Jessica Pingel

Acute exercise improves motor memory: exploring potential biomarkers.

We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memory and skill acquisition. Thirty-two healthy young male subjects were randomly allocated into either an exercise or control group. Following either an intense bout of cycling or rest subjects practiced a visuomotor tracking task. Motor skill acquisition was assessed during practice and retention 1 h, 24 h and 7 days after practice. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epinephrine, norepinephrine, dopamine and lactate were analyzed at baseline, immediately after exercise or rest and during motor practice. The exercise group showed significantly better skill retention 24h and 7 days after acquisition. The concentration of all blood compounds increased significantly immediately after exercise and remained significantly elevated for 15 min following exercise except for BDNF and VEGF. Higher concentrations of norepinephrine and lactate immediately after exercise were associated with better acquisition. Higher concentrations of BDNF correlated with better retention 1 h and 7 days after practice. Similarly, higher concentrations of norepinephrine were associated with better retention 7 days after practice whereas lactate correlated with better retention 1h as well as 24 h and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory.

Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

Women are at greater risk than men for certain kinds of diseases and injuries, which may at least partly be caused by sex hormonal differences. We aimed to test the influence of estradiol in vivo on collagen synthesis in tendon, bone, and muscle. Two groups of young, healthy women similar in age, body composition, and exercise-training status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n = 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low concentrations of estradiol and progesterone (control, n = 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [(13)C]proline followed by biopsies from the patellar tendon and vastus lateralis in both legs. Simultaneously, microdialysis catheters were inserted in vastus lateralis and in front of the patellar tendon for measurement of insulin-like growth factor I (IGF-I) and its binding proteins. Serum NH(2)-terminal propeptide of type I collagen (PINP) and urine COOH-terminal telopeptides of type-I collagen (CTX-I) were measured as markers for bone synthesis and breakdown, respectively. Tendon FSR and PINP were lower in OC compared with control. An increase in muscle collagen FSR postexercise was only observed in control (P < 0.05). Furthermore, the results indicate a lower bioavailability of IGF-I in OC. In conclusion, synthetic female sex hormones administered as OC had an inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I.

Local biochemical and morphological differences in human Achilles tendinopathy: a case control study

BackgroundThe incidence of Achilles tendinopathy is high and underlying etiology as well as biochemical and morphological pathology associated with the disease is largely unknown. The aim of the present study was to describe biochemical and morphological differences in chronic Achilles tendinopathy. The expressions of growth factors, inflammatory mediators and tendon morphology were determined in both chronically diseased and healthy tendon parts.MethodsThirty Achilles tendinopathy patients were randomized to an expression-study (n = 16) or a structural-study (n = 14). Biopsies from two areas in the Achilles tendon were taken and structural parameters: fibril density, fibril size, volume fraction of cells and the nucleus/cytoplasm ratio of cells were determined. Further gene expressions of various genes were analyzed.ResultsSignificantly smaller collagen fibrils and a higher volume fraction of cells were observed in the tendinopathic region of the tendon. Markers for collagen and its synthesis collagen 1, collagen 3, fibronectin, tenascin-c, transforming growth factor-β fibromodulin, and markers of collagen breakdown matrix metalloproteinase-2, matrix metalloproteinase-9 and metallopeptidase inhibitor-2 were significantly increased in the tendinopathic region. No altered expressions of markers for fibrillogenesis, inflammation or wound healing were observed.ConclusionThe present study indicates that an increased expression of factors stimulating the turnover of connective tissue is present in the diseased part of tendinopathic tendons, associated with an increased number of cells in the injured area as well as an increased number of smaller and thinner fibrils in the diseased tendon region. As no fibrillogenesis, inflammation or wound healing could be detected, the present data supports the notion that tendinopathy is an ongoing degenerative process.Trial registrationCurrent Controlled Trials ISRCTN20896880Background The incidence of Achilles tendinopathy is high and underlying etiology as well as biochemical and morphological pathology associated with the disease is largely unknown. The aim of the present study was to describe biochemical and morphological differences in chronic Achilles tendinopathy. The expressions of growth factors, inflammatory mediators and tendon morphology were determined in both chronically diseased and healthy tendon parts.

3-D ultrastructure and collagen composition of healthy and overloaded human tendon: evidence of tenocyte and matrix buckling

Achilles tendinopathies display focal tissue thickening with pain and ultrasonography changes. Whilst complete rupture might be expected to induce changes in tissue organization and protein composition, little is known about the consequences of non‐rupture‐associated tendinopathies, especially with regards to changes in the content of collagen type I and III (the major collagens in tendon), and changes in tendon fibroblast (tenocyte) shape and organization of the extracellular matrix (ECM). To gain new insights, we took biopsies from the tendinopathic region and flanking healthy region of Achilles tendons of six individuals with clinically diagnosed tendinopathy who had no evidence of cholesterol, uric acid and amyloid accumulation. Biochemical analyses of collagen III/I ratio were performed on all six individuals, and electron microscope analysis using transmission electron microscopy and serial block face‐scanning electron microscopy were made on two individuals. In the tendinopathic regions, compared with the flanking healthy tissue, we observed: (i) an increase in the ratio of collagen III : I proteins; (ii) buckling of the collagen fascicles in the ECM; (iii) buckling of tenocytes and their nuclei; and (iv) an increase in the ratio of small‐diameter : large‐diameter collagen fibrils. In summary, load‐induced non‐rupture tendinopathy in humans is associated with localized biochemical changes, a shift from large‐ to small‐diameter fibrils, buckling of the tendon ECM, and buckling of the cells and their nuclei.

Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women

Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women. Patches with estrogen (Evorel) were placed on the skin above the patellar tendons and compared with no patch (control period). On day 2 all subjects performed one-legged exercise, and thereafter the exercised leg (EX leg) was compared with the nonexercised leg (Rest leg). Microdialysis catheters were placed in front of the patellar tendons and in the vastus lateralis muscle of both legs at days 3 and 5. The collected dialysate was analyzed for procollagen type I NH(2)-terminal propeptide (PINP), insulin-like growth factor I (IGF-I), and interleukin-6 (IL-6). Neither loading (Rest leg vs. EX leg) nor treatment (control vs. ERT) influenced peritendinous PINP, whereas combined exercise and ERT enhanced muscle PINP after 72 h (interaction between loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise.

Increased mast cell numbers in a calcaneal tendon overuse model

Tendinopathy is often discovered late because the initial development of tendon pathology is asymptomatic. The aim of this study was to examine the potential role of mast cell involvement in early tendinopathy using a high‐intensity uphill running (HIUR) exercise model. Twenty‐four male Wistar rats were divided in two groups: running group (n = 12); sedentary control group (n = 12). The running‐group was exposed to the HIUR exercise protocol for 7 weeks. The calcaneal tendons of both hind limbs were dissected. The right tendon was used for histologic analysis using Bonar score, immunohistochemistry, and second harmonic generation microscopy (SHGM). The left tendon was used for quantitative polymerase chain reaction (qPCR) analysis. An increased tendon cell density in the runners were observed compared to the controls (P = 0.05). Further, the intensity of immunostaining of protein kinase B, P = 0.03; 2.75 ± 0.54 vs 1.17 ± 0.53, was increased in the runners. The Bonar score (P = 0.05), and the number of mast cells (P = 0.02) were significantly higher in the runners compared to the controls. Furthermore, SHGM showed focal collagen disorganization in the runners, and reduced collagen density (P = 0.03). IL‐3 mRNA levels were correlated with mast cell number in sedentary animals. The qPCR analysis showed no significant differences between the groups in the other analyzed targets. The current study demonstrates that 7‐week HIUR causes structural changes in the calcaneal tendon, and further that these changes are associated with an increased mast cell density.

The Microvascular Volume of the Achilles Tendon Is Increased in Patients With Tendinopathy at Rest and After a 1-Hour Treadmill Run

Background: Achilles tendinopathy (AT) is initiated asymptomatically and is therefore often discovered at a very late stage. Purpose: To elucidate whether the microvascular volume (MV) of the Achilles tendon is elevated in patients with AT compared with healthy controls during pre-exercise rest, after acute exercise, and 24 hours after exercise. Additionally, this study investigated the muscle activation pattern of the gastrocnemius muscle and the relative elasticity of the Achilles tendon during a 1-hour treadmill run in healthy patients and in patients with AT. Study Design: Controlled laboratory study. Methods: Real-time harmonic contrast-enhanced ultrasound (CEU) measurements of the MV of the Achilles tendon were taken in 18 volunteers (9 patients with AT, 9 healthy controls). The CEU analyses were conducted before exercise, immediately after a 1-hour treadmill run, and 24 hours after exercise. Surface electromyography (EMG) signals of the gastrocnemius were recorded continuously during the 1-hour treadmill run. Results: In both the controls and the patients with AT, the MV of the Achilles tendon was increased after exercise as compared with before exercise (P < .005). Additionally, the MV signal was significantly larger in the patients with AT before, immediately after, and 24 hours after the running exercise compared with values in healthy controls (P < .0001). The muscle activation pattern differed in patients with AT compared with controls in that controls had increased EMG amplitudes at the end of the 1-hour treadmill run in the medial and lateral gastrocnemius (P < .0001). Moreover, patients with AT had approximately 15% less elastic Achilles tendons at the beginning of the 1-hour treadmill run, a condition that did not change because of exercise. Conclusion: Acute exercise increases the MV of the Achilles tendon in healthy patients and patients with AT in a similar manner. However, patients with AT have a significantly larger MV at all time points compared with healthy patients, supporting the hypothesis that microvascular changes may be involved in the pathogenesis of tendinopathy. Clinical Relevance: This study underlines that tendon flexibility is altered in patients with AT and that CEU is a promising tool to establish the early diagnosis of this condition.

The acute effects of exercise on the microvascular volume of Achilles tendons in healthy young subjects.

Real‐time harmonic contrast‐enhanced ultrasound (CEU) is used in several diseases to visualize the microvascularization in various tissues, due to its high sensitivity.

Short-term acetaminophen consumption enhances the exercise-induced increase in Achilles peritendinous IL-6 in humans

Through an unknown mechanism, the cyclooxygenase inhibitor and antipyretic acetaminophen (APAP) alters tendon mechanical properties in humans when consumed during exercise. Interleukin-6 (IL-6) is produced by tendon during exercise and is a potent stimulator of collagen synthesis. In nontendon tissue, IL-6 is upregulated in the presence of cyclooxygenase inhibitors and may contribute to alterations in extracellular matrix turnover, possibly due to inhibition of prostaglandin E2 (PGE2). We evaluated the effects of APAP on IL-6 and PGE2 in human Achilles peritendinous tissue after 1 h of treadmill exercise. Subjects were randomly assigned to a placebo (n = 8, 26 ± 1 yr) or APAP (n = 8, 25 ± 1 yr) group. Each subject completed a nonexercise and exercise experiment consisting of 6 h of microdialysis. Drug (APAP, 1,000 mg) or placebo was administered in a double-blind manner during both experiments. PGE2 and IL-6 were determined via enzyme immunoassay and APAP via high-performance liquid chromatography. In subjects given APAP, peritendinous APAP levels increased to 4.08 ± 0.65 μg/ml (P < 0.05). PGE2 did not increase with exercise in either group (P > 0.05), nor was PGE2 significantly reduced in the APAP group. IL-6 levels increased with exercise in both groups (P < 0.05), but this increase was greater in the APAP group (P < 0.05). Our findings suggest that APAP enhances tendon IL-6 production after exercise. Peak levels of APAP obtained in the peritendinous space were twofold lower than values reported in plasma or skeletal muscle. These findings provide insight into the effects of APAP on tendon and provide novel information on the kinetics of APAP in tendon tissue after oral APAP consumption.

Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy.

Background Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager’s fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager’s fat pad and its surrounding structures during movement of the ankle, suggesting that Kager’s fat pad may stabilize and protect the mechanical function of the ankle joint. Aim The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager’s fat pad. Methods A biopsy was taken from Kager’s fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism. Results Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls. Conclusion Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager’s fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager’s fat pad of Achilles tendinopathy patients.