Gary McCall - Academia.edu (original) (raw)

Papers by Gary McCall

Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology, 2000

Rhesus monkeys (Macaca mulatta) were trained to perform a foot lever pressing task for a food rew... more Rhesus monkeys (Macaca mulatta) were trained to perform a foot lever pressing task for a food reward. EMG activity was recorded from selected lower limb muscles of 2 animals before, during, and after a 14-day spaceflight and from 3 animals during a ground-based simulation of the flight. Integrated EMG activity was calculated for each muscle during the 20-min test. Comparisons were made between data recorded before any experimental manipulations and during flight or flight simulation. Spaceflight reduced soleus (Sol) activity to 25% of preflight levels, whereas it was reduced to 50% of control in the flight simulation. During flight, medial gastrocnemius (MG) activity was reduced to 25% of preflight activity, whereas the simulation group showed normal activity levels throughout all tests. The change in MG activity was apparent in the first inflight recording, suggesting that some effect of microgravity on MG activity was immediate.

Muscle & Nerve, Jul 1, 2008

Paired box (Pax) proteins 3 and 7 are key determinants for embryonic skeletal muscle development ... more Paired box (Pax) proteins 3 and 7 are key determinants for embryonic skeletal muscle development by initiating myogenic regulatory factor (MRF) gene expression. We show that Pax3 and 7 participate in adult skeletal muscle plasticity during the initial responses to chronic overload (≤7 days) and appear to coordinate MyoD expression, a member of the MRF family of genes. Pax3 and 7 mRNA were higher than control within 12 h after initiation of overload, preceded the increase in MyoD mRNA on day 1, and peaked on day 2. On days 3 and 7, Pax7 mRNA remained higher than control, suggesting that satellite cell self-renewal was occurring. Pax3 and 7 and MyoD protein levels were higher than control on days 2 and 3. These data indicate that Pax3 and 7 coordinate the recapitulation of developmental-like regulatory mechanisms in response to growth-inducing stimuli in adult skeletal muscle, presumably through activation of satellite cells.

International Journal of Exercise Science: Conference Proceedings, 2015

Aerobic exercise training promotes gene expression for physiological changes that must occur with... more Aerobic exercise training promotes gene expression for physiological changes that must occur with enhanced physical activity. Cessation of activity (detraining) theoretically reverses these adaptations, but it is unknown whether global gene expression profiles return to pre-training levels. PURPOSE: To compare gene expression profiles in the soleus muscle 24 hrs after an acute exercise bout in detrained, sedentary, and exercised rats. METHODS: Female Sprague-Dawley rats (n=8/group) were placed in one of three groups: voluntary exercise (EX) for 8 wks, sedentary (SED) for 8 wks, or a detraining model (DETR) in which animals ran voluntarily for 4 wks and were then sedentary for 4 wks. All animals were forced to run on a wheel for a total of 1 hour at 20 m/min and then killed 24 hrs later, when body and soleus muscle masses were recorded for each rat. Total mRNA extraction, conversion to cDNA, and microarray analyses were performed on the soleus muscle samples by Georgetown University to examine gene expression profiles. RESULTS: Body mass of EX rats was ~10% lower when compared to SED and DETR rats (p\u3c0.05); however, absolute soleus mass was \u3e10% higher in SED than in EX and DETR groups (p\u3c0.05). There was 9% lower relative soleus mass (mg muscle/ g body mass) in DETR vs. both EX and SED rats. Genes that exhibited a ≥2-fold difference in expression between groups from microarray analysis were identified, and using this criteria, we found differences in 289 known genes between SED and EX rats, 56 between SED and DETR rats, and 460 between EX and DETR rats (p\u3c0.05). CONCLUSION: Although the fewest differences in gene expression occurred between SED and DETR groups, microarray results showed that some training-induced adaptations persisted after 4 wks of detraining, suggesting that there is residual genetic benefit from previous exercising periods. Angiogenic gene expression will be confirmed using quantitative PCR, and capillary density will be quantified to further characterize physiological effects of detraining on skeletal muscle

International Journal of Exercise Science: Conference Proceedings, 2015

PURPOSE: Skeletal muscle is highly plastic and its properties can be modified under varying condi... more PURPOSE: Skeletal muscle is highly plastic and its properties can be modified under varying conditions. Functional overload (FO) of the mouse plantaris by removal of its major synergists results in marked hypertrophy and changes in the biochemical, contractile, and metabolic properties towards those of a “slow” muscle. How these changes are regulated remains largely unknown. Recent studies have shown that some neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), regulate the differentiation, survival and maintenance of neurons. In skeletal muscle, these neurotrophic factors are thought to be involved in the adaptation of the neuromuscular system to increased activity. Therefore, we investigated the effects of 1-wk FO with voluntary wheel running exercise (FO-EX) and without voluntary exercise on the expression of BDNF and NT-4/5 in the mouse plantaris muscle and its associated motoneurons. METHODS: Adult female C57BL/6J mice (~4 mos) were assigned to one of three groups: 1) CON; 2) FO, and; 3) FO-EX. Mice in the FO-EX group had free access to a running wheel. Immunohistochemical analyses were performed to assess BDNF protein expression in the plantaris-associated motoneurons, and RT-PCR experiments were performed to quantify BDNF and NT-4/5 mRNA levels in the plantaris muscle. RESULTS: BDNF protein expression in the plantaris-associated motoneurons was 9% and 12% greater (p\u3c0.05) in FO and FO-EX, respectively, compared with age-matched CON. BDNF mRNA expression was higher (p\u3c0.05) in the FO and FO-EX compared to the CON group. The increased expression of BDNF protein and mRNA in the FO-EX group could be due to the distance ran (~23.7 km) during the 1-wk period. In contrast, NT-4/5 mRNA levels in FO and FO-EX were similar to CON. CONCLUSIONS: FO and FO with activity preferentially increased BDNF expression in the plantaris muscle and its motoneurons. NT-4/5 did not respond to FO or FO with activity, implying that BDNF, not NT-4/5, regulates neuronal plasticity during skeletal muscle hypertrophy

Frontiers in Physiology, Oct 23, 2019

Aerobic physical activity triggers adaptations in skeletal muscle including a fast-toslow shift i... more Aerobic physical activity triggers adaptations in skeletal muscle including a fast-toslow shift in myosin heavy chain (MHC) isoforms, an enhanced capillary network, and mitochondrial biogenesis to meet increased demands placed upon this tissue. Although the magnitude of these responses appears to be dependent on muscle phenotype as well as training volume and/or intensity, the whole-muscle response to detraining remains mostly unexplored. Here, we hypothesized that the shifts toward slower MHC phentotype and the increased capillarity and mitochondrial oxidative markers induced with training would return toward sedentary (SED) control levels sooner in the fast plantaris than in the slow soleus muscle as a result of detraining. Soleus and plantaris muscles from 8-week (TR 8wk) voluntarily running adult female Sprague-Dawley rats were compared to muscles from SED and detrained rats (DETR) (4 weeks voluntary running followed by 4 weeks of reduced activity), which were subdivided into low-(DETR Lo) and high-running-distance (DETR Hi) groups. We show that maintaining the fast-to-slow MHC isoform shift required consistent aerobic training in the soleus and plantaris muscles: detraining clearly abolished any fast-to-slow gains in the plantaris, whereas the training volume in DETR Hi rats appeared to influence the MHC return to basal levels in the soleus. Total capillary number (per mm 2) in the plantaris increased in all groups compared to SED levels, but, in the soleus, this enhancement was observed only in the TR 8wk rats. Generally, increased mitochondrial markers for aerobicitiy were observed in TR 8wk plantaris, but not soleus, muscles. In a second experiment, we show that the muscle-specific adaptations were similar after 4 weeks of voluntary exercise (TR 4wk) as in 4 weeks (TR 8wk). Taken together, our findings suggest that the plantaris muscle is more sensitive to voluntary physical activity and detraining than the soleus muscle; these results also demonstrate that the soleus muscle requires a greater aerobic challenge (i.e., intensity, duration) to trigger phenotypic, angiogenic, or aerobic enzyme adaptations. Our findings generally suggest that muscular aerobic fitness to voluntary running, or its loss during detraining, manifests as changes occurring primarily within fast, rather than slow, muscle phenotypes.

Growth hormone & IGF research, Feb 1, 2020

To revisit a finding, first described in 1978, which documented existence of a pituitary growth f... more To revisit a finding, first described in 1978, which documented existence of a pituitary growth factor that escaped detection by immunoassay, but which was active in the established rat tibia GH bioassay. Methods: We present a narrative review of the evolution of growth hormone complexity, and its bio-detectability, from a historical perspective. Results: In humans under the age of 60, physical training (i.e. aerobic endurance and resistance training) are stressors which preferentially stimulate release of bioactive GH (bGH) into the blood. Neuroanatomical studies indicate a) that nerve fibers directly innervate the human anterior pituitary and b) that hind limb muscle afferents, in both humans and rats, also modulate plasma bGH. In the pituitary gland itself, molecular variants of GH, somatotroph heterogeneity and cell plasticity all appear to play a role in regulation of this growth factor. Conclusion: This review considers more recent findings on this often forgotten/neglected subject. Comparison testing of a) human plasma samples, b) sub-populations of separated rat pituitary somatotrophs or c) purified human pituitary peptides by GH bioassay vs immunoassay consistently yield conflicting results.

Canadian Journal of Applied Physiology-revue Canadienne De Physiologie Appliquee, Dec 1, 1998

This study aimed to determine the skeletal muscle fiber sample size required for a reliable, vali... more This study aimed to determine the skeletal muscle fiber sample size required for a reliable, valid representation of an individual's average fiber area and capillary contacts (CC) per fiber. Biopsies were obtained from the biceps brachii of 11 college-age, recreational resistance-trained men in conjunction with a study investigating how muscle morphology changed after 12 weeks of resistance training. The effect of additional measurements on the rolling cumulative means for fiber area and CC per fiber was evaluated using sequential estimation analysis. Results showed that group cumulative mean and standard deviation had stabilized by 50 fiber measurements per individual for type I and II fibers and CC per fiber. Significant correlations (.96-.99; p < .05) existed between the 50th and 95th/100th cumulative individual means. These results indicate that a typical skeletal muscle needle biopsy would be sufficient to characterize type I and II fiber areas and CC per fiber of an individual in most subject populations, although the required sample size for characterizing fiber subtypes might be different. Key words: muscle biopsy; sequential estimation analysis

Medicine and Science in Sports and Exercise, May 1, 2011

Medicine and Science in Sports and Exercise, May 1, 2002

Experimental Physiology, Sep 16, 2010

Skeletal muscle hypertrophy requires the co-ordinated expression of locally acting growth factors... more Skeletal muscle hypertrophy requires the co-ordinated expression of locally acting growth factors that promote myofibre growth and concurrent adaptive changes in the microvasculature. These studies tested the hypothesis that vascular endothelial growth factor (VEGF) and heparin-binding epidermal growth factor (HB-EGF) expression are upregulated during the early stages of compensatory muscle growth induced by chronic functional overload (FO). Bilateral FO of the plantaris and soleus muscles was induced for 3 or 7 days in the hindlimbs of adult female Sprague-Dawley rats (n = 5 per group) and compared with control (non-FO) rats. Relative muscle mass (in mg (kg body weight)(-1)) increased by 18 and 24% after 3 days and by 20 and 33% after 7 days in the plantaris and soleus muscles, respectively. No differences in HB-EGF mRNA or protein were observed in either muscle of FO rats relative to control muscles. The VEGF mRNA was similar in the soleus muscles of FO and control rats, whereas a significant elevation occurred at 3 and 7 days of FO in the plantaris muscle. However, VEGF protein expression after 3 days of FO exhibited a differential response; expression in the soleus muscle decreased 1.6-fold, whereas that in the plantaris muscle increased 1.8-fold compared with the control muscle. After 7 days of FO, VEGF protein remained elevated within the plantaris muscle, but returned to basal levels in the soleus. Robust basal HB-EGF and VEGF protein expression was consistently seen in control muscles. In all groups, immunohistochemistry for VEGF protein displayed a distinct striated expression pattern within myofibres, with considerably less labelling in extracellular spaces. Constitutive expression of HB-EGF and VEGF in control myofibres is consistent with housekeeping roles for these growth factors in skeletal muscle tissue. However, the specific patterns of VEGF expression in these muscles during FO may reflect the chronic changes in neural recruitment between muscles and the co-ordination of angiogenic and/or other hypertrophic responses.

Journal of Neurophysiology, May 1, 1999

Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus... more Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) and MG tendon force during quadrupedal stepping were studied in adult Rhesus before and after 14 days of either spaceflight (n ϭ 2) or flight simulation at 1G (n ϭ 3). Flight simulation involved duplication of the spaceflight conditions and experimental protocol in a 1G environment. Postflight, but not postsimulation, electromyographic (EMG) recordings revealed clonus-like activity in all muscles. Compared with preflight, the cycle period and burst durations of the primary extensors (Sol, MG, and VL) tended to decrease postflight. These decreases were associated with shorter steps. The flexor (TA) EMG burst duration postflight was similar to preflight, whereas the burst amplitude was elevated. Consequently, the Sol:TA and MG:TA EMG amplitude ratios were lower following flight, reflecting a ''flexor bias.'' Together, these alterations in mean EMG amplitudes reflect differential adaptations in motor-unit recruitment patterns of flexors and extensors as well as fast and slow motor pools. Shorter cycle period and burst durations persisted throughout the 20-day postflight testing period, whereas mean EMG returned to preflight levels by 17 days postflight. Compared with presimulation, the simulation group showed slight increases in the cycle period and burst durations of all muscles. Mean EMG amplitude decreased in the Sol, increased in the MG and VL, and was unchanged in the TA. Thus adaptations observed postsimulation were different from those observed postflight, indicating that there was a response unique to the microgravity environment, i.e., the modulations in the nervous system controlling locomotion cannot merely be attributed to restriction of movement but appear to be the result of changes in the interpretation of load-related proprioceptive feedback to the nervous system. Peak MG tendon force amplitudes were approximately two times greater post-compared with preflight or presimulation. Adaptations in tendon force and EMG amplitude ratios indicate that the nervous system undergoes a reorganization of the recruitment patterns biased toward an increased recruitment of fast versus slow motor units and flexor versus extensor muscles. Combined, these data indicate that some details of the control of motor pools during locomotion are dependent on the persistence of Earth's gravitational environment.

Medicine and Science in Sports and Exercise, May 1, 1995

ABSTRACT

Medicine and Science in Sports and Exercise, May 1, 1997

Journal of Applied Physiology, Jun 1, 2007

Early events in response to abrupt increases in activation and loading with muscle functional ove... more Early events in response to abrupt increases in activation and loading with muscle functional overload (FO) are associated with increased damage and inflammation. Heat shock protein 25 (HSP25) may protect against these stressors, and its expression can be regulated by muscle loading and activation. The purpose of this study was to investigate the responses of HSP25, phosphorylated HSP25 (pHSP25), and tumor necrosis factor-␣ (TNF-␣) during FO of the slow soleus and fast plantaris. We compared the HSP25 mRNA, HSP25 protein, pHSP25, and TNF-␣ responses in the soleus and plantaris after 0.5, 1, 2, 3, and 7 days of FO. HSP25 and pHSP25 were quantified in soluble and insoluble fractions. HSP25 mRNA increased immediately in both muscles and decreased with continued FO. However, HSP25 mRNA levels were consistently higher in the muscles of FO than control rats. In the soluble fraction, HSP25 increased in the plantaris after 2-7 days of FO with the greatest response at 3 and 7 days. The pHSP25 response to FO was greater in the plantaris than soleus at all points in the soluble fraction and at 0.5 days in the insoluble fraction. TNF-␣ levels in the plantaris, but not soleus, were higher than control at 0.5-2 days of FO. This may have contributed to the greater FO response in pHSP25 in the plantaris than soleus as TNF-␣ increased pHSP25 in C 2C12 myotubes. These results suggest that the initial responses of pHSP25 and TNF-␣ to mechanical stress and inflammation associated with FO are greater in a fast than slow extensor muscle.

The FASEB Journal, Apr 1, 2012

Medicine and Science in Sports and Exercise, May 1, 2004

Medicine and Science in Sports and Exercise, May 1, 1993

The Journal of Experimental Biology, Sep 15, 2001

The structural and functional properties of the neuromotor system of terrestrial animals have evo... more The structural and functional properties of the neuromotor system of terrestrial animals have evolved with a variety of design strategies that facilitate mobility in the gravitational environment of Earth. Experiments performed over the last century demonstrate that many of the details of the neural control of movement accommodate this gravitational environment by extensively using 'automatic' neural control strategies (Grillner, 1981). Not only are these neural strategies tightly linked to the structural features of the musculoskeletal system of a given species, but in effect these neuromotor features are linked to Earth's gravitational forces. It is often assumed that the degree to which humans depend on their automaticity of neural control to accommodate Earth's gravity (1 g), particularly during postural locomotor tasks, is far less than that of other terrestrial animals. In effect, we know little of how Earth's gravitational forces have impacted the evolution of neuromotor systems, including that of humans (

International Journal of Exercise Science: Conference Proceedings, 2015

Skeletal muscle extracellular matrix (ECM) is integral to various cellular behaviors. The gelatin... more Skeletal muscle extracellular matrix (ECM) is integral to various cellular behaviors. The gelatinases are a subfamily of zinc-dependent proteases called matrix metalloproteinases (MMPs) that degrade ECM proteins. MMP-9 primarily degrades type IV collagen, a component of the myofiber basal lamina. MMP-9 expression increases during remodeling conditions, such as load-inducing hypertrophy. PURPOSE: To investigate the hypertrophy response of the plantaris in C57 wildtype (WT) and MMP-9 knockout (KO) mice after 2 and 14 days of functional overload (FO) induced hypertrophy. METHODS: C57 wildtype (Harlan Labs) and KO (Jackson Labs) mice (age:10-14 weeks) underwent FO of the plantaris muscle using the bilateral synergist ablation model in which the medial and lateral gastrocnemii were surgically isolated and removed. After 2 or 14 days of FO, mice (n=6-11/group) were euthanized and the plantaris was removed bilaterally, weighed, frozen, and stored at -80°C. A two-way ANOVA (time x group) was used to compare mean relative plantaris weight (mg/g of body weight) among groups. Significance was set at p≤0.05. RESULTS: Mean ± SD relative plantaris weights were similar between WT and KO groups (main effect p=0.407; 0.068 ± 0.006 and 0.074 ± 0.015 mg/g at baseline, respectively). For both WT and KO groups, significant hypertrophy occurred (main effect p\u3c0.0001) after 2 day FO (0.091 ± 0.012 and 0.077 ± 0.005 mg/g, respectively) and continued through 14 day (0.110 ± 0.020 and 0.105 ± 0.027 mg/g, respectively). However, the hypertrophy response was similar among groups (interaction p=0.254). CONCLUSIONS: Inactivation of the MMP-9 gene did not affect the increase in relative muscle plantaris wet weight response to FO. To further understand the cellular hypertrophy response, ongoing analysis is focused on the quantification of the plantaris type IV collagen content by immunohistochemistry

Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology, 2000

Rhesus monkeys (Macaca mulatta) were trained to perform a foot lever pressing task for a food rew... more Rhesus monkeys (Macaca mulatta) were trained to perform a foot lever pressing task for a food reward. EMG activity was recorded from selected lower limb muscles of 2 animals before, during, and after a 14-day spaceflight and from 3 animals during a ground-based simulation of the flight. Integrated EMG activity was calculated for each muscle during the 20-min test. Comparisons were made between data recorded before any experimental manipulations and during flight or flight simulation. Spaceflight reduced soleus (Sol) activity to 25% of preflight levels, whereas it was reduced to 50% of control in the flight simulation. During flight, medial gastrocnemius (MG) activity was reduced to 25% of preflight activity, whereas the simulation group showed normal activity levels throughout all tests. The change in MG activity was apparent in the first inflight recording, suggesting that some effect of microgravity on MG activity was immediate.

Muscle & Nerve, Jul 1, 2008

Paired box (Pax) proteins 3 and 7 are key determinants for embryonic skeletal muscle development ... more Paired box (Pax) proteins 3 and 7 are key determinants for embryonic skeletal muscle development by initiating myogenic regulatory factor (MRF) gene expression. We show that Pax3 and 7 participate in adult skeletal muscle plasticity during the initial responses to chronic overload (≤7 days) and appear to coordinate MyoD expression, a member of the MRF family of genes. Pax3 and 7 mRNA were higher than control within 12 h after initiation of overload, preceded the increase in MyoD mRNA on day 1, and peaked on day 2. On days 3 and 7, Pax7 mRNA remained higher than control, suggesting that satellite cell self-renewal was occurring. Pax3 and 7 and MyoD protein levels were higher than control on days 2 and 3. These data indicate that Pax3 and 7 coordinate the recapitulation of developmental-like regulatory mechanisms in response to growth-inducing stimuli in adult skeletal muscle, presumably through activation of satellite cells.

International Journal of Exercise Science: Conference Proceedings, 2015

Aerobic exercise training promotes gene expression for physiological changes that must occur with... more Aerobic exercise training promotes gene expression for physiological changes that must occur with enhanced physical activity. Cessation of activity (detraining) theoretically reverses these adaptations, but it is unknown whether global gene expression profiles return to pre-training levels. PURPOSE: To compare gene expression profiles in the soleus muscle 24 hrs after an acute exercise bout in detrained, sedentary, and exercised rats. METHODS: Female Sprague-Dawley rats (n=8/group) were placed in one of three groups: voluntary exercise (EX) for 8 wks, sedentary (SED) for 8 wks, or a detraining model (DETR) in which animals ran voluntarily for 4 wks and were then sedentary for 4 wks. All animals were forced to run on a wheel for a total of 1 hour at 20 m/min and then killed 24 hrs later, when body and soleus muscle masses were recorded for each rat. Total mRNA extraction, conversion to cDNA, and microarray analyses were performed on the soleus muscle samples by Georgetown University to examine gene expression profiles. RESULTS: Body mass of EX rats was ~10% lower when compared to SED and DETR rats (p\u3c0.05); however, absolute soleus mass was \u3e10% higher in SED than in EX and DETR groups (p\u3c0.05). There was 9% lower relative soleus mass (mg muscle/ g body mass) in DETR vs. both EX and SED rats. Genes that exhibited a ≥2-fold difference in expression between groups from microarray analysis were identified, and using this criteria, we found differences in 289 known genes between SED and EX rats, 56 between SED and DETR rats, and 460 between EX and DETR rats (p\u3c0.05). CONCLUSION: Although the fewest differences in gene expression occurred between SED and DETR groups, microarray results showed that some training-induced adaptations persisted after 4 wks of detraining, suggesting that there is residual genetic benefit from previous exercising periods. Angiogenic gene expression will be confirmed using quantitative PCR, and capillary density will be quantified to further characterize physiological effects of detraining on skeletal muscle

International Journal of Exercise Science: Conference Proceedings, 2015

PURPOSE: Skeletal muscle is highly plastic and its properties can be modified under varying condi... more PURPOSE: Skeletal muscle is highly plastic and its properties can be modified under varying conditions. Functional overload (FO) of the mouse plantaris by removal of its major synergists results in marked hypertrophy and changes in the biochemical, contractile, and metabolic properties towards those of a “slow” muscle. How these changes are regulated remains largely unknown. Recent studies have shown that some neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), regulate the differentiation, survival and maintenance of neurons. In skeletal muscle, these neurotrophic factors are thought to be involved in the adaptation of the neuromuscular system to increased activity. Therefore, we investigated the effects of 1-wk FO with voluntary wheel running exercise (FO-EX) and without voluntary exercise on the expression of BDNF and NT-4/5 in the mouse plantaris muscle and its associated motoneurons. METHODS: Adult female C57BL/6J mice (~4 mos) were assigned to one of three groups: 1) CON; 2) FO, and; 3) FO-EX. Mice in the FO-EX group had free access to a running wheel. Immunohistochemical analyses were performed to assess BDNF protein expression in the plantaris-associated motoneurons, and RT-PCR experiments were performed to quantify BDNF and NT-4/5 mRNA levels in the plantaris muscle. RESULTS: BDNF protein expression in the plantaris-associated motoneurons was 9% and 12% greater (p\u3c0.05) in FO and FO-EX, respectively, compared with age-matched CON. BDNF mRNA expression was higher (p\u3c0.05) in the FO and FO-EX compared to the CON group. The increased expression of BDNF protein and mRNA in the FO-EX group could be due to the distance ran (~23.7 km) during the 1-wk period. In contrast, NT-4/5 mRNA levels in FO and FO-EX were similar to CON. CONCLUSIONS: FO and FO with activity preferentially increased BDNF expression in the plantaris muscle and its motoneurons. NT-4/5 did not respond to FO or FO with activity, implying that BDNF, not NT-4/5, regulates neuronal plasticity during skeletal muscle hypertrophy

Frontiers in Physiology, Oct 23, 2019

Aerobic physical activity triggers adaptations in skeletal muscle including a fast-toslow shift i... more Aerobic physical activity triggers adaptations in skeletal muscle including a fast-toslow shift in myosin heavy chain (MHC) isoforms, an enhanced capillary network, and mitochondrial biogenesis to meet increased demands placed upon this tissue. Although the magnitude of these responses appears to be dependent on muscle phenotype as well as training volume and/or intensity, the whole-muscle response to detraining remains mostly unexplored. Here, we hypothesized that the shifts toward slower MHC phentotype and the increased capillarity and mitochondrial oxidative markers induced with training would return toward sedentary (SED) control levels sooner in the fast plantaris than in the slow soleus muscle as a result of detraining. Soleus and plantaris muscles from 8-week (TR 8wk) voluntarily running adult female Sprague-Dawley rats were compared to muscles from SED and detrained rats (DETR) (4 weeks voluntary running followed by 4 weeks of reduced activity), which were subdivided into low-(DETR Lo) and high-running-distance (DETR Hi) groups. We show that maintaining the fast-to-slow MHC isoform shift required consistent aerobic training in the soleus and plantaris muscles: detraining clearly abolished any fast-to-slow gains in the plantaris, whereas the training volume in DETR Hi rats appeared to influence the MHC return to basal levels in the soleus. Total capillary number (per mm 2) in the plantaris increased in all groups compared to SED levels, but, in the soleus, this enhancement was observed only in the TR 8wk rats. Generally, increased mitochondrial markers for aerobicitiy were observed in TR 8wk plantaris, but not soleus, muscles. In a second experiment, we show that the muscle-specific adaptations were similar after 4 weeks of voluntary exercise (TR 4wk) as in 4 weeks (TR 8wk). Taken together, our findings suggest that the plantaris muscle is more sensitive to voluntary physical activity and detraining than the soleus muscle; these results also demonstrate that the soleus muscle requires a greater aerobic challenge (i.e., intensity, duration) to trigger phenotypic, angiogenic, or aerobic enzyme adaptations. Our findings generally suggest that muscular aerobic fitness to voluntary running, or its loss during detraining, manifests as changes occurring primarily within fast, rather than slow, muscle phenotypes.

Growth hormone & IGF research, Feb 1, 2020

To revisit a finding, first described in 1978, which documented existence of a pituitary growth f... more To revisit a finding, first described in 1978, which documented existence of a pituitary growth factor that escaped detection by immunoassay, but which was active in the established rat tibia GH bioassay. Methods: We present a narrative review of the evolution of growth hormone complexity, and its bio-detectability, from a historical perspective. Results: In humans under the age of 60, physical training (i.e. aerobic endurance and resistance training) are stressors which preferentially stimulate release of bioactive GH (bGH) into the blood. Neuroanatomical studies indicate a) that nerve fibers directly innervate the human anterior pituitary and b) that hind limb muscle afferents, in both humans and rats, also modulate plasma bGH. In the pituitary gland itself, molecular variants of GH, somatotroph heterogeneity and cell plasticity all appear to play a role in regulation of this growth factor. Conclusion: This review considers more recent findings on this often forgotten/neglected subject. Comparison testing of a) human plasma samples, b) sub-populations of separated rat pituitary somatotrophs or c) purified human pituitary peptides by GH bioassay vs immunoassay consistently yield conflicting results.

Canadian Journal of Applied Physiology-revue Canadienne De Physiologie Appliquee, Dec 1, 1998

This study aimed to determine the skeletal muscle fiber sample size required for a reliable, vali... more This study aimed to determine the skeletal muscle fiber sample size required for a reliable, valid representation of an individual's average fiber area and capillary contacts (CC) per fiber. Biopsies were obtained from the biceps brachii of 11 college-age, recreational resistance-trained men in conjunction with a study investigating how muscle morphology changed after 12 weeks of resistance training. The effect of additional measurements on the rolling cumulative means for fiber area and CC per fiber was evaluated using sequential estimation analysis. Results showed that group cumulative mean and standard deviation had stabilized by 50 fiber measurements per individual for type I and II fibers and CC per fiber. Significant correlations (.96-.99; p < .05) existed between the 50th and 95th/100th cumulative individual means. These results indicate that a typical skeletal muscle needle biopsy would be sufficient to characterize type I and II fiber areas and CC per fiber of an individual in most subject populations, although the required sample size for characterizing fiber subtypes might be different. Key words: muscle biopsy; sequential estimation analysis

Medicine and Science in Sports and Exercise, May 1, 2011

Medicine and Science in Sports and Exercise, May 1, 2002

Experimental Physiology, Sep 16, 2010

Skeletal muscle hypertrophy requires the co-ordinated expression of locally acting growth factors... more Skeletal muscle hypertrophy requires the co-ordinated expression of locally acting growth factors that promote myofibre growth and concurrent adaptive changes in the microvasculature. These studies tested the hypothesis that vascular endothelial growth factor (VEGF) and heparin-binding epidermal growth factor (HB-EGF) expression are upregulated during the early stages of compensatory muscle growth induced by chronic functional overload (FO). Bilateral FO of the plantaris and soleus muscles was induced for 3 or 7 days in the hindlimbs of adult female Sprague-Dawley rats (n = 5 per group) and compared with control (non-FO) rats. Relative muscle mass (in mg (kg body weight)(-1)) increased by 18 and 24% after 3 days and by 20 and 33% after 7 days in the plantaris and soleus muscles, respectively. No differences in HB-EGF mRNA or protein were observed in either muscle of FO rats relative to control muscles. The VEGF mRNA was similar in the soleus muscles of FO and control rats, whereas a significant elevation occurred at 3 and 7 days of FO in the plantaris muscle. However, VEGF protein expression after 3 days of FO exhibited a differential response; expression in the soleus muscle decreased 1.6-fold, whereas that in the plantaris muscle increased 1.8-fold compared with the control muscle. After 7 days of FO, VEGF protein remained elevated within the plantaris muscle, but returned to basal levels in the soleus. Robust basal HB-EGF and VEGF protein expression was consistently seen in control muscles. In all groups, immunohistochemistry for VEGF protein displayed a distinct striated expression pattern within myofibres, with considerably less labelling in extracellular spaces. Constitutive expression of HB-EGF and VEGF in control myofibres is consistent with housekeeping roles for these growth factors in skeletal muscle tissue. However, the specific patterns of VEGF expression in these muscles during FO may reflect the chronic changes in neural recruitment between muscles and the co-ordination of angiogenic and/or other hypertrophic responses.

Journal of Neurophysiology, May 1, 1999

Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus... more Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) and MG tendon force during quadrupedal stepping were studied in adult Rhesus before and after 14 days of either spaceflight (n ϭ 2) or flight simulation at 1G (n ϭ 3). Flight simulation involved duplication of the spaceflight conditions and experimental protocol in a 1G environment. Postflight, but not postsimulation, electromyographic (EMG) recordings revealed clonus-like activity in all muscles. Compared with preflight, the cycle period and burst durations of the primary extensors (Sol, MG, and VL) tended to decrease postflight. These decreases were associated with shorter steps. The flexor (TA) EMG burst duration postflight was similar to preflight, whereas the burst amplitude was elevated. Consequently, the Sol:TA and MG:TA EMG amplitude ratios were lower following flight, reflecting a ''flexor bias.'' Together, these alterations in mean EMG amplitudes reflect differential adaptations in motor-unit recruitment patterns of flexors and extensors as well as fast and slow motor pools. Shorter cycle period and burst durations persisted throughout the 20-day postflight testing period, whereas mean EMG returned to preflight levels by 17 days postflight. Compared with presimulation, the simulation group showed slight increases in the cycle period and burst durations of all muscles. Mean EMG amplitude decreased in the Sol, increased in the MG and VL, and was unchanged in the TA. Thus adaptations observed postsimulation were different from those observed postflight, indicating that there was a response unique to the microgravity environment, i.e., the modulations in the nervous system controlling locomotion cannot merely be attributed to restriction of movement but appear to be the result of changes in the interpretation of load-related proprioceptive feedback to the nervous system. Peak MG tendon force amplitudes were approximately two times greater post-compared with preflight or presimulation. Adaptations in tendon force and EMG amplitude ratios indicate that the nervous system undergoes a reorganization of the recruitment patterns biased toward an increased recruitment of fast versus slow motor units and flexor versus extensor muscles. Combined, these data indicate that some details of the control of motor pools during locomotion are dependent on the persistence of Earth's gravitational environment.

Medicine and Science in Sports and Exercise, May 1, 1995

ABSTRACT

Medicine and Science in Sports and Exercise, May 1, 1997

Journal of Applied Physiology, Jun 1, 2007

Early events in response to abrupt increases in activation and loading with muscle functional ove... more Early events in response to abrupt increases in activation and loading with muscle functional overload (FO) are associated with increased damage and inflammation. Heat shock protein 25 (HSP25) may protect against these stressors, and its expression can be regulated by muscle loading and activation. The purpose of this study was to investigate the responses of HSP25, phosphorylated HSP25 (pHSP25), and tumor necrosis factor-␣ (TNF-␣) during FO of the slow soleus and fast plantaris. We compared the HSP25 mRNA, HSP25 protein, pHSP25, and TNF-␣ responses in the soleus and plantaris after 0.5, 1, 2, 3, and 7 days of FO. HSP25 and pHSP25 were quantified in soluble and insoluble fractions. HSP25 mRNA increased immediately in both muscles and decreased with continued FO. However, HSP25 mRNA levels were consistently higher in the muscles of FO than control rats. In the soluble fraction, HSP25 increased in the plantaris after 2-7 days of FO with the greatest response at 3 and 7 days. The pHSP25 response to FO was greater in the plantaris than soleus at all points in the soluble fraction and at 0.5 days in the insoluble fraction. TNF-␣ levels in the plantaris, but not soleus, were higher than control at 0.5-2 days of FO. This may have contributed to the greater FO response in pHSP25 in the plantaris than soleus as TNF-␣ increased pHSP25 in C 2C12 myotubes. These results suggest that the initial responses of pHSP25 and TNF-␣ to mechanical stress and inflammation associated with FO are greater in a fast than slow extensor muscle.

The FASEB Journal, Apr 1, 2012

Medicine and Science in Sports and Exercise, May 1, 2004

Medicine and Science in Sports and Exercise, May 1, 1993

The Journal of Experimental Biology, Sep 15, 2001

The structural and functional properties of the neuromotor system of terrestrial animals have evo... more The structural and functional properties of the neuromotor system of terrestrial animals have evolved with a variety of design strategies that facilitate mobility in the gravitational environment of Earth. Experiments performed over the last century demonstrate that many of the details of the neural control of movement accommodate this gravitational environment by extensively using 'automatic' neural control strategies (Grillner, 1981). Not only are these neural strategies tightly linked to the structural features of the musculoskeletal system of a given species, but in effect these neuromotor features are linked to Earth's gravitational forces. It is often assumed that the degree to which humans depend on their automaticity of neural control to accommodate Earth's gravity (1 g), particularly during postural locomotor tasks, is far less than that of other terrestrial animals. In effect, we know little of how Earth's gravitational forces have impacted the evolution of neuromotor systems, including that of humans (

International Journal of Exercise Science: Conference Proceedings, 2015

Skeletal muscle extracellular matrix (ECM) is integral to various cellular behaviors. The gelatin... more Skeletal muscle extracellular matrix (ECM) is integral to various cellular behaviors. The gelatinases are a subfamily of zinc-dependent proteases called matrix metalloproteinases (MMPs) that degrade ECM proteins. MMP-9 primarily degrades type IV collagen, a component of the myofiber basal lamina. MMP-9 expression increases during remodeling conditions, such as load-inducing hypertrophy. PURPOSE: To investigate the hypertrophy response of the plantaris in C57 wildtype (WT) and MMP-9 knockout (KO) mice after 2 and 14 days of functional overload (FO) induced hypertrophy. METHODS: C57 wildtype (Harlan Labs) and KO (Jackson Labs) mice (age:10-14 weeks) underwent FO of the plantaris muscle using the bilateral synergist ablation model in which the medial and lateral gastrocnemii were surgically isolated and removed. After 2 or 14 days of FO, mice (n=6-11/group) were euthanized and the plantaris was removed bilaterally, weighed, frozen, and stored at -80°C. A two-way ANOVA (time x group) was used to compare mean relative plantaris weight (mg/g of body weight) among groups. Significance was set at p≤0.05. RESULTS: Mean ± SD relative plantaris weights were similar between WT and KO groups (main effect p=0.407; 0.068 ± 0.006 and 0.074 ± 0.015 mg/g at baseline, respectively). For both WT and KO groups, significant hypertrophy occurred (main effect p\u3c0.0001) after 2 day FO (0.091 ± 0.012 and 0.077 ± 0.005 mg/g, respectively) and continued through 14 day (0.110 ± 0.020 and 0.105 ± 0.027 mg/g, respectively). However, the hypertrophy response was similar among groups (interaction p=0.254). CONCLUSIONS: Inactivation of the MMP-9 gene did not affect the increase in relative muscle plantaris wet weight response to FO. To further understand the cellular hypertrophy response, ongoing analysis is focused on the quantification of the plantaris type IV collagen content by immunohistochemistry