confirmed for other resistance exercises and adaptations in these responses after a training program also need to be addressed. Key pointsIt can be identified lactate threshold at half-squat.Exercise intensity is predominantly aerobic.The duration of the half-squat can be maintained over time, ~30 min of discontinuous exercise (21 sets, 15 repetitions, 1 min rest).Lactate threshold intensity may be suitable for older adults, sedentary individuals, patients or subjects with a lower functional capacity and even for resistance sports athletes.

Effects of instability versus traditional resistance training on strength, power and velocity in untrained men.

The purpose of this study was compare the effects of a traditional and an instability resistance circuit training program on upper and lower limb strength, power, movement velocity and jumping ability. Thirty-six healthy untrained men were assigned to two experimental groups and a control group. Subjects in the experimental groups performed a resistance circuit training program consisting of traditional exercises (TRT, n = 10) or exercises executed in conditions of instability (using BOSU® and TRX®) (IRT, n = 12). Both programs involved three days per week of training for a total of seven weeks. The following variables were determined before and after training: maximal strength (1RM), average (AV) and peak velocity (PV), average (AP) and peak power (PP), all during bench press (BP) and back squat (BS) exercises, along with squat jump (SJ) height and counter movement jump (CMJ) height. All variables were found to significantly improve (p <0.05) in response to both training programs. Major improvements were observed in SJ height (IRT = 22.1%, TRT = 20.1%), CMJ height (IRT = 17.7%, TRT = 15.2%), 1RM in BS (IRT = 13.03%, TRT = 12.6%), 1RM in BP (IRT = 4.7%, TRT = 4.4%), AP in BS (IRT = 10.5%, TRT = 9.3%), AP in BP (IRT = 2.4%, TRT = 8.1%), PP in BS (IRT=19.42%, TRT = 22.3%), PP in BP (IRT = 7.6%, TRT = 11.5%), AV in BS (IRT = 10.5%, TRT = 9.4%), and PV in BS (IRT = 8.6%, TRT = 4.5%). Despite such improvements no significant differences were detected in the posttraining variables recorded for the two experimental groups. These data indicate that a circuit training program using two instability training devices is as effective in untrained men as a program executed under stable conditions for improving strength (1RM), power, movement velocity and jumping ability. Key PointsSimilar adaptations in terms of gains in strength, power, movement velocity and jumping ability were produced in response to both training programs.Both the stability and instability approaches seem suitable for healthy, physically-active individuals with or with limited experience in resistance training.RPE emerged as a useful tool to monitor exercise intensity during instability strength training.

Regulatory gene candidates and gene expression analysis of cold acclimation in winter and spring wheat.

Freezing tolerance in plants develops through acclimation to cold by growth at low, above-freezing temperatures. Wheat is one of the most freezing-tolerant plants among major crop species and the wide range of freezing tolerance among wheat cultivars makes it an excellent model for investigation of the genetic basis of cold tolerance. Large numbers of genes are known to have altered levels of expression during the period of cold acclimation and there is keen interest in deciphering the signaling and regulatory pathways that control the changes in gene expression associated with acquired freezing tolerance. A 5740 feature cDNA amplicon microarray that was enriched for signal transduction and regulatory genes was constructed to compare changes in gene expression in a highly cold-tolerant winter wheat cultivar CDC Clair and a less tolerant spring cultivar, Quantum. Changes in gene expression over a time course of 14 days detected over 450 genes that were regulated by cold treatment and were differentially regulated between spring and winter cultivars, of these 130 are signaling or regulatory gene candidates, including: transcription factors, protein kinases, ubiquitin ligases and GTP, RNA and calcium binding proteins. Dynamic changes in transcript levels were seen at all periods of cold acclimation in both cultivars. There was an initial burst of gene activity detectable during the first day of CA, during which 90% of all genes with increases in transcript levels became clearly detectable and early expression differential between the two cultivars became more disparate with each successive period of cold acclimation.

Wheat EST resources for functional genomics of abiotic stress.

BACKGROUND: Wheat is an excellent species to study freezing tolerance and other abiotic stresses. However, the sequence of the wheat genome has not been completely characterized due to its complexity and large size. To circumvent this obstacle and identify genes involved in cold acclimation and associated stresses, a large scale EST sequencing approach was undertaken by the Functional Genomics of Abiotic Stress (FGAS) project. RESULTS: We generated 73,521 quality-filtered ESTs from eleven cDNA libraries constructed from wheat plants exposed to various abiotic stresses and at different developmental stages. In addition, 196,041 ESTs for which tracefiles were available from the National Science Foundation wheat EST sequencing program and DuPont were also quality-filtered and used in the analysis. Clustering of the combined ESTs with d2_cluster and TGICL yielded a few large clusters containing several thousand ESTs that were refractory to routine clustering techniques. To resolve this problem, the sequence proximity and "bridges" were identified by an e-value distance graph to manually break clusters into smaller groups. Assembly of the resolved ESTs generated a 75,488 unique sequence set (31,580 contigs and 43,908 singletons/singlets). Digital expression analyses indicated that the FGAS dataset is enriched in stress-regulated genes compared to the other public datasets. Over 43% of the unique sequence set was annotated and classified into functional categories according to Gene Ontology. CONCLUSION: We have annotated 29,556 different sequences, an almost 5-fold increase in annotated sequences compared to the available wheat public databases. Digital expression analysis combined with gene annotation helped in the identification of several pathways associated with abiotic stress. The genomic resources and knowledge developed by this project will contribute to a better understanding of the different mechanisms that govern stress tolerance in wheat and other cereals.

Transcriptome comparison of winter and spring wheat responding to low temperature.

Freezing tolerance in plants is a complex trait that occurs in many plant species during growth at low, nonfreezing temperatures, a process known as cold acclimation. This process is regulated by a multigenic system expressing broad variation in the degree of freezing tolerance among wheat cultivars. Microarray analysis is a powerful and rapid approach to gene discovery. In species such as wheat, for which large scale mutant screening and transgenic studies are not currently practical, genotype comparison by this methodology represents an essential approach to identifying key genes in the acquisition of freezing tolerance. A microarray was constructed with PCR amplified cDNA inserts from 1184 wheat expressed sequence tags (ESTs) that represent 947 genes. Gene expression during cold acclimation was compared in 2 cultivars with marked differences in freezing tolerance. Transcript levels of more than 300 genes were altered by cold. Among these, 65 genes were regulated differently between the 2 cultivars for at least 1 time point. These include genes that encode potential regulatory proteins and proteins that act in plant metabolism, including protein kinases, putative transcription factors, Ca2+ binding proteins, a Golgi localized protein, an inorganic pyrophosphatase, a cell wall associated hydrolase, and proteins involved in photosynthesis.