Hamster Strain Research Articles

Changes in prion replication environment cause prion strain mutation

Interspecies prion transmission often leads to stable changes in physical and biological features of prion strains, a phenomenon referred to as a strain mutation. It remains unknown whether changes in the replication environment in the absence of changes in PrP primary structure can be a source of strain mutations. To approach this question, RNA content was altered in the course of amplification of hamster strains in serial protein misfolding cyclic amplification (sPMCAb). On adaptation to an RNA-depleted environment and then readaptation to an environment containing RNA, strain 263K gave rise to a novel PrP(Sc) conformation referred to as 263K(R+), which is characterized by very low conformational stability, high sensitivity to proteolytic digestion, and a replication rate of 10(6)-fold/PMCAb round, which exceeded that of 263K by almost 10(4)-fold. A series of PMCAb experiments revealed that 263K(R+) was lacking in brain-derived 263K material, but emerged de novo as a result of changes in RNA content. A similar transformation was also observed for strain Hyper, suggesting that this phenomenon was not limited to 263K. The current work demonstrates that dramatic PrP(Sc) transformations can be induced by changes in the prion replication environment and without changes in PrP primary structure.

Implications of protease activation in cardiac dysfunction and development of genetic cardiomyopathy in hamsters

It has become evident that protein degradation by proteolytic enzymes, known as proteases, is partly responsible for cardiovascular dysfunction in various types of heart disease. Both extracellular and intracellular alterations in proteolytic activities are invariably seen in heart failure associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, hypertensive cardiomyopathy, diabetic cardiomyopathy, and ischemic cardiomyopathy. Genetic cardiomyopathy displayed in different strains of hamsters provides a useful model for studying heart failure due to either cardiac hypertrophy or cardiac dilation. Alterations in the function of several myocardial organelles such as sarcolemma, sarcoplasmic reticulum, myofibrils, mitochondria, as well as extracellular matrix have been shown to be due to subcellular remodeling as a consequence of changes in gene expression and protein content in failing hearts from cardiomyopathic hamsters. In view of the increased activities of various proteases, including calpains and matrix metalloproteinases in the hearts of genetically determined hamsters, it is proposed that the activation of different proteases may also represent an important determinant of subcellular remodeling and cardiac dysfunction associated with genetic cardiomyopathy.

Does the Precision of a Biological Clock Depend upon Its Period? Effects of the Duper and tau Mutations in Syrian Hamsters

Mutations which alter the feedback loops that generate circadian rhythms may provide insight into their insensitivity to perturbation robustness) and their consistency of period (precision). I examined relationships between endogenous period, activity and rest (τDD, α and ρ) in Syrian hamsters using two different mutations, duper and tau, both of which speed up the circadian clock. I generated 8 strains of hamsters that are homozygous or heterozygous for the tau, duper, and wild type alleles in all combinations. The endogenous period of activity onsets among these strains ranged from 17.94+0.04 to 24.13±0.04 h. Contrary to predictions, the variability of period was unrelated to its absolute value: all strains showed similar variability of τDD when activity onsets and acrophase were used as phase markers. The τDD of activity offsets was more variable than onsets but also differed little between genotypes. Cycle variation and precision were not correlated with τDD within any strain, and only weakly correlated when all strains are considered together. Only in animals homozygous for both mutations (super duper hamsters) were cycle variation and precision reduced. Rhythm amplitude differed between strains and was positively correlated with τDD and precision. All genotypes showed negative correlations between α and ρ. This confirms the expectation that deviations in the duration of subjective day and night should offset one another in order to conserve circadian period, even though homeostatic maintenance of energy reserves predicts that longer intervals of activity or rest would be followed by longer durations of rest or activity. Females consistently showed greater variability of the period of activity onset and acrophase, and of α, but variability of the period of offset differed between sexes only in super duper hamsters. Despite the differences between genotypes in τDD, ρ was consistently more strongly correlated with the preceding than the succeeding α.

PK-sensitive PrPSc Is Infectious and Shares Basic Structural Features with PK-resistant PrPSc

One of the main characteristics of the transmissible isoform of the prion protein (PrPSc) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrPSc following Western blot or ELISA. More recently, researchers determined that there is a sizeable fraction of PrPSc that is sensitive to PK hydrolysis (sPrPSc). Our group has previously reported a method to isolate this fraction by centrifugation and showed that it has protein misfolding cyclic amplification (PMCA) converting activity. We compared the infectivity of the sPrPSc versus the PK-resistant (rPrPSc) fractions of PrPSc and analyzed the biochemical characteristics of these fractions under conditions of limited proteolysis. Our results show that sPrPSc and rPrPSc fractions have comparable degrees of infectivity and that although they contain different sized multimers, these multimers share similar structural properties. Furthermore, the PK-sensitive fractions of two hamster strains, 263K and Drowsy (Dy), showed strain-dependent differences in the ratios of the sPrPSc to the rPrPSc forms of PrPSc. Although the sPrPSc and rPrPSc fractions have different resistance to PK-digestion, and have previously been shown to sediment differently, and have a different distribution of multimers, they share a common structure and phenotype.

Correction Isolation and characterization of 16 novel microsatellite loci in two inbred strains of the Chinese hamster (Cricetulus griseus)

Correction Isolation and characterization of 16 novel microsatellite loci in two inbred strains of the Chinese hamster (Cricetulus griseus)

Relationship between Conformational Stability and Amplification Efficiency of Prions

Recent studies demonstrated that the efficiency, rate, and yield of prion amplification in vitro could be substantially improved by supplementing protein misfolding cyclic amplification (PMCA) with Teflon beads [Gonzalez-Montalban et al. (2011) PLoS Pathog. 7, e1001277]. Here we employed the new PMCA format with beads (PMCAb) to gain insight into the mechanism of prion amplification. Using a panel of six hamster prion strains, the effect of beads on amplification was found to be strain-specific, with the largest improvements in efficiency observed for strains with the highest conformational stability. This result suggests a link between PrP(Sc) conformational stability and its fragmentation rate and that beads improved amplification by assisting fragmentation. Furthermore, while exploring the PrP(Sc)-independent bead effect mechanism, a synergy between the effects of RNA and beads on amplification was observed. Consistent with previous studies, amplification of all six hamster strains tested here was found to be RNA-dependent. Under sonication conditions used for PMCA, large RNA molecules were found to degrade into smaller fragments of a size that was previously shown to be the most effective in facilitating prion conversion. We speculate that sonication-induced changes in RNA size distribution could be one of the rate-limiting steps in prion amplification.

Isolation and characterization of 16 novel microsatellite loci in two inbred strains of the Chinese hamster (Cricetulus griseus)

The Shanyi inbred A and E strains of the Chinese hamster are widely used in biomedical research, but detailed genetic characterization has been lacking. We developed microsatellite markers that could be used for genetic diversity analysis and linkage map construction. We isolated and characterized 16 novel microsatellite loci from a microsatellite-enriched genomic DNA library. These loci were genotyped in 48 animals from the two strains, and the polymorphic information content was determined. In the Shanyi A and E populations, 14 and 15 loci were found to be polymorphic, respectively, with polymorphic information content ranging from 0.1393 to 0.8082 and from 0.1109 to 0.7397, respectively. A total of 115 alleles were found for the 16 microsatellite loci in the two populations; the mean observed heterozygosity (H(O)) was 0.5191 and 0.4333 for the A and E populations, respectively, indicating marked genetic variation within the two populations. Correspondingly, the F(ST) values ranged from 0.002 to 0.9253, with an overall mean of 0.1935, indicating significant genetic difference between the two strains. The population differentiation levels were substantiated by Nei's genetic distance and full Bayesian analyses computed with STRUCTURE. Despite the genetic diversity and differentiation within and between the two inbred populations, the 48 individuals were correctly allocated into their original populations with high statistical confidence based on these 16 microsatellite loci. These novel microsatellite loci should be useful genetic markers for these two Chinese hamster inbred strains.

Behavioural and endocrinological changes in Syrian hamsters (Mesocricetus auratus) under domestication

This study aimed to quantify differences in response to stress between two strains of Syrian hamsters to evaluate the consequences of domestication in this species by measuring behavioural traits in the open-field, adrenal gland masses (ADR), and faecal and blood corticosterone concentrations (CC). We studied a laboratory (lab)- and a wild-derived population (wild). The lab hamsters were significant heavier than the wild hamsters. The lab males had the highest ADR, and it was independent of their high body mass (BM). The ADR of lab females and wild hamsters was linearly dependent of BM. The lab males had the highest faecal and blood CC, whereas the lab females had the lowest CC. In the open field, the lab hamsters began later to groom, groomed shorter, groomed less frequently, began later to rear, reared longer and reared less frequently. In the lab population, females reared more often and groomed longer than males. The sex differences in the behaviours of the lab population and the differences between the populations mirror the differences neither in the ADR nor in the CC. The founder effect and the breeding history of lab Syrian hamsters are discussed as causes of the differences between the studied populations.

Ezetimibe Reduces Enlarged Prostate in an Animal Model of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia is a common urinary tract disorder that affects aging men. The molecular mechanisms underlying benign prostatic hyperplasia are obscure and the development of animal models to test novel treatment strategies is challenging. We report that the Bio 87.20 hamster strain (Bio Breeders, Watertown, Massachusetts) shows 5α-reductase-sensitive prostate enlargement and a decrease in circulating cholesterol reduces prostate size. Bio 87.20 hamsters 17 months old with an enlarged prostate were fed a diet containing no or minimal cholesterol and including finasteride (Merck, Whitehouse Station, New Jersey) and/or ezetimibe (Schering-Plough, Kenilworth, New Jersey) for 4 months. The prostate complex was removed, volume and weight were determined, and tissue was examined histologically. Prostate enlargement depended on cholesterol in the diet. Blockade of intestinal cholesterol transport with ezetimibe induced prostate regression to a similar extent as the 5α-reductase inhibitor finasteride, a compound used to treat benign prostatic hyperplasia in humans. Histological analysis indicated that finasteride induced widespread prostatic atrophy but normal glandular architecture was preserved in the ezetimibe cohort. Results indicate that dysregulation of cholesterol metabolism may be a component of benign prostatic hyperplasia and ezetimibe may be effective as an alternative or adjunct to standard treatment. Our findings also show that the Bio 87.20 hamster is a suitable model for preclinical evaluation of novel benign prostatic hyperplasia therapy.

TNF-alpha-mediated signal transduction pathway is a major determinant of apoptosis in dilated cardiomyopathy.

Although J2N-k strain of cardiomyopathic hamsters is an excellent model of dilated cardiomyopathy, the presence and mechanisms of apoptosis in the hearts of these genetically modified animals have not been investigated. This study examined the hypothesis that cardiac dysfunction and apoptosis in the cardiomyopathic hamsters were associated with tumour necrosis factor-alpha (TNF-α)-mediated signalling pathway involving the activation of some pro-apoptotic proteins and/or deactivation of some antiapoptotic proteins. Echocardiographic assessment of 31-week-old hamsters indicated an increase in the internal dimension of the left ventricle as well as decreases in the ejection fraction, fractional shortening and cardiac output without any evidence of cardiac hypertrophy. Increased level of TNF-α and apoptosis in cardiomyopathic hearts were accompanied by increased protein content for protein kinase C (PKC) -α and -ɛ isozymes as well as caspases 3 and 9. Phosphorylated protein content for p38 MAPK and NFκB was increased whereas that for Erk1/2, BAD and Bcl-2 was decreased in cardiomyopathic hearts. These results support the view that TNF-α and PKC isozymes may promote apoptosis due to the activation of p38 MAPK and deactivation of Erk1/2 pathways, and these changes may contribute toward the development of cardiac dysfunction in dilated cardiomyopathy.

Use of hamster as a model to study diet-induced atherosclerosis

Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified) and dietary perturbation (cholesterol and/or fat) on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C) than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA), monounsaturated or n-6 polyunsaturated (PUFA) had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s) of diet-induced development of atherosclerotic lesions.

Involvement of TLR2 in innate response to Bacillus anthracis infection

The involvement of TLR2 receptor in the innate response to infection with Bacillus anthracis was investigated. We studied the response to virulent or attenuated Vollum strains in either in vitro assays using macrophage cultures, or in an in vivo model comparing the sensitivity of Syrian hamster cells (expressing normal TLR2) to Chinese hamster cells (lacking functional TLR2) to infection by the various B. anthracis strains. Phagocytosis experiments with murine cell cultures or primary macrophages from both hamster strains, using virulent or attenuated Tox(+)Cap(-), Tox(-)Cap(+) or Tox(-)Cap(-) spores indicated that the secretion of TNF-alpha was induced by all the bacterial spores and purified spore antigens. In contrast, capsular antigens induce secretion of TNF-alpha only by Syrian hamster macrophages indicating the involvement of a functional TLR2 in macrophage activation. Challenge experiments with both hamster strains by intranasal spore inoculation, indicated that, while both strains are equally sensitive to infection with the virulent strain, the Chinese hamster demonstrated a higher sensitivity to infection with the toxinogenic or encapsulated strains. In conclusion, our findings imply that TLR2 has an important role in the attempt of the innate immunity to control B. anthracis infection, although TNF-alpha secretion was found to be mediated by both TLR2-dependent and TLR2-independent pathways.

Periodic variation in R-R intervals and cardiovascular autonomic regulation in young adult Syrian hamsters

Several hamster strains are commonly used as models for cardiomyopathic phenotypes evolving toward heart failure. However, little is known about heart rate variability (HRV) in this species. Prolonged surface ECG recording, a prerequisite to HRV studies, can be obtained either by telemetry or by restraints. Here, we performed long time ECG recording using telemetry on young adult Syrian hamsters and we analyzed time series of interbeat intervals. Standard statistics showed that the mean of normal R-R intervals slightly increased with age, with standard deviation of normal R-R intervals remaining stable over time. However, time domain analysis using Poincaré plots revealed dynamic changes in the HRV. Analysis of frequency domains revealed that the ratio of spectral components (low frequency/high frequency) exhibited a maturation pattern. Thus refined analysis of HRV revealed a more complex pattern than common statistical analysis would translate. Unlike other rodents, hamsters display a great spontaneous variability of their heart rate. As the complexity canvas of HRV might be the consequence of extracardiac regulation factors, we assessed the sympathovagal balance in both time and frequency domain of heart rate. Pharmacological tests revealed that both sympathetic and vagal tones contribute to HRV in Syrian hamsters. Thus Syrian hamsters have a broad intrinsic HRV with large influences of the neurovegetative system. However, the influence of the previous beat seems to prevail over the autonomic oscillators. These animals present a high sensitivity to artificially altered cardiac regulation and might be great models for the diagnosis of early alterations in the HRV related to pathology. Therefore, Syrian hamsters represent a unique model for HRV studies.

77 SUCCESSFUL CRYOPRESERVATION OF SYRIAN HAMSTER OVARIES BY VITRIFICATION

In place of gametes, ovaries can be used as an alternative resource for cryopreservation. At the previous IETS meeting, we showed that in the Syrian hamster, pups could be successfully produced through the transplantation of fresh ovaries. In addition, the immunotolerance of interstrain ovarian transplantation was described. In this study, we attempted to produce pups via transplantation of cryopreserved ovaries to foster mothers. Our goal was to establish a preservation method for hamster strains based on ovarian cryopreservation in combination with ovarian transfer. Ovaries were cryopreserved by vitrification according to methods described for mouse ovaries (Migishima F et al. 2003 Biol. Reprod. 68, 881–887). In brief, ovaries were collected from 2- to 3-week-old HAW strain (white coat) females. Each ovary was cut into 4 sections, placed into 1 tube, and cryopreserved by vitrification using DAP213 solution (2 m dimethyl sulfoxide, 1 m acetamide, and 3 m propylene glycol; Nakagata N 1989 J. Reprod. Fertil. 87, 479–483). Thawed ovaries were transferred into the ovarian bursae (2 ovarian sections per ovarian bursa) of 3-week-old recipient females with agouti coat (Slc:Syrian) under anesthesia with isoflurane. Half of the recipients’ ovaries were removed immediately before transfer; i.e. both donor and recipient ovaries were present in each ovarian bursa. Successful ovarian transplantation was verified by examining the coat color (non-agouti color) of offspring produced in test matings between mature recipients and Slc:Syrian males. Out of 6 recipients tested, 2 became pregnant and delivered pups. According to the coat color of the pups, 1 of the 2 recipients delivered a pup produced from transplanted ovaries (1 out of 4 pups). Regardless of this low success rate, our results indicate that pups can be produced from cryopreserved ovaries via interstrain transplantation of ovaries to foster mothers in the Syrian hamster. Thus, ovarian cryopreservation by vitrification is a promising strategy for strain preservation of the Syrian hamster. This work was supported by a grant from the Ministry of Health, Labor, and Welfare, Japan.

148 PRODUCTION OF PUPS BY OVARIAN TRANSFER IN THE SYRIAN HAMSTER

Instead of gametes, ovaries could be used as alternative resources for cryopreservation. In this study, we attempted to produce pups by transplantation of fresh ovaries to foster mothers as a first step to establish a preservation method of hamster strains on the basis of the cryopreservation of ovaries in combination with ovarian transfers. We also checked the possibility of inter-strain transfers of ovaries, since immunological tolerance among hamster strains is suggested by the fact that most Syrian hamsters were derived from only a small number of animals. Fresh ovaries collected from 3-weekold females of HAW (white coat) and APA (albino) strains were transferred into ovarian bursae of 3-week-old recipient females with agouti-coat (Slc:Syrian) under anesthesia with xylazine and ketamine. Halves of ovaries of recipients were removed immediately before the transfers, i.e., both donor and recipient ovaries were present in each ovarian bursa. Successful transplantation of ovaries was checked by the coat color (non-agouti color) of offspring produced by test matings of recipients with Slc:Syrian males after the recipients became mature. Five and six recipients received HAW and APA ovaries, respectively. All 11 recipients tested became pregnant and delivered pups. According to the coat color of the pups, three of five recipients which received HAW ovaries and one of six recipients which received APA ovaries delivered pups derived from transplanted ovaries (two out of eight pups, one out of seven pups, and three out of 11 pups for HAW; one out of five pups for APA). Our results indicate that transplantation of fresh ovaries to foster mothers could be used for production of pups from grafted ovaries in the Syrian hamster. In particular, immunological tolerance for ovarian transfers among at least three strains suggests that recipient strains might not need to be the same as donor strains for practical ovarian transfers in the Syrian hamster. Our results would facilitate the development of a strain preservation system for the Syrian hamster based on ovarian cryopreservation. This work was supported by a grant from the Ministry of Health, Labor, and Welfare of Japan.

Bio F1B hamster: a unique animal model with reduced lipoprotein lipase activity to investigate nutrient mediated regulation of lipoprotein metabolism

BackgroundBio F1B hamster is an inbred hybrid strain that is highly susceptible to diet-induced atherosclerosis. We previously reported that feeding a high fat fish oil diet to Bio F1B hamster caused severe hyperlipidaemia. In this study we compared the effects of various diets in the Bio F1B hamster and the Golden Syrian hamster, which is an outbred hamster strain to investigate whether genetic background plays an important role in dietary fat mediated regulation of lipoprotein metabolism. We further investigated the mechanisms behind diet-induced hyperlipidaemia in F1B hamster.MethodsThe Bio F1B and Golden Syrian hamsters, 8 weeks old, were fed high fat diets rich in either monounsaturated fatty acids, an n-6: n-3 ratio of 5 or a fish oil diet for 4 weeks. Animals were fasted overnight and blood and tissue samples were collected. Plasma was fractionated into various lipoprotein fractions and assayed for triacylglycerol and cholesterol concentrations. Plasma lipoprotein lipase activity was measured using radioisotope method. Microsomal triglyceride transfer protein activity was measured in the liver and intestine. Plasma apolipoproteinB48, -B100 and apolipoprotein E was measured using Western blots. Two-way ANOVA was used to determine the effect of diet type and animal strain.ResultsThe fish oil fed F1B hamsters showed milky plasma after a 14-hour fast. Fish oil feeding caused accumulation of apolipoproteinB48 containing lipoprotein particles suggesting hindrance of triglyceride-rich lipoprotein clearance. There was no significant effect of diet or strain on hepatic or intestinal microsomal triglyceride transfer protein activity indicating that hyperlipidaemia is not due to an increase in the assembly or secretion of lipoprotein particles. F1B hamsters showed significantly reduced levels of lipoprotein lipase activity, which was inhibited by fish oil feeding.ConclusionEvidence is presented for the first time that alterations in lipoprotein lipase activity and mRNA levels contribute to varied response of these hamsters to dietary fat, highlighting the importance of genetic background in the regulation of lipid and lipoprotein metabolism by dietary fats. Bio F1B hamster may prove to be an important animal model to investigate nutrient mediated regulation of metabolic parameters under lipoprotein lipase deficiency.

T.O. 6 Systemic delta-sarcoglycan gene transfer into cardiomyopathic BIO14.6 hamsters by AAV

The delta-sarcoglycan (delta-SG) deficient Syrian hamster strain BIO14.6 is one the most used animal model for human primitive cardiomyopathy and muscular dystrophy. The main goal of our project is a rescue of cardiac and muscular functionality of BIO14.6 hamsters using adeno-associated viral (AAV) vectors injection. We observed that therapy could be much more successful in younger animals (16 days old BIO14.6 hamsters), in which we injected 2×1012 GC of the AAV2/8 vector expressing the human delta-SG.

Short‐term treatment using insulin‐like growth factor‐1 (IGF‐1) improves life expectancy of the delta‐sarcoglycan deficient hamster

The hamster strain CHF147 presents a progressive dilated cardiomyopathy (DCM) due to a large deletion of the delta-sarcoglycan gene that leads to heart failure. This cardiomyopathy induces premature death. We have previously shown that a short-term treatment using IGF-1 preserves cardiac structure and improves function of the CHF147 hamster. In the current study, we measured long-term effects of short-term treatment with recombinant human IGF-1 (rhIGF-1) in CHF147 hamsters. CHF147 hamsters (7-8 months old) were implanted under the skin with an osmotic pump filled either with saline or with recombinant human IGF-1 at a total dose of 25 microg. The osmotic pump allowed a continuous delivery of the protein for a mean duration of 19 days. We observed a significant increase in overall survival, as well as preservation of cardiac function, in the rhIGF-1-treated group. At the time of death, hearts of treated animals did not present any macroscopical or histological differences compared to those of sham hamsters. These results show that rhIGF-1 treatment slows down the evolution of the DCM in the CHF147 hamster. Moreover, the low dose treatment did not increase IGF-1 serum levels. This study is the first one reporting beneficial effects of IGF-1 treatment on survival of an animal model presenting DCM. Our results raise hopes for a new therapeutic approach of this pathology.

Predisposition to Hypertension in a Strain of Hamsters Influences Muscle Adaptations to Exercise Training

PURPOSE: In an attempt to characterize the influence of hypertension on training adaptations to skeletal muscle, colonies of normotensive and spontaneously hypertensive hamsters were studied following 6 weeks of either resistance or endurance exercise training protocols. METHODS: Normotensive and hypertensive animals were randomly assigned to different training programs. Resistance trained animals (RN, RH) underwent surgical ablation and proximal suturing of the gastrocnemius contribution to the triceps surae tendon to induce atrophy in medial (MG) and lateral (LG) gastrocnemius fibers and compensatory hypertrophy in the soleus (S) and plantaris (P) muscles. Endurance trained animals (EN, EH) were subjected to 6 weeks of progressive treadmill training. Six weeks following intervention, animals were sacrificed, and S, P, MG and LG samples were collected and analyzed for myosin heavy chain (MHC) expression, fiber cross-sectional area (CSA), and capillary-to-fiber (C/F) ratio. RESULTS: Among the major findings of this study, spontaneously hypertensive animals showed greater responses to resistance training; while both RN and RH showed significant hypertrophy of S and P muscles, increases in fiber CSA were significantly greater in RH muscle. In contrast, whereas C/F ratio increased to comparable degrees in EN and EH for P muscle, final values of C/F ratio were twice as great in EN S compared to EH S muscle, suggesting a better response to endurance training in normotensive animals. Additional differences were observed when fibers were categorized according to MHC content. CONCLUSIONS: Predisposition to hypertension has a substantial influence on skeletal muscle adaptations to exercise in the animal model used in the present study. If applicable to hypertensive influences in humans, these results have major implications for exercise prescriptions as therapy for hypertension.

Heart Failure: A Silver bullet to treat heart failure

Heart failure (HF) continues to be a progressive disease with ever increasing morbidity and mortality in the western world.1 While progress in conventional treatment modalities is making steady and incremental gains to reduce HF mortality, there remains a need to explore new and potentially therapeutic approaches.1 To that end, several animal models of heart failure have been used to test these novel therapies. A genetic strain of Syrian hamsters with a large deletion in the -sarcoglycan (SG) gene (TO-2 strain), are characterized by skeletal muscle myopathy, and severe cardiac dilation and cardiomyopathy, which primarily contributes to the very high mortality in these animals.2 In a recent study, Zhu et al.3 reported that a single injection of adeno-associated type-8 vector carrying the human -SG gene enhanced contractile function in the hearts of these diseased hamsters, restored exercise capacity and survival to normal, and improved skeletal muscle function.