Effect of regular swimming exercise to duration-intensity on neurocognitive function in cerebral infarction rat model

Objective: This study investigated the effect of regular swimming exercise according to the duration-intensity on neurocognitive function in a cerebral infarction rat model.

Methods: Forty male Sprague–Dawley 10-week-old rats, weighing 300 ± 50 g, were subjected to photothrombotic cerebral infarction. The remaining 36 rats were randomly divided into four groups (n = 9 per group: non-exercise (group A); swimming exercise of short duration-intensity (5 min/day, group B); swimming exercise of moderate duration-intensity (10 min/day, group C); and swimming exercise of long duration-intensity (20 min/day, group D). Exercise was performed five times a week for 4 weeks, beginning the day after cerebral infarction. Neurocognitive function was evaluated with the Morris water maze test. Immunohistochemistry and western blot analysis examined brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) at 4 weeks postinfarction.

Results: At 4 weeks postinfarction, escape latency was found to be shorter in group C than in any of groups A, B, or D. Immunohistochemistry revealed the most significant immunoreactivity for BDNF and VEGF in group C. Western blot analysis demonstrated that BDNF and VEGF proteins were markedly expressed in group C.

Conclusions: Regular swimming exercise of moderate duration-intensity may be the most effective exercise protocol for the recovery of neurocognitive function in cerebral infarction rat model.     

Effects of a summer school-readiness programme on measures of literacy and behaviour growth: a pilot study

Young children enter kindergarten with varying levels of readiness and abilities to learn. One factor that contributes to lower levels of school readiness is poverty. One timely, cost-effective, and feasible strategy to boost school readiness, regardless of exposure to high-quality preschool is to leverage the summer months prior to kindergarten entry and provide comprehensive, evidence-based programming immediately before the school year begins. The current study implemented a community-based summer programme targeted at improving school readiness for 25 four- and five-year-old children in a low-income community. Across the 9-week study, children participated in two types of early literacy activities and the Incredible Years social/emotional learning curriculum. Results indicate that participants demonstrated significant growth across three early literacy skills and were rated as overall stable regarding their behaviour across the summer. These results are discussed along with implications and future directions in this line of research.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit skeletal muscle growth (for review, see ref. 1). Mice lacking MSTN exhibit dramatic increases in muscle mass throughout the body, with individual muscles growing to about twice the normal size (2). MSTN appears to play two distinct roles in regulating muscle size, one to regulate the number of muscle fibers that are formed during development and a second to regulate the growth of those fibers postnatally. The sequence of MSTN has been highly conserved through evolution, with the mature MSTN peptide being identical in species as divergent as humans and turkeys (3). The function of MSTN has also been conserved, and targeted or naturally occurring mutations in MSTN have been shown to cause increased muscling in numerous species, including cattle (3–5), sheep (6), dogs (7), rabbits (8), rats (9), swine (10), goats (11), and humans (12). Numerous pharmaceutical and biotechnology companies have developed biologic agents capable of blocking MSTN activity, and these have been tested in clinical trials for a wide range of indications, including Duchenne and facioscapulohumeral muscular dystrophy, inclusion body myositis, muscle atrophy following falls and hip fracture surgery, age-related sarcopenia, Charcot–Marie–Tooth disease, and cachexia due to chronic obstructive pulmonary disease, end-stage kidney disease, and cancer.The finding that certain inhibitors of MSTN signaling can increase muscle mass even in Mstn^−/− mice revealed that the function of MSTN as a negative regulator of muscle mass is partially redundant with at least one other TGF-β family member (13, 14), and subsequent studies have identified activin A as one of these cooperating ligands (15, 16). MSTN and activin A share many key regulatory and signaling components. For example, the activities of both MSTN and activin A can be modulated extracellularly by naturally occurring inhibitory binding proteins, including follistatin (17, 18) and the follistatin-related protein, FSTL-3 or FLRG (19, 20). Moreover, MSTN and activin A also appear to share receptor components. Based on in vitro studies, MSTN is capable of binding initially to the activin type II receptors, ACVR2 and ACVR2B (also called ActRIIA and ActRIIB) (18) followed by engagement of the type I receptors, ALK4 and ALK5 (21). In previous studies, we presented genetic evidence supporting a role for both ACVR2 and ACVR2B in mediating MSTN signaling and regulating muscle mass in vivo. Specifically, we showed that mice expressing a truncated, dominant-negative form of ACVR2B in skeletal muscle (18) or carrying deletion mutations in Acvr2 and/or Acvr2b (13) have significantly increased muscle mass. One limitation of the latter study, however, was that we could not examine the consequence of complete loss of both receptors using the deletion alleles, as double homozygous mutants die early during embryogenesis (22). Moreover, the roles that the two type I receptors, ALK4 and ALK5, play in regulating MSTN and activin A signaling in muscle in vivo have not yet been documented using genetic approaches. Here, we present the results of studies in which we used floxed alleles for each of the type II and type I receptor genes in order to target these receptors alone and in combination in muscle fibers. We show that these receptors are functionally redundant and that signaling through each of these receptors contributes to the overall control of muscle mass.