bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of aging and treadmill exercise on cognitive function and the expression of BDNF in the hippocampus
Authors: Maejima Hiroshi , Kanemura Naohiko , Kokubun Takanori , Murata Kenji , Takayanagi Kiyomi 
Published: November 2023

Neurotrophins play a crucial role in neuroplasticity, neurogenesis, and neuroprotection in the central nervous system. Aerobic exercise is known to increase the expression of brain‐derived neurotrophic factor (BDNF) in the hippocampus. The objective of this study was to investigate the effects of aging and moderate exercise on cognitive function and the expression of BDNF in the hippocampus using senescence‐accelerated mouse P1 (SAMP1) and its age‐matched control mouse (SAMR1).13‐month‐old SAMR1 and SAMP1 mice were randomly distributed to four groups based on two factors comprising accelerated aging (SAMR1 versus SAMP1) and exercise (sedentary versus exercise), i.e. SAMR1 sedentary group (R1‐Sed), SAMR1 exercise group (R1‐Ex), SAMP1 csedentary group (P1‐Con) and SAMP1 exercise group (P1‐Ex). The exercised mice performed moderate treadmill exercise (12 m/min, 60 min) five times a week for four weeks. After four week intervention, the novel‐object recognition test was performed to evaluate recognition memory. The expression of mRNA and protein abundance of neurotrophins of BDNF in the hippocampus was assayed using Real time PCR and ELISA. A two‐way analysis of variance (ANOVA) was performed for each analysis to investigate the effects of accelerated aging (R1 versus P1) and exercise (sedentary versus exercise), as well as two‐factor interaction. All study procedures were approved by the ethics committee for animal research of Saitama Prefectural University in Japan and conducted according to the guidelines of the committee.A two‐way ANOVA showed a significant factorial effect of exercise and no significant interaction in the score of the novel‐object recognition test, the expression of mRNA and protein abundance of BDNF, demonstrating that the exercise improved the recognition memory and up‐regulated the expression of BDNF similarly in SAMR1 and SAMP1. This study elucidated the beneficial effects of the moderate exercise on the expression of BDNF in SAMP1 as well as in SAMR1, suggesting that moderate exercise could contribute to protect the degeneration of cognitive function in the elderly through the up‐regulation of BDNF expression in the hippocampus.Support or Funding InformationThis work was supported by JSPS KAKENHI Grant 21500471.
The Effect of Exercise Pattern on Insulin Responses in Healthy, Young Males
Authors: Castleberry Todd , Ramirez Joel , Deemer Sarah E , Irvine Christopher , Rouwtt De'Andrea , Oldham Michael , Ben‐Ezra Vic 
Published: November 2023

BACKGROUNDIt is often reported that a single bout of exercise lowers insulin responses 12–24 hours post exercise. It is not known if alternate or consecutive days of exercise have an additive effect on insulin responses. Our hypothesis is that both alternate and consecutive days of exercise will improve insulin responses/glucose control more than a single bout of exercise.PURPOSEThe purpose of this study was to examine the effect of exercise pattern on post‐exercise insulin and glucose responses to a glucose challenge.METHODSEleven healthy adult male participants (n=11, mean ± SD, 28.6 ± 7.9 yrs; BMI: 25.7 ± 2.8 kg/m2, VO2max; 38.7 ± 4.7 ml/kg/min; fasting plasma glucose: 4.85 mmol/l; fasting plasma insulin: 8.4 μU/ml) completed three submaximal exercise trials of walking on a treadmill for 60 minutes at ~70% of VO2max. The trials consisted of: 3 consecutive exercise days (3CON), 3 alternate exercise days (3ALT), a single bout of exercise (SB), and a no exercise control (R). In the morning, 12–14 hours after the last bout of exercise or R, participants completed a 75g oral glucose tolerance test and blood was collected at 0, 30, 60, 90, 120, and 150 minutes for the measurement of glucose, insulin, and C‐peptide. Glucose was analyzed using enzyme electrode technology (YSI 2900) and insulin and C‐peptide were measured via ELISA. A one‐way repeated measures ANOVA with a Bonferroni post hoc was used for statistical analysis. Diet logs were kept throughout each trial to ensure consistency for all participants.RESULTSCalculated integrated area under the curve (iAUC) for glucose and C‐peptide was not different between the 4 trials. Insulin iAUC was significantly decreased 33.9% for 3CON compared to R (p=0.006). Insulin iAUC decreased for SB (8.4%) and 3ALT (24.1%) compared to R, however these values did not reach statistical significance.CONCLUSIONThree consecutive days of walking at ~70% VO2max improved insulin response to a 75g glucose load compared to no exercise. Interestingly, a single bout of exercise and three alternate days of exercise did not significantly improve insulin responses compared to no exercise. It is possible, that for healthy, young males, the response to a single bout of exercise, or exercise bouts separated by more than 24 hours may not be enough stimulus to improve insulin responses.
Post‐effects of walking intensity on cardiovascular function and autonomic regulation in patients with intermittent claudication
Authors: Chehuen Marcel , Lima Aluisio H. , Silva Natan Daniel , Costa Luiz Augusto Riani , Miyasato Roberto Sanches , Wolosker Nelson , Forjaz Cláudia 
Published: November 2023

IntroductionPatients with intermittent claudication (IC) exhibit limited walking capacity and often present cardiovascular alterations, such as high blood pressure (BP), endothelial dysfunction and cardiac autonomic dysfunction. Walking training is recommended to these individuals to improve walking capacity, and some authors suggest that maximal walking (until maximal pain) may be more effective than submaximal walking. An acute submaximal walking session has been shown to promote post‐exercise hypotension, while the effect of maximal walking on this parameter is unknown.ObjectiveTo compare the acute post‐effect of submaximal and maximal walking on cardiovascular function and autonomic regulation in patients with IC.MethodsThirty patients with IC (66 ± 11 years) underwent two experimental session: one submaximal (15 bouts of 2 min of walking at the heart rate (HR) of pain threshold interpolated by 2 min of upright rest) and one maximal (walking at 2 mph with 2% increase in grade every 2 min until maximal leg pain). HR (ECG), BP (auscultatory), rate pressure product (RPP), resting and after reactive hyperemia blood flow (BF) (plethysmography), and low (LF) and high (HF) frequency components of HR variability were measured before and 30 minutes after the walking protocols. A 2‐way ANOVA for repeated measures was used (P<0.05).ResultsIn comparison with the pre‐exercise values, systolic and mean BP decreased and diastolic BP did not change after the submaximal walking, while these BPs increased after the maximal walking (−7±7 vs. +5±7, −3±3 vs. +5±5 and 0±3 vs. +5±4 mmHg, respectively). HR increased similarly after the submaximal and the maximal walking (+3±4 vs. +3±6 bpm, respectively), while RPP did not change after the submaximal, but increased after the maximal walking (−158±645 vs. +752±791 mmHg*bpm). Resting forearm and leg BF (+0.24±0.22 vs. +0.27±0.22 and +0.78±0.79 vs. +0.66±1.03 ml.100ml tissue−1.min−1, respectively) as well as forearm BF after reactive hyperemia (+1.7±4.5 vs. +2.2±3.9 ml.100ml tissue−1.min−1, respectively) increased similarly after the submaximal and maximal walking, while leg BF after reactive hyperemia did not change after any session (0.0±3.5 vs. −0.1±2.6 ml.100ml tissue−1.min−1, respectively). LF increased, HF decreased and LF/HF increased similarly after the submaximal and the maximal walking (+8±21 vs. +9±20 nu; −9±17 vs. −10±20 nu and 0.2±0.4 vs. 0.2±0.5, respectively).ConclusionIn patients with IC, an acute submaximal but not maximal walking session promotes post‐exercise hypotension; while cardiac work (RPP) increases only after maximal walking. On the other hand, BF, vasodilation, HR and cardiac sympathovagal modulation increases after both maximal and submaximal walking.Support or Funding InformationFinancial support: CNPQ e FAPESP.
Angiotensin‐II Rapidly Decreases MiR‐23a and MiR‐182 in Muscle Cells
Authors: Pautz Carina M , Pinson Catherine L , Jackson Kelli , Burke Marcus A , Kelly Ellen M , Hudson Matthew B 
Published: November 2023

Numerous chronic pathological conditions are associated with elevated circulating levels of Angiotensin II (Ang II). A substantial amount of previous research has focused on the effects of elevated Ang II on the heart and vasculature. However, skeletal muscle atrophy occurs during several chronic conditions associated with elevated circulating Ang II, including cardiovascular, renal disease and certain cancers. Thus, more recent research has begun to investigate the potential role of elevated Ang II in the progression of skeletal muscle atrophy. Several microRNAs, including miR‐23a and miR‐182, participate in skeletal muscle atrophy by regulating the level of key atrophy‐inducing proteins. Previously, we demonstrated that the intracellular levels of these microRNAs are reduced in in C2C12 myotubes within 1–2 hours following the administration of glucocorticoids, and this rapid change in key microRNAs may be one of the initial steps in the muscle atrophy process. Therefore, the purpose of the present study was to investigate if Ang II administration to C2C12 myotubes activates muscle atrophy signaling potentially through altered intracellular levels of key microRNAs. Administration of Ang II (1μM) to myotubes resulted in a significant decrease in both miR‐23a (~38%) and miR‐182 (~31%) at 24 hours. However, miR‐23a was significantly decreased (~28%) within half an hour while miR‐182 was not significantly decreased (~42%) until three hrs. Both miR‐23a and miR‐182 returned to baseline levels 48 hours following Ang II administration. Further, 24 hours following Ang II administration MuRF‐1 was significantly increased (~21%) and while Atrogin‐1 was significantly increased at 48 hrs (75These findings demonstrate that Ang II decreases the level of microRNAs known to participate in muscle atrophy, and this decrease occurs prior to the elevation of Atrogin‐1 and MuRF1. This data suggests a possible miRNA‐mediated regulation of Ang II‐induced skeletal muscle atrophy.Support or Funding InformationSupported by NIH GM087239
Dual Specificity Phosphatase and Pro Isomerase Domain Containing 1 (Dupd1) is Upregulated During Neurogenic Skeletal Muscle Atrophy and is Differentially Expressed in MuRF1‐null Mice
Authors: West Rita , Waddell David 
Published: November 2023

Skeletal muscle atrophy is caused by a decrease in muscle size and strength and results from a range of physiological conditions, including denervation, immobilization, corticosteroid exposure and aging. Dual Specificity Phosphatase and Pro Isomerase Domain Containing 1 (Dupd1) has been identified as a novel atrophy‐induced gene in skeletal muscle and has been found to be differentially regulated in wild‐type mice compared to Muscle RING Finger 1 (MuRF1) knockout mice in response to denervation. Muscle RING Finger 1 (MuRF1), an E3 ubiquitin ligase, has previously been shown to be upregulated under almost all conditions of skeletal muscle wasting, is an important marker for skeletal muscle atrophy, and is believed to play an important role in targeting proteins for degradation. However, preliminary data described in this study provides evidence that MuRF1 may also act as a transcriptional modulator of atrophy‐induced gene activity, including the regulation of Dupd1. Microarray data revealed that Dupd1 expression is significantly induced at 3 days and 14 days post‐denervation in wild‐type mice, while Dupd1 expression is dramatically blunted in MuRF1‐null mice at both 3 days and 14 days post‐denervation. The Dupd1 gene codes for a dual specificity phosphatase protein that can dephosphorylate tyrosine and serine/threonine phosphorylated amino acid residues on substrate proteins. Dupd1, thought to be an atypical dual specificity phosphatase (DUSP), is believed to be a mitogen‐activated protein kinase phosphatase (MKP) and is likely capable of dephosphorylating mitogen‐activated protein kinases (MAPK). The results presented here in combination with additional research into the transcriptional regulation and function of Dupd1 in skeletal muscle helps contribute new insight into the molecular genetic mechanisms of muscle atrophy and could provide a more complete understanding of how MuRF1 may transcriptionally regulate neurogenic atrophy‐induced gene expression during muscle wasting.Support or Funding InformationThe work was support by University of North Florida Transformational Learning Opportunity grants to D.W.
Inflammatory Signaling Regulation of Eccentric Contraction–induced Muscle Protein Synthesis in Cachectic Skeletal Muscle
Authors: Hardee Justin P , Gao Song , VanderVeen Brandon N , Fix Dennis K , Carson James A 
Published: November 2023

Eccentric muscle contractions (ECC) induce growth that is associated with increased protein synthesis regulated by mTORC1. While disrupted muscle protein turnover occurs during cancer cachexia, cachectic muscle's capacity to respond to ECC is not well understood. Repeated ECC bouts during the progression of cachexia can attenuate muscle mass loss, reduce muscle inflammatory signaling, and decrease AMPK activation. However, cachectic muscle's ability to induce protein synthesis through mTORC1 has not examined. Therefore, we examined if cancer‐induced muscle inflammatory signaling involving STAT3 and NFkB could disrupt ECC‐induced protein synthesis. Either pharmacological (PDTC, a STAT3/NFkB inhibitor) or non‐pharmacological (ECC training) treatments were used to alter muscle inflammatory signaling. mTORC1 signaling and protein synthesis was examined 3h after a single bout of ECC in C57BL/6 (B6; N=9) and cachectic ApcMin/+ (MIN; N=9; 16% BW loss) mice. A subset of MIN mice (N=6; 17% BW loss) also received a single PDTC injection 24h prior to acute muscle contraction. The acute response after ECC training (8 bouts over 2 weeks) in C57BL/6 (N=8) and MIN mice (N=9; 15% BW loss) was also examined. In all experiments the left tibialis anterior (TA) performed ECC while the right TA served as intra‐animal control. Cachexia decreased TA muscle mass, mTORC1 signaling, and protein synthesis when compared to B6 controls. While the ECC induction of p70S6K(T389) phosphorylation was not attenuated by cachexia, the protein synthesis induction by ECC remained suppressed compared to B6 controls. Inhibition of STAT3/NFkB signaling increased basal muscle protein synthesis in MIN mice, which was further enhanced by ECC. The acute ECC induction of muscle protein synthesis was not altered by training. These data demonstrate that basal muscle protein synthesis in cachectic muscle is regulated by muscle inflammatory signaling. However, cachectic muscle inflammatory signaling does not alter the ECC induction of mTORC1 signaling and muscle protein synthesis.Support or Funding InformationSupported by NCI R01‐CA121249 (JAC) and an ACSM Foundation Research Grant (JPH).
Satellite Cell Depletion Impacts Skeletal Muscle Recovery Following a Burn Injury
Authors: Fry Christopher S , Cambias Lauren A , Prasai Anesh , Wang Ye , El Ayadi Amina , Herndon David , Suman Oscar , Finnerty Celeste 
Published: November 2023

Severe burn results in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we previously showed concurrent activation and apoptosis of muscle satellite cells (SC) following a burn injury in pediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7‐DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5‐ethynyl‐2′‐deoxyuridine (EdU) to determine satellite cell proliferation, activation and fusion. Juvenile SC‐wild type and SC‐depleted mice (8 weeks of age) were randomized to sham or burn injury, consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hind‐limb and dorsal muscles were studied at 7, 14 and 21 days post‐burn. SC‐depleted mice had >93% fewer SC than SC‐wild type (P<0.05). Burn injury induced robust atrophy in muscles located both proximal and distal to the injury site (~30% decrease in fiber cross‐sectional area, P<0.05). Additionally, burn injury induced skeletal muscle regeneration, satellite cell proliferation and fusion. Depletion of satellite cells impaired post‐burn muscle recovery. These findings support an integral role for satellite cells in the etiology of lean tissue recovery following a severe burn injury.Support or Funding InformationThis project was supported by a pilot grant from the UTMB Department of Surgery and NIH grants P30 AG024832, P50 GM60338, R01 GM56687, R01 HD049471 and Shriners grants SHC 80480 and SHC 80500.
Differential Expression of the Angiotensin II Type 1 Receptor Amongst Various Skeletal Muscle Types
Authors: Hinkley J. Matthew , Morton Aaron B , Smuder Ashley J , Powers Scott K 
Published: November 2023

Prolonged periods of skeletal muscle inactivity (e.g. limb immobilization and mechanical ventilation) results in muscle fiber atrophy. However, the rate of disuse muscle atrophy differs between skeletal muscles, as fiber atrophy occurs rapidly in the diaphragm during mechanical ventilation in comparison to limb muscles exposed to prolonged periods of inactivity. The mechanism(s) that explain the differential response between these muscles remains unknown. The angiotensin II type 1 (AT1) receptor, while widely recognized for its role on blood pressure and fluid balance regulation, has recently been implicated as a potential regulator of skeletal muscle mass; however, presence of the receptor in skeletal muscle is controversial. To determine if the diaphragm and limb skeletal muscles exhibit differential expression of the AT1 receptor, samples from the diaphragm and limb muscles (i.e., soleus, extensor digitorum longus, and plantaris) were obtained from female Sprague‐Dawley rats. Presence of the AT1 receptor was assessed by immunoblot analysis and in vitro binding of the fluorescent‐labeled ligand angiotensin II (Ang II). Interestingly, both protein content and in vitro Ang II binding revealed a significantly higher presence of the AT1 receptor in the diaphragm in comparison to all limb skeletal muscles investigated. To further elucidate the potential role of the AT1 receptor in mediating skeletal muscle atrophy, we examined alterations in mRNA expression of the AT1 receptor under disuse conditions of the diaphragm (prolonged mechanical ventilation) and the soleus muscle (limb immobilization). Surprisingly, although both the diaphragm and soleus muscle experienced atrophy, these muscles revealed a differential response in AT1 receptor expression. Specifically, mRNA expression of the AT1 receptor increased (~1.9‐fold) in the diaphragm following mechanical ventilation, whereas limb immobilization resulted in a decrease (~0.6‐fold) in receptor expression in the soleus muscle. Together, these results indicate that skeletal muscle contains a functional AT1 receptor that is differentially regulated between the diaphragm and limb skeletal muscles in control conditions and during prolonged periods of muscle inactivity. These data are consistent with the notion that the AT1 receptor may be a contributing factor in the differential atrophic response of skeletal muscle following prolonged durations of muscle inactivity.Support or Funding InformationNIH AR064189 and HD043730
Effects of Moderate Iron Loading on Skeletal Muscle Function and Oxidative Injury
Authors: Liang Chen , Benson Marisa , DeRuisseau Keith C 
Published: November 2023

Skeletal muscle iron overload is known to increase oxidative injury and impair contractile function. However, the impact of a moderate, physiologically‐relevant degree of muscle iron loading on contractile function has not been investigated. Thus, this study examined effects of moderate iron loading on skeletal muscle function and oxidative injury induced by subcutaneous injections of iron dextran. Young‐adult male mice received injections of iron dextran (4 mg iron/200μL) or vehicle (dextrose) 5 days per week for a period of two weeks (n=10/group). One day following the last injection the soleus muscle was harvested to assess levels of non‐heme iron (NHI), oxidative injury, and contractile properties. Liver and soleus NHI was approximately 4‐fold greater in mice that received injections of iron compared to vehicle (p<0.05). No difference in animal body mass or soleus muscle mass was observed (p>0.05). Maximal specific tension of the soleus was lower among iron loaded animals (22.4±0.1 N/cm2) compared to controls (26.2±0.9 N/cm2; p<0.05). However, soleus lipid peroxidation (4‐hydroxynoneal) and protein oxidation (protein carbonyls) levels were not different between the groups (p>0.05). In summary, a moderate elevation in muscle iron reduced contractile function by a mechanism that does not appear to involve oxidative stress. Additional experiments are being conducted to reveal a possible mechanism behind the iron‐mediated reduction in muscle force production.Support or Funding InformationSupported by the Syracuse University SOE
Curcumin Supplementation Effects on Aging Skeletal Muscle
Authors: Receno Candace N , Liang Chen , Korol Donna L , DeRuisseau Keith C 
Published: November 2023

The decline in muscle mass and function with age, termed sarcopenia, leads to an inability to perform normal daily activities and a subsequent deterioration in quality of life. An increase in oxidative stress that results from an inability to adequately quench reactive oxygen species has been cited as an important mechanism of sarcopenia. Curcumin, the active ingredient in the spice turmeric, has garnered much attention due to its antioxidative properties. Although curcumin's antioxidant properties may also make it beneficial to sarcopenia, this theory has not been tested. Thus, this study examined the effects of curcumin supplementation on muscle force characteristics in aging rats. Fourteen thirty‐two‐month‐old, male F344xBN rats were provided purified diets (AIN‐93M) for four months. One group received the diet ad libitum (CON, n=5), a second group consumed the same diet which also contained 0.2% curcumin (CUR, n=4), and a third, pair fed (PAIR, n=4) group was included that received the purified diet in an amount equal to the food consumed by CUR animals. Following the supplementation period, the plantaris was assessed for in vivo twitch and tetanic force generation measurements. Body mass, muscle mass, and contractile characteristics were analyzed using independent sample t‐tests. Data are expressed as mean±SEM. CUR and PAIR animals had a lower dietary intake compared to the CON group, however, animal body mass did not differ between groups (p>0.05). Muscle mass (g) was significantly lower in the PAIR group (0.190±.019, p<0.05), while CUR and CON muscle mass was similar (0.285±0.016 and 0.306±0.014, respectively). Peak twitch and peak tetanic tension were not significantly different between groups (p>.05). However, normalized peak tetanic tension (N/g) was 30% higher in the CUR group compared to the PAIR group (CUR=77.52±9.881, PAIR=59.6±2.556). Studies are on‐going to increase sample size numbers and continue testing the effects of curcumin on muscle function parameters. Preliminary findings suggest that dietary curcumin may attenuate the declines in muscle mass incurred by a reduced food intake among pair fed, aging rats. We are also investigating the mechanisms by which curcumin may elicit these changes, which include measurements of antioxidant expression and activity, and oxidative stress.Support or Funding InformationSupported by the NIH, National Institute on Aging, Grant #1R36AG050734 ‐ 01 (CNR).