Conservation and management of hydromyine rodents in Victoria, Australia

Of the 15 species of native rodents recorded from Victoria, Australia, six became extinct within 70 years of European settlement, and two of the remaining nine are classified as ‘threatened’ and four are classified as ‘near threatened’. Thus, only three species are considered to be adequately conserved. This represents one of the most dramatic mammalian species declines recorded in Australia. All the threatened species belong to the subfamily Hydromyinae, the Australian ‘old endemics’. Of the extinct species, four were recorded only from the semi-arid north-west of the state and two from dry woodlands in the central and southern regions. The two  endangered species are the smoky mouse, which has a disjunct distribution from near-coastal to sub-alpine habitats, and the New Holland mouse, which is the most geographically restricted species. Discovered in Victoria only in 1970, it has become extinct at several locations and is the subject of a major recovery program that includes captive breeding and reintroduction. Conservation protocols and practices for Victoria’s native rodents are implemented under state legislation, but lack of basic ecological information makes their conservation a difficult task.

Natriuretic peptides : do they regulate water balance in desert-adapted rodents?

This research determined how the natriuretic peptide system, which controls water and salt balance, responds to water limitation in a desert rodent. It was found that a uniform down-regulation of the system is not part of the physiological response to minimise water loss during periods of low water availability.

Exploration strategies map along fast-slow metabolic and life-history continua in muroid rodents

1Personality is highly relevant to ecology and the evolution of fast–slow metabolic and life-history strategies. One of the most important personality traits is exploratory behaviour, usually measured on an animal introduced to a novel environment (e.g. open-field test).2Here, we use a unique comparative dataset on open-field exploratory behaviour of muroid rodents to test a key assumption of a recent evolutionary model, i.e. that exploration thoroughness is positively correlated to age at first reproduction (AFR). We then examine how AFR and exploratory behaviour are related to basal metabolic rate (BMR).3Inter-specific variation in exploratory behaviour was positively correlated with AFR. Both AFR and exploration behaviour were negatively correlated with BMR. These results remained significant when taking phylogeny into account.4We suggest that species occupying unproductive and unpredictable environments simultaneously benefit from high exploration, low BMR and delayed AFR because exploration increases the likelihood of finding scarce resources, whereas low BMR and delayed reproduction enhance survival during frequent resources shortages.5This study provides the first empirical evidence for a link between personality, life-history, phylogeny and energy metabolism at the inter-specific level. The superficial-thorough exploration continuum can be mapped along the fast–slow metabolic and life-history continua.

Camera trapping: a contemporary approach to monitoring invasive rodents in high conservation priority ecosystems

Invasive rodent species have established on 80% of the world's islands causing significant damage to island environments. Insular ecosystems support proportionally more biodiversity than comparative mainland areas, highlighting them as critical for global biodiversity conservation. Few techniques currently exist to adequately detect, with high confidence, species that are trap-adverse such as the black rat, Rattus rattus, in high conservation priority areas where multiple non-target species persist. This study investigates the effectiveness of camera trapping for monitoring invasive rodents in high conservation areas, and the influence of habitat features and density of colonial-nesting seabirds on rodent relative activity levels to provide insights into their potential impacts. A total of 276 camera sites were established and left in situ for 8 days. Identified species were recorded in discrete 15 min intervals, referred to as 'events'. In total, 19 804 events were recorded. From these, 31 species were identified comprising 25 native species and six introduced. Two introduced rodent species were detected: the black rat (90% of sites), and house mouse Mus musculus (56% of sites). Rodent activity of both black rats and house mice were positively associated with the structural density of habitats. Density of seabird burrows was not strongly associated with relative activity levels of rodents, yet rodents were still present in these areas. Camera trapping enabled a large number of rodents to be detected with confidence in site-specific absences and high resolution to quantify relative activity levels. This method enables detection of multiple species simultaneously with low impact (for both target and non-target individuals); an ideal strategy for monitoring trap-adverse invasive rodents in high conservation areas.

The regulation of glucose metabolism: implications and considerations for the assessment of glucose homeostasis in rodents

 The incidence of insulin resistance and type 2 diabetes (T2D) is increasing at alarming rates. In the quest to understand the underlying causes of and to identify novel therapeutic targets to treat T2D, scientists have become increasingly reliant on the use of rodent models. Here, we provide a discussion on the regulation of rodent glucose metabolism, highlighting key differences and similarities that exist between rodents and humans. In addition, some of the issues and considerations associated with assessing glucose homeostasis and insulin action are outlined. We also discuss the role of the liver vs. skeletal muscle in regulating whole body glucose metabolism in rodents, emphasizing the importance of defective hepatic glucose metabolism in the development of impaired glucose tolerance, insulin resistance, and T2D. © 2014 the American Physiological Society.

Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkâ

Focuses on the reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IkB kinase beta (IKKbeta) Definition of insulin resistance; Recognition of the IKKbeta pathway as the target for insulin sensitization; Impact of the increase of IKKbeta activity on obese rodents.

Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimers disease, across the blood-brain

Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza (Danshen), is widely used in the treatment of coronary heart disease, stroke and less commonly Alzheimer's disease. Our recent study indicates that CTS is a substrate for Pglycoprotein (PgP/MDR1/ABCB1). This study has investigated the nature of the brain distribution of CTS across the brain-blood barrier (BBB) using several in vitro and in vivo rodent models. A polarized transport of CTS was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with facilitated efflux from the abluminal side to luminal side. Addition of a PgP (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2) inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides attenuated the polarized transport. In a bilateral in situ brain perfusion model, the uptake of CTS into the cerebrum increased from 0.52 ± 0.1% at 1 min to 11.13 ± 2.36 ml/100 g tissue at 30 min and was significantly greater than that of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g. probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%. The brain levels of CTS were only about 21% of those in plasma, and were significantly increased when coadministered with verapamil or probenecid in rats. The brain levels of CTS in rats subjected to middle cerebral artery occlusion and rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-) mice were 10.9- and 1.5-fold higher than those in the wild-type mice, respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit the brain penetration of CTS in rodents, suggesting a possible role of PgP and MRP1 in limiting the brain penetration of CTS in patients and causing drug resistance to Danshen therapy and interactions with conventional drugs that are substrates of PgP and MRP1. Further studies are needed to explore the role of other drug transporters in restricting the brain penetration of CTS and the clinical relevance.

The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-Kinase in cultured skeletal muscle of obese humans

Context: Leptin is thought to regulate whole-body adiposity and insulin sensitivity, at least in part, by stimulating fatty acid metabolism via activation of AMP-kinase (AMPK) in skeletal muscle. Human obesity is associated with leptin resistance, and recent studies have demonstrated that hypothalamic expression of the suppressors of cytokine signaling 3 (SOCS3) regulates leptin sensitivity in rodents.

Objective: The objective of the study was to investigate the effects of leptin on fatty acid oxidation and AMPK signaling in primary myotubes derived from lean and obese skeletal muscle and evaluate the contribution of SOCS3 to leptin resistance and AMPK signaling in obese humans.

Results: We demonstrate that leptin stimulates AMPK activity and increases AMPK Thr172 and acetyl-CoA carboxylase-ß Ser222 phosphorylation and fatty acid oxidation in lean myotubes but that in obese subjects leptin-dependent AMPK signaling and fatty acid oxidation are suppressed. Reduced activation of AMPK was associated with elevated expression of IL-6 (~3.5-fold) and SOCS3 mRNA (~2.5-fold) in myotubes of obese subjects. Overexpression of SOCS3 via adenovirus-mediated infection in lean myotubes to a similar degree as observed in obese myotubes prevented leptin but not AICAR (5-amino-imidazole-4-carboxamide-1-ß-D-ribofuranoside) activation of AMPK signaling.

Conclusions: These data demonstrate that SOCS3 inhibits leptin activation of AMPK. These data suggest that this impairment of leptin signaling in skeletal muscle may contribute to the aberrant regulation of fatty acid metabolism observed in obesity and that pharmacological activation of AMPK may be an effective therapy to bypass SOCS3-mediated skeletal muscle leptin resistance for the treatment of obesity-related disorders.

Effect of 2 weeks of endurance training on uncoupling protein3 content in untrained human subjects

Aim: The mitochondrial uncoupling protein-3 (UCP3) is able to lower the proton gradient across the inner mitochondrial membrane, thereby uncoupling substrate oxidation from ATP production and dissipating energy as heat. What the effect of endurance training on UCP3 is, is still  controversial. Endurance-trained athletes are characterized by lower levels of UCP3, but longitudinal studies in rodents reported no effect of endurance training on muscular UCP3 levels. Here, we examined the effect of a 2-week training programme on skeletal muscle UCP3 protein content in untrained human subjects, and hypothesized that UCP3 will be reduced after the training programme. Methods: Nine untrained men [age: 23.3±3.2 years; BMI: 22.6±2.6 kg m^-2; maximal power output (^Wmax): 3.8±0.6 W kg^-1 body weight] trained for 2 weeks. Before and at least 72 h after the training period, muscle biopsies were taken for determination of UCP3 protein content. Results: UCP3 protein content tended to be lower after the training programme [95±10 vs. 109±12 arbitrary units (AU), P= 0.08]. Cytochrome c content tended to increase with 33% in response to endurance training (52± 6 vs. 39± 6 AU, P = 0.08). The ratio UCP3 relative to cytochrome c tended to decrease significantly upon endurance training (2.0±0.4 vs. 3.2±0.6 AU, P = 0.01). Conclusion: A short-term (2-week) endurance training programme decreased UCP3 protein levels and significantly reduced the ratio of UCP3 to cytochrome c.

Ecological fire regimes for the recovery and management of threatened small mammals in southern Australia

The application of fire to fauna management, particularly for endangered species, is a significant issue for wildlife managers. Mammals respond to fire regimes including intensity, frequency and season of occurrence, and changes in fire-regimes are implicated in detrimental effects on mammal communities. For many species temporal habitat change is a key factor affecting the persistence of populations. These species require the option of colonising the shifting habitat mosaic. There is substantial evidence that species such as the native rodents New Holland Mouse (Pseudomys novaehollandiae) and Heath Rat (Pseudomys shortridgei) are early successional species dependent on such temporal habitat changes. In conrast species such as the dasyurid marsupial, Swamp Antechinus (Antechinus minimus) are late successional species, which may take up to 20 years to recolonise. In many situations ecological fire regimes need to be implemented to increase areas of suitable habitat for population expansion and reintroductions. This paper assesses research findings and the development of management actions incorporating ecological fire regimes for the recovery of Pseudomyine rodents and the Swamp Antechinus. Spatially explicit models are required to determine changes and patterns at the landscape level. The prospect of global climate change also is of significance and needs to be assessed.

A reservoir of brown adipocyte progenitors in human skeletal muscle

Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-{gamma} (PPAR{gamma}) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPAR{gamma} agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.

The effect of water deprivation on the tonicity responsive enhancer binding protein (TonEBP) and TonEBP-regulated genes in the kidney of the spinifex hopping mouse, Notomys alexis

In desert rodents, the production of concentrated urine is essential for survival in xeric environments in order to conserve water. Reabsorption of water in the kidney is dependent on large osmotic gradients in the renal medulla. This causes the renal cells to be bathed in a hypertonic extracellular fluid that can compromise cellular function. In response to hypertonicity, kidney cells accumulate compatible, non-ionic osmolytes that lower the ionic strength within the cells to isotonic levels by replacing intracellular ionic electrolytes. The tonicity-responsive enhancer binding protein (TonEBP) is a transcription factor that regulates the expression of genes that encode proteins that catalyse the accumulation of compatible osmolytes. We investigated the expression of TonEBP mRNA and protein and compatible osmolyte genes in the Spinifex hopping mouse, Notomys alexis, an Australian desert rodent that produces a highly concentrated urine. TonEBP mRNA expression was unchanged after 3 days of water deprivation but was significantly increased after 7 and 14 days of water deprivation. Immunohistochemistry showed that during water deprivation TonEBP had translocated from the cytoplasm into the nucleus of cells in the renal medulla and papilla. In addition, 3, 7 and 14 days of water deprivation caused a significant increase in aldose reductase (AR), myo-inositol (SMIT), betaine/GABA (BGT-1) and taurine (TauT) transporter mRNA expression, which is indicative of an increase in TonEBP activity. In desert rodents, TonEBP regulation of gene transcription is probably an important mechanism to protect renal cells in the face of the large corticomedullary gradient that is required to concentrate urine and conserve water.

Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle

• 1. The present review discusses the potential role of nitric oxide (NO) in the: (i) regulation of skeletal muscle glucose uptake during exercise; and (ii) activation of mitochondrial biogenesis after exercise.
• 2. We have shown in humans that local infusion of an NO synthase inhibitor during exercise attenuates increases in skeletal muscle glucose uptake without affecting blood flow. Recent studies from our laboratory in rodents support these findings in humans, although rodent studies from other laboratories have yielded conflicting results.
• 3. There is clear evidence that NO increases mitochondrial biogenesis in non-contracting cells and that NO influences basal skeletal muscle mitochondrial biogenesis. However, there have been few studies examining the potential role of NO in the activation of mitochondrial biogenesis following an acute bout of exercise or in response to exercise training. Early indications are that NO is not involved in regulating the increase in mitochondrial biogenesis that occurs in response to exercise.
• 4. Exercise is considered the best prevention and treatment option for diabetes, but unfortunately many people with diabetes do not or cannot exercise regularly. Alternative therapies are therefore critical to effectively manage diabetes. If skeletal muscle NO is found to play an important role in regulating glucose uptake and/or mitochondrial biogenesis, pharmaceutical agents designed to mimic these effects of exercise may improve glycaemic control.