Sex-specific dysregulation of cardiac-enriched microRNAs with age in .

Dysregulation of cardiac-enriched microRNA (miRNA) expression is linked to age-associated cardiovascular diseases (CVDs). However, the sex-specificity and age at which dysregulation occurs remain unclear. Given the conserved nature of miRNAs and short lifespan of (fruit flies), we investigated age-related changes in the expression of cardiac enriched miRNAs (miR-1, -9, -34a, and -133, target miRNAs) and their impact on the cardiac tube in male and female flies.

MuscleMap: An Open-Source, Community-Supported Consortium for Whole-Body Quantitative MRI of Muscle.

Disorders affecting the neurological and musculoskeletal systems represent international health priorities. A significant impediment to progress in trials of new therapies is the absence of responsive, objective, and valid outcome measures sensitive to early disease changes. A key finding in individuals with neuromuscular and musculoskeletal disorders is the compositional changes to muscles, evinced by the expression of fatty infiltrates.

New tools for the investigation of muscle fiber-type spatial distributions across histological sections.

Background: The functional and metabolic properties of skeletal muscles are partly a function of the spatial arrangement of fibers across the muscle belly. Many muscles feature a non-uniform spatial pattern of fiber types, and alterations to the arrangement can reflect age or disease and correlate with changes in muscle mass and strength. Despite the significance of this event, descriptions of spatial fiber-type distributions across a muscle section are mainly provided qualitatively, by eye.

Use of a novel technique to assess impact of age-related denervation on mouse soleus muscle function.

Denervation contributes to loss of force-generating capacity in aged skeletal muscles, but problems with quantification of denervated fibers mean the precise impact of denervation on muscle function remains unclear. This study therefore looked to develop a reliable assay for identifying denervated muscle fibers, and used this to explore the impact of denervation on age-related force-generation in mouse skeletal muscle. Thirteen young (6-month-old) and 10 old (24-months-old) C57Bl/6 J female mice were utilized.

Age-related structural changes show that loss of fibers is not a significant contributor to muscle atrophy in old mice.

Age-related loss of skeletal muscle mass is widely considered a consequence of both fiber atrophy and fiber death. Evidence for fiber death derives largely from an age-related reduction in fiber numbers in muscle cross-sections, however it is unclear how age-related alterations in muscle morphology affect accuracy of such counts. To explore this we performed an examination of muscle and tendon length, muscle mass and girth, and pennation angle, in addition to histological section fiber counts of parallel-fibered (sternomastoid), fusiform (biceps brachii), and pennate (tibialis anterior, extensor digitorum longus, soleus) muscles from 31 mice aged 6-32 months.

Age-related remodelling of the myotendinous junction in the mouse soleus muscle.

The age-related loss of muscle mass and function predominantly affect muscles of the lower limbs and have largely been associated with decline in muscle fibre size and number, although the exact mechanisms underlying these losses are poorly understood. In addition, consistent reports that the loss of muscle strength exceeds that which can be explained by declines in muscle mass has widened the search for causes of sarcopenia to include supporting tissues such as the extracellular matrix and tendons. Although the changes to both muscle and tendon with age are well characterised, little work has focused on the interface between these two tissues, the myotendinous junction (MTJ).

Modelling dichotomously marked muscle fibre configurations.

Human skeletal muscle consists of contractile elements (fibres) that may be differentiated according to their physiological and biochemical properties. The different types of fibre are distributed throughout each muscle, with the pattern (when viewed as a cross-section) of cell distribution being an important determinant of the functional properties of each muscle. It is well known that the proportions and distributions of muscle fibre types change with advancing age or disease, but few studies have quantitatively investigated these changes.

Age-related loss of muscle fibres is highly variable amongst mouse skeletal muscles.

Sarcopenia is the age-related loss of skeletal muscle mass and strength, attributable in part to muscle fibre loss. We are currently unable to prevent fibre loss because we do not know what causes it. To provide a platform from which to better understand the causes of muscle fibre death we have quantified fibre loss in several muscles of aged C57Bl/6J mice.

Investigation of neuromuscular abnormalities in neurotrophin-3-deficient mice.

Neurotrophin-3 (NT-3) is a trophic factor that is essential for the normal development and maintenance of proprioceptive sensory neurons and is widely implicated as an important modulator of synaptic function and development. We have previously found that animals lacking NT-3 have a number of structural abnormalities in peripheral nerves and skeletal muscles. Here we investigated whether haploinsufficiency-induced reduction in NT-3 resulted in impaired neuromuscular performance and synaptic function.

Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins, a reduced extent of myelination and increased apoptosis of Schwann cells.

This work investigates the role of NT-3 in peripheral myelination. Recent articles, based in vitro, propose that NT-3 acting through its high-affinity receptor TrkC may act to inhibit myelin formation by enhancing Schwann cell motility and/or migration. Here, we investigate this hypothesis in vivo by examining myelination formation in NT-3 mutant mice.

Nerve growth factor mRNA expression in the regenerating antler tip of red deer (Cervus elaphus).

Deer antlers are the only mammalian organs that can fully regenerate each year. During their growth phase, antlers of red deer extend at a rate of approximately 10 mm/day, a growth rate matched by the antler nerves. It was demonstrated in a previous study that extracts from deer velvet antler can promote neurite outgrowth from neural explants, suggesting a possible role for Nerve Growth Factor (NGF) in antler innervation.

Change in mitochondrial membrane potential is the key mechanism in early warm hepatic ischemia-reperfusion injury.

The mitochondrion has been proposed to be both a target and a perpetuator of hepatic ischemia-reperfusion (IR) injury because of its reactive oxygen species (ROS) formation. Our hypothesis is that subcellular derangement in mitochondrial function is one of the earliest steps leading to the early IR-mediated loss of hepatocellular integrity. Under chloralhydrate anesthesia (36 mg/kg BW), Sprague-Dawley rats (n=7) were subjected to 40 min of warm hepatic lobular ischemia followed by 60 min reperfusion.

Neurotrophin-3 null mutant mice display a postnatal motor neuropathy.

This paper examines early postnatal development of the neuromuscular system in mice with a null mutation in the gene for neurotrophin-3. We report that alpha-motoneurons at first develop substantially normally, despite a known 15% deficit in their somal size [Woolley et al. (1999)Neurosci.

Development of a mammalian series-fibered muscle.

This study examines the processes by which multiply innervated, serially fibered mammalian muscles are constructed during development. We previously reported that primary myotubes of such a muscle, the guinea pig sternomastoid muscle, span from tendon to tendon and are innervated at each of the muscle's four innervation zones. Secondary myotubes form later, in association with each point of innervation (Duxson and Sheard, Dev.

Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat.

Background/aims: Hepatic stellate cells (HSCs) are known to play a role in hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC activation at various times after 70% partial hepatectomy (PHx) in the rat.

Methods: The hepatic microcirculation was studied using intravital fluorescence microscopy (IVFM).

Adrenalectomy-induced cell death in the dentate gyrus: further characterisation using TUNEL and effects of the Ginkgo biloba extract, EGb 761, and ginkgolide B.

This study investigated the potential neuroprotective effects of the Ginkgo biloba extract, EGb-761, and ginkgolide B, on adrenalectomy (ADX)-induced cell death in the dentate gyrus (DG). Adrenalectomised, sham surgery-treated, and naive controls received either EGb-761 (25, 50, or 100 mg/kg), 0.9% saline vehicle control, ginkgolide B (10 or 25 mg/kg), or a polyethylene glycol vehicle control, i.

Distribution of neurotrophin receptors in the mouse neuromuscular system.

The neurotrophins are a family of secreted proteins with critical roles in regulation of many aspects of neural development, survival and maintenance. Their actions on neural tissue are thought to be mediated by interaction with high affinity (trk family members) or low affinity (p75NTR) cell surface receptors. In general, neurotrophins are considered to be supplied in limiting quantity by cells of a target tissue or synaptic partner.

Localization of alpha 7 integrins and dystrophin suggests potential for both lateral and longitudinal transmission of tension in large mammalian muscles.

Non-primate mammalian muscles with fascicles above 35 mm in length are composed predominantly of arrays of short, non-spanning muscle fibres, which terminate within the belly of the muscle fascicle at one or both ends. We have previously described the morphological form of various muscle-to-muscle and muscle-to-matrix junctions which are likely involved in tension transmission within one such muscle - the guinea pig sternomastoid muscle (Young et al. 2000).