We will evaluate the functional significance of gender differences in the phenotype of fibers of the adult rabbit masseter muscle. Torques applied to the mandible by different neuromuscular compartments in adult males and females will be measured as an assay of masseter function. Torques produced by intramuscular microstimulation or during natural rhythmic activations of the masseter will be studied. We will study both orthograde and retrograde signaling mechanisms in the development of these gender differences. We will use high spatial resolution EMG methods to study the activity patterns of masseteric motoneurons in young and fully mature animals to determine whether changed in this orthograde signal accompany or precede changes in muscle fiber phenotype. We will attenuate or eliminate this orthograde signal by blocking neuromuscular synaptic transmission with botulinum toxin in young animals. Based on the available evidence, neurotrophin 4 (NT-4) is currently the best candidate for a retrograde signaling molecule used by motoneurons. We will determine whether NT-4 regulation accompanies or precedes the development of gender differences in masseter muscle fiber phenotype at both the protein and mRNA levels. We will use exogenous NT-4 and blockers of both NT-4 and other trk B ligands to manipulate available quantities of this putative retrograde signal and then study its effect on the development of gender differences in masseter muscle fiber phenotype. The results of these experiments will generate important new knowledge that will contribute significantly to our understanding of the structure and function of the muscles of mastication. Study of this animal model of human mastication will provide important new insights into the cellular mechanisms used by these unique muscles to regulate both their structure and function in different genders. The new knowledge generated will impact significantly several areas of clinical dentistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE011536-06
Application #
6379782
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Kousvelari, Eleni
Project Start
1995-09-30
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
6
Fiscal Year
2001
Total Cost
$244,238
Indirect Cost
Name
Emory University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Widmer, C G; English, A W; Morris-Wiman, J (2007) Developmental and functional considerations of masseter muscle partitioning. Arch Oral Biol 52:305-8
English, Arthur W; Widmer, Charles G (2003) Sex differences in rabbit masseter motoneuron firing behavior. J Neurobiol 55:331-40
Widmer, C G; Carrasco, D I; English, A W (2003) Differential activation of neuromuscular compartments in the rabbit masseter muscle during different oral behaviors. Exp Brain Res 150:297-307
English, Arthur W; Widmer, Charles G (2003) Sex differences in rabbit masseter muscle function. Cells Tissues Organs 174:87-96
Widmer, C G; English, A W; Carrasco, D I et al. (2002) Modeling rabbit temporomandibular joint torques during a power stroke. Angle Orthod 72:331-7
English, Arthur W; Schwartz, Gail (2002) Development of sex differences in the rabbit masseter muscle is not restricted to a critical period. J Appl Physiol 92:1214-22
Pol-Rodriguez, M M; Schwartz, G A; English, A W (2001) Post-translational phosphorylation of the slow/beta myosin heavy chain isoform in adult rabbit masseter muscle. J Muscle Res Cell Motil 22:513-9
Reader, M; Schwartz, G; English, A W (2001) Brief exposure to testosterone is sufficient to induce sex differences in the rabbit masseter muscle. Cells Tissues Organs 169:210-7
Eason, J M; Schwartz, G A; Pavlath, G K et al. (2000) Sexually dimorphic expression of myosin heavy chains in the adult mouse masseter. J Appl Physiol 89:251-8
Eason, J M; Schwartz, G; Shirley, K A et al. (2000) Investigation of sexual dimorphism in the rabbit masseter muscle showing different effects of androgen deprivation in adult and young adult animals. Arch Oral Biol 45:683-90

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