Impaired exercise capacity, but unaltered mitochondrial respiration in skeletal or cardiac muscle of mice lacking cellular prion protein

Nico, Patrícia Barreto Costa; Lobão-Soares, Bruno; Landemberger, Michele Christine; Marques, Wilson; Tasca, Carla I.; Mello, Carlos Fernando; Walz, Roger; Carlotti, Carlos Gilberto; Brentani, Ricardo R.; Sakamoto, Américo Ceiki; Bianchin, Marino Muxfeldt

doi:10.1016/j.neulet.2005.06.033

Cited by 17 publications

(15 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to wild-type controls, Nico et al (30) found that PrP-deficient animals have lower swimming capacities and less locomotor activity after bouts of forced exercise. In a separate study (31), the authors challenged mice with forced swimming under different loads and found that PrP-deficient animals could swim for less time. These data suggest PrP is essential for normal exercise performance but do not identify the organ(s) impaired by PrP deficiency (e.g., skeletal muscle, nervous system, cardiovascular, or pulmonary tissue).…”

Section: Introductionmentioning

confidence: 99%

Prion Protein Expression and Functional Importance in Skeletal Muscle

Smith

Moylan

Hardin

et al. 2011

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Skeletal muscle expresses prion protein (PrP) that buffers oxidant activity in neurons. Aims: We hypothesize that PrP deficiency would increase oxidant activity in skeletal muscle and alter redox-sensitive functions, including contraction and glucose uptake. We used real-time polymerase chain reaction and Western blot analysis to measure PrP mRNA and protein in human diaphragm, five murine muscles, and muscle-derived C2C12 cells.Effects of PrP deficiency were tested by comparing PrP-deficient mice versus wild-type mice and morpholinoknockdown versus vehicle-treated myotubes. Oxidant activity (dichlorofluorescin oxidation) and specific force were measured in murine diaphragm fiber bundles. Results: PrP content differs among mouse muscles (gastrocnemius > extensor digitorum longus, EDL > tibialis anterior, TA; soleus > diaphragm) as does glycosylation (di-, mono-, nonglycosylated; gastrocnemius, EDL, TA = 60%, 30%, 10%; soleus, 30%, 40%, 30%; diaphragm, 30%, 30%, 40%). PrP is predominantly di-glycosylated in human diaphragm. PrP deficiency decreases body weight (15%) and EDL mass (9%); increases cytosolic oxidant activity (fiber bundles, 36%; C2C12 myotubes, 7%); and depresses specific force (12%) in adult (8-12 mos) but not adolescent (2 mos) mice. Innovation: This study is the first to directly assess a role of prion protein in skeletal muscle function. Conclusions: PrP content varies among murine skeletal muscles and is essential for maintaining normal redox homeostasis, muscle size, and contractile function in adult animals. Antioxid. Redox Signal. 15, 2465-2475.

show abstract

Section: Introductionmentioning

confidence: 99%

Prion Protein Expression and Functional Importance in Skeletal Muscle

Smith

Moylan

Hardin

et al. 2011

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…One such tissue is skeletal muscle, which has been shown to express PrP C at significant levels (43,46) and has been found to upregulate PrP C levels under stress conditions (71). On the other hand, ablation of the PrP gene has been shown to directly affect skeletal muscles, for example, by enhancing oxidative damage (30) or by diminishing tolerance for physical exercise (51). Skeletal muscles have also been associated with prion pathology, as evidenced by the accumulation of PrP Sc (or PrP Sc -like forms) in the muscles of TSEaffected humans and animals (2,3,6,21,53,67) and by transgenic-mouse models of some inherited TSEs (16).…”

mentioning

confidence: 99%

Cellular Prion Protein Promotes Regeneration of Adult Muscle Tissue

Stella¹,

Massimino

Sandri

et al. 2010

Molecular and Cellular Biology

View full text Add to dashboard Cite

It is now well established that the conversion of the cellular prion protein, PrP C , into its anomalous conformer, PrP Sc , is central to the onset of prion disease. However, both the mechanism of prion-related neurodegeneration and the physiologic role of PrP C are still unknown. The use of animal and cell models has suggested a number of putative functions for the protein, including cell signaling, adhesion, proliferation, and differentiation. Given that skeletal muscles express significant amounts of PrP C and have been related to PrP C pathophysiology, in the present study, we used skeletal muscles to analyze whether the protein plays a role in adult morphogenesis. We employed an in vivo paradigm that allowed us to compare the regeneration of acutely damaged hind-limb tibialis anterior muscles of mice expressing, or not expressing, PrP C . Using morphometric and biochemical parameters, we provide compelling evidence that the absence of PrP C significantly slows the regeneration process compared to wild-type muscles by attenuating the stress-activated p38 pathway, and the consequent exit from the cell cycle, of myogenic precursor cells. Demonstrating the specificity of this finding, restoring PrP C expression completely rescued the muscle phenotype evidenced in the absence of PrP C .

show abstract

“…Additionally, Zurich 1 mice have been shown to have impaired swimming capacity, the magnitude of which increased as the task difficulty increased [93].…”

Section: Behavior Assays Have Been Used To Validate Prion Knockout Micementioning

confidence: 99%

Neurobehavioral Testing in Prion Disease Studies

Seelig¹,

Benneyworth²,

Bryant³

2017

Prion - An Overview

View full text Add to dashboard Cite

The prion diseases are neurodegenerative diseases characterized by progressive neurocognitive decline and terminal dementia. In this review, we will discuss the role of neurobehavioral testing in mammalian prion disease model systems, including (1) a review of the clinical phenotype of the major prion diseases in natural disease, (2) an evidence-based summary of the benefits and shortcomings of commonly used behavioral assays, and (3) a review of the neurobehavioral testing in rodent prion models. Based upon this review, and in light of the established importance of model systems in studies of prion pathogenesis and the proven role of behavioral testing in nonprion disease neurodegenerative diseases, it is vital that prion researchers consider the clinical consequences of prion infection so as to maximize the impact of their work.

show abstract

Impaired exercise capacity, but unaltered mitochondrial respiration in skeletal or cardiac muscle of mice lacking cellular prion protein

Cited by 17 publications

References 41 publications

Prion Protein Expression and Functional Importance in Skeletal Muscle

Prion Protein Expression and Functional Importance in Skeletal Muscle

Cellular Prion Protein Promotes Regeneration of Adult Muscle Tissue

Neurobehavioral Testing in Prion Disease Studies

Contact Info

Product

Resources

About