Time course of gene expression changes after muscle contraction in spinal cord injured rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE37476 | GEO | 2013/03/30
SECONDARY ACCESSION(S): PRJNA162663
REPOSITORIES: GEO
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Project description:Purpose: The goal of this study was to determine the gene expression changes that occur over 7 days in parralyzed muscle in response to isometric contraction elicited by electrical stimulation initiated 4 months after spinal cord injury and to compare such changes to those observed in a normal muscle subjected to overload. Methods: Electrical stimulation of the soleus and plantaris muscle was stimulated in female rats with complete transection of the spinal cord at the interspace between the 9th and 10th thoracic vertebrae. Stimulation was begun 16 weeks after spinal cord transection and produced near-isometric contraction of soleus, plantaris and tibialis anterior. Muscle was analyzed at 1, 2 and 7 days after starting exercise with electrical stimulation. To provide a baseline reference for gene expression at 16 weeks after spinal cord injury, muscle was also analysed from an additional group of spinal cord transected animals. One additional group of animals with a sham-spinal cord injury was included to provide information about gene expression in neurologically intact animals of similar age. In parallel studies, rats underwent bilateral gastrocnemius ablation to overload soleus and plantaris, or a sham ablation as a control. Muscle was analyzed at 1, 3 and 7 days after gastrocnemius ablation or sham-ablation. Gene expression was determined using Affymetrix Rat Exon microarrays. For each group of animals, microarray analysis was performed for soleus muscle for each of 3 separate animals, using one array per animal. Control sammples for the spinal cord injured groups included a group of animals with a Sham-spinal cord injury, and a group of spinal cord injured animals that did not get electrical stimulation. The comparator for determining fold-change expression values was the spinal cord injured group that did not receive electrical stimulation. For each day after gastrocnemius ablation, a control was included that received all procedures needed for this ablation except cutting the distal insertion of the gastrocnemius into the Achilles tendon to control for effects of the surgery on gene expression.
2013-03-30 | E-GEOD-37476 | biostudies-arrayexpress
Project description:Fast skeletal myosin binding protein-C (fMyBP-C) is one of three MyBP-C paralogs and is predominantly expressed in fast skeletal muscle. Mutations in the gene that encodes fMyBP-C, MYBPC2, is associated with distal arthrogryposis, while fMyBP-C protein is reduced in diseased muscle. However, the functional and structural roles of fMyBP-C in skeletal muscle remain unclear. To address this gap, we generated a homozygous fMyBP-C knockout mouse (C2-/-) and characterized it, both in vivo and in vitro. Ablation of fMyBP-C was benign in terms of muscle weight, fiber type, cross-sectional area, and sarcomere ultrastructure. However, grip strength and plantar-flexor muscle strength were significantly decreased in C2-/- compared to WT. Peak isometric tetanic force (Po) and isotonic speed of contraction were significantly reduced in isolated extensor digitorum longus (EDL) from C2-/- mice. In EDL muscles of C2-/- mice, small-angle X-ray diffraction revealed significant increase in equatorial intensity ratio (I1.1/I1.0) during contraction, indicating a greater degree of myosin head shift towards actin while MLL4 layer-line intensity was decreased at rest, indicating less ordered myosin heads at rest. Interfilament lattice spacing was also significantly increased in C2-/- EDL muscle compared to WT. Consistent with these findings, we observed a significant reduction of steady-state isometric force during Ca2+ activations, myofilament calcium sensitivity, sinusoidal stiffness in skinned EDL muscle fibers from C2-/- mice. Finally, C2-/- muscles displayed disruption of inflammatory and regenerative genes and increased muscle damage upon mechanical overload. Together, our data suggest that fMyBP-C is essential for maximal speed and force of contraction, sarcomere integrity, and calcium sensitivity in fast twitch muscle.
2020-11-30 | GSE160827 | GEO
Project description:Study to examine the effect of a demanding 15 minute whole hindlimb isometric contraction protocol in vivo on changes in gene expression, 4 hours post-contraction. Keywords = skeletal muscle Keywords = isometric contractions
2010-06-06 | E-GEOD-1679 | biostudies-arrayexpress
Project description:Study to examine the effect of a demanding 15 minute whole hindlimb isometric contraction protocol in vivo on changes in gene expression, 4 hours post-contraction. Keywords = skeletal muscle Keywords = isometric contractions Keywords: parallel sample
2004-08-17 | GSE1679 | GEO
Project description:Mice were subjected to 50 eccentric contractions (EC) or 50 isometric contractions (IC) using a non-invasive model, and then sacrificed 48 hours later. RNA from the tibialis anterior of 4 animals were pooled and then split into two groups for hybridization onto two separate Affymetrix MGU74Av2 chips. Control samples were contralateral to the exercised legs, and were only subjected to enough contractions to measure isometric torque. Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result in muscle injury and, eventually, muscle strengthening and prevention of further injury. Although the mechanical basis of eccentric contraction-induced injury has been studied in detail, muscle's biological response is less well characterized. This study presents the development of a minimally-invasive model of EC injury in the mouse, follows the time course of torque recovery after an injurious bout of ECs, and uses Affymetrix microarrays to compare the gene expression profile 48 hours after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by about 55% immediately after the exercise bout, and recovered to initial levels 7 days later. 36 known genes were upregulated after ECs compared to contralateral and isometrically stimulated muscles, including five muscle specific genes: muscle LIM protein (MLP), Muscle Ankyrin Repeat Proteins (MARP 1 and 2; also known as cardiac ankyrin repeat protein and Arpp/Ankrd2, respectively), Xin, and Myosin Binding Protein H. The time courses of MLP and MARP expression after the injury bout (determined by quantitative real-time polymerase chain reaction) indicate that these genes are rapidly induced, reaching a peak expression level of 6-11 times contralateral values 12-24 hours after the EC bout and returning to baseline within 72 hours. Very little gene induction was seen after either isometric activation or passive stretch, indicating that the MLP and MARP genes may play an important and specific role in the biological response of muscle to EC-induced injury. Keywords = mouse tibialis anterior eccentric contraction muscle
2007-11-06 | E-GEOD-435 | biostudies-arrayexpress
Project description:Electrical stimulation can augment or modify neuronal function and can have therapeutic benefits for certain neurological disorders. There is evidence that enhancing spinal excitability with either epidural or transcutaneous stimulation can restore some volitional motor output after spinal cord injury (SCI). Lumbosacral epidural stimulation temporarily improves locomotor and autonomic function in both rodents and humans with SCI. When combined with overground locomotor training enabled by a weight-supporting device, epidural electrical stimulation (EES) promotes extensive reorganization of residual neural pathways that improves locomotion after stopping stimulation. However, the exact mechanism underlying the reconstruction of spinal cord neural circuits with electrical stimulation is not yet known. Thus, we developed a epidural electrical and muscle stimulation(EEMS) system at the interface of the spinal cord and muscle to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. Using methods of motor function evaluation, neural circuit tracing and neural signal recording, we discovered a unique stimulus frequency of 10-20 Hz under EEMS conditions that was required for structural and functional reconstruction of spinal sensorimotor circuits. Single-cell transcriptome analysis of EEMS activated motoneurons characterized molecular networks involved in spinal sensorimotor circuit reconstruction. This study provides insights into neural signal decoding during spinal sensorimotor circuit reconstruction, and indicates a technological approach for the clinical treatment of SCI.
2023-12-05 | GSE243038 | GEO
Project description:Spinal cord injury (SCI) causes severe bone loss and disrupts connections between higher centers in the central nervous system (CNS) and bone. Muscle contraction elicited by functional electrical stimulation (FES) partially protects against loss of bone but cellular and molecular events by which this occurs are unknown. Here, using a rat model, we characterized effects of 7 days of contraction-induced loading of tibia and fibula due to FES when begun 16 weeks after SCI. SCI reduced tibial and femoral BMD by 12-17% and promoted bone resorption, as indicated by increased serum CTX; SCI-related changes in CTX were reversed by FES. In cultures of bone marrow cell-derived cells, SCI increased the number of osteoclasts and mRNA levels of the several osteoclast differentiation markers; these changes were significantly reversed by FES. The number of osteoblasts was also reduced by SCI as was the ratio of OPG/RANKL mRNAs therein; the unfavorable change in OPG/RANKL ratio was partially reversed by FES. cDNA microarray analysis revealed that alterations in genes involved in signaling through Wnt, FSH/LH, PTH and calcineurin/NFAT pathways may be linked to the favorable action of FES on SCI-induced bone resorption. In particular, SCI increased levels of the Wnt inhibitors DKK1, sFRP2 and SOST in osteoblasts, These effects were completely or partially reversed by FES. Our results demonstrate an anti-bone resorptive activity of acute FES in bone loss after SCI and suggest potential underlying mechanisms, among them involving increased Wnt signaling to cause more favorable ratios of OPG and RANKL for the inhibition of osteoclastogenesis. The present study indicates that the effects of bone reloading on SCI- related bone remodeling occurred independently of the effects of higher CNS centers on bone.
2012-06-28 | GSE30301 | GEO
Project description:Background: Niemann-Pick disease type A (NPDA), a disease caused by mutations in acid sphingomyelinase (ASM), involves severe neurodegeneration and early death. Intracellular lipid accumulation and plasma membrane alterations are implicated in the pathology. ASM is also linked to the mechanism of plasma membrane repair, so we investigated the impact of ASM deficiency in skeletal muscle, a tissue that undergoes frequent cycles of injury and repair in vivo. Methods: Utilizing the NPDA/B mouse model ASM−/− and wild type (WT) littermates, we performed excitation- contraction coupling/Ca2+ mobilization and sarcolemma injury/repair assays with isolated flexor digitorum brevis fibers, proteomic analyses with quadriceps femoris, flexor digitorum brevis, and tibialis posterior muscle and in vivo tests of the contractile force (maximal isometric torque) of the quadriceps femoris muscle before and after eccentric contraction-induced muscle injury. Results: ASM−/− flexor digitorum brevis fibers showed impaired excitation-contraction coupling compared to WT, a defect expressed as reduced tetanic [Ca2+]i in response to electrical stimulation and early failure in sustaining [Ca2+]i during repeated tetanic contractions. When injured mechanically by needle passage, ASM−/− flexor digitorum brevis fibers showed susceptibility to injury similar to WT, but a reduced ability to reseal the sarcolemma. Proteomic analyses revealed changes in a small group of skeletal muscle proteins as a consequence of ASM deficiency, with downregulation of calsequestrin occurring in the three different muscles analyzed. In vivo, the loss in maximal isometric torque of WT quadriceps femoris was similar immediately after and 2 min after injury. The loss in ASM−/− mice immediately after injury was similar to WT, but was markedly larger at 2 min after injury. Conclusions: Skeletal muscle fibers from ASM−/− mice have an impairment in intracellular Ca2+ handling that results in reduced Ca2+ mobilization and a more rapid decline in peak Ca2+ transients during repeated contraction-relaxation cycles. Isolated fibers show reduced ability to repair damage to the sarcolemma, and this is associated with an exaggerated deficit in force during recovery from an in vivo eccentric contraction- induced muscle injury. Our findings uncover the possibility that skeletal muscle functional defects may play a role in the pathology of NPDA/B disease.
2023-06-28 | PXD019356 | Pride
Project description:Spinal cord injury (SCI) causes severe bone loss and disrupts connections between higher centers in the central nervous system (CNS) and bone. Muscle contraction elicited by functional electrical stimulation (FES) partially protects against loss of bone but cellular and molecular events by which this occurs are unknown. Here, using a rat model, we characterized effects of 7 days of contraction-induced loading of tibia and fibula due to FES when begun 16 weeks after SCI. SCI reduced tibial and femoral BMD by 12-17% and promoted bone resorption, as indicated by increased serum CTX; SCI-related changes in CTX were reversed by FES. In cultures of bone marrow cell-derived cells, SCI increased the number of osteoclasts and mRNA levels of the several osteoclast differentiation markers; these changes were significantly reversed by FES. The number of osteoblasts was also reduced by SCI as was the ratio of OPG/RANKL mRNAs therein; the unfavorable change in OPG/RANKL ratio was partially reversed by FES. cDNA microarray analysis revealed that alterations in genes involved in signaling through Wnt, FSH/LH, PTH and calcineurin/NFAT pathways may be linked to the favorable action of FES on SCI-induced bone resorption. In particular, SCI increased levels of the Wnt inhibitors DKK1, sFRP2 and SOST in osteoblasts, These effects were completely or partially reversed by FES. Our results demonstrate an anti-bone resorptive activity of acute FES in bone loss after SCI and suggest potential underlying mechanisms, among them involving increased Wnt signaling to cause more favorable ratios of OPG and RANKL for the inhibition of osteoclastogenesis. The present study indicates that the effects of bone reloading on SCI- related bone remodeling occurred independently of the effects of higher CNS centers on bone. Implantation of the FES microstimulators was performed 14 weeks after SCI. The FES was begun during the 16th week following spinal cord transection. Stimulation was provided for 60 minutes on each training day and consisted of brief periods of contraction (2 seconds) at 40 Hz at 1.5 V with longer periods of rest (18 seconds). Animals received FES on 7 consecutive days; collection of blood and tissues occurred at day at after initiating FES, as described below. The SCI-Sham FES animals received the implant surgery and gastrocnemius ablation during the 14th week after the spinal cord transection, but did not have a stimulator unit inserted; samples were collected from these animals at week 17. To provide age-matched non-SCI controls, additional animals underwent a sham-SCI surgery identical to that for the SCI animals, except that the spinal cord was not transected. Tissues were collected from these animals at 12-14 weeks after surgery. Of note, at this age, animals were sexually mature and their growth minimal. To collect blood and tissues, animals were anesthetized by inhalation of isofluorane followed by removal of the soleus and plantaris muscles after careful dissection and collection of blood by ventricular puncture and aspiration. Animals were euthanized by aortic transaction and tibia and femur were removed as a single piece, leaving the knee joint intact, and placed in a-MEM for isolation of bone marrow cells. Muscles were weighed; weights are expressed after being normalized to body weight before SCI or sham-SCI surgeries to control for individual variations in size.
2012-06-27 | E-GEOD-30301 | biostudies-arrayexpress
Project description:Polycystic ovary syndrome (PCOS) is characterised by a hormonal imbalance affecting the reproductive and metabolic health of reproductive-aged women. Exercise is often recommended as a first-line therapy for women with PCOS to help improve their overall health however, women with PCOS are resistant to the metabolic benefits of exercise training. Here, we aimed to gain insight into the mechanisms responsible for such resistance to exercise in PCOS. We employed an in vitro approach with electrical pulse stimulation (EPS) of cultured skeletal muscle cells to explore whether muscle cells from women with PCOS have an altered gene expression signature in response to muscle contraction. Following EPS, 4,719 genes were differentially expressed (FDR < 0.05) in myotubes from women with PCOS compared to only 173 in healthy control women. Both groups included genes involved in skeletal muscle contraction. We also determined the effect of two transforming growth factor-beta ligands that are elevated in plasma of women with PCOS, the transforming growth factor beta-1 (TGFβ1) and the anti-müllerian hormone (AMH), alone and on the EPS-induced response. While AMH (30 ng/ml) had no effect, TGFβ1 (5 ng/ml) induced the expression of extracellular matrix genes and impaired the exercise-like gene expression signature in myotubes from women with and without PCOS in response to EPS by interfering with key processes related to muscle contraction, calcium transport and actin filament. Collectively, our findings suggest that while the fundamental gene expression responses of skeletal muscle to contraction is intact in PCOS, elevated circulating factors like TGFβ1 may be responsible for the impaired adaptation to exercise intervention in women with PCOS.
2022-10-12 | GSE199225 | GEO