Abstract
Neuromuscular junction destabilization following nerve injury contributes to irreversible functional impairment. Myogenic Regulatory Factors (MRF's) including myoblast determination factor (MyoD), MRF-4, Myogenin, and myogenic factors-5 (myf-5), and Growth-associated protein 43 KDa (GAP43) regulate gene expression of nicotinic acetylcholine receptor (nAChR) subunits (alpha, beta, delta, gamma, and epsilon). We hypothesized that nerve injury induces altered gene expression of MRF's, nAChRs, and GAP-43 in the skeletal muscle which destabilize neuromuscular junctions. The tibial nerve was transected in 42 juvenile male Sprague-Dawley rats. Denervated and contralateral control gastrocnemius m. mRNA for nAChR subunits, MRF's, and GAP-43 were determined by real time reverse transcription polymerase chain reaction (real time RT-PCR). After transection, muscle mass decreased for 1 year with a nadir of 75% at 3 months. Alpha, gamma, and epsilon subunit genes increased by 3 and peaked at 7 days before returning to control levels (P < 0.05). Beta subunits and GAP-43 tended to increase. Delta subunits peaked at 3 days returning to control levels by 30 days. By one month, most of the nAChR subunits had returned to control levels. Alpha, beta, gamma, and delta subunit expression remained significantly lower than control up to 1 year later (P < 0.05). MRF4, Myogenin, and MyoD expression paralleled that of alpha, gamma, and epsilon nAChR subunits (P < 0.05). Gene expression of nAChR alpha, gamma, delta and epsilon subunits was biphasic in the first month after nerve injury, similar to that of MRF's. nAChR subunits and MRF's may play a critical role in neuromuscular junction stability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1498-1505 |
| Number of pages | 8 |
| Journal | Journal of Orthopaedic Research |
| Volume | 25 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2007 |
| Externally published | Yes |
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Keywords
- Acetylcholine receptor
- GAP-43
- Myogenic regulatory factor
- Nerve injury
- Rat
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
Cite this
Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model. / Ma, Jianjun; Shen, Jian; Garrett, Jeffrey P.; Lee, Cassandra A; Li, Zhongyu; Elsaidi, Gamal A.; Ritting, Andrew; Hick, Jeffrey; Tan, Kim H.; Smith, Thomas L.; Smith, Beth P.; Koman, L. Andrew.
In: Journal of Orthopaedic Research, Vol. 25, No. 11, 11.2007, p. 1498-1505.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model
AU - Ma, Jianjun
AU - Shen, Jian
AU - Garrett, Jeffrey P.
AU - Lee, Cassandra A
AU - Li, Zhongyu
AU - Elsaidi, Gamal A.
AU - Ritting, Andrew
AU - Hick, Jeffrey
AU - Tan, Kim H.
AU - Smith, Thomas L.
AU - Smith, Beth P.
AU - Koman, L. Andrew
PY - 2007/11
Y1 - 2007/11
N2 - Neuromuscular junction destabilization following nerve injury contributes to irreversible functional impairment. Myogenic Regulatory Factors (MRF's) including myoblast determination factor (MyoD), MRF-4, Myogenin, and myogenic factors-5 (myf-5), and Growth-associated protein 43 KDa (GAP43) regulate gene expression of nicotinic acetylcholine receptor (nAChR) subunits (alpha, beta, delta, gamma, and epsilon). We hypothesized that nerve injury induces altered gene expression of MRF's, nAChRs, and GAP-43 in the skeletal muscle which destabilize neuromuscular junctions. The tibial nerve was transected in 42 juvenile male Sprague-Dawley rats. Denervated and contralateral control gastrocnemius m. mRNA for nAChR subunits, MRF's, and GAP-43 were determined by real time reverse transcription polymerase chain reaction (real time RT-PCR). After transection, muscle mass decreased for 1 year with a nadir of 75% at 3 months. Alpha, gamma, and epsilon subunit genes increased by 3 and peaked at 7 days before returning to control levels (P < 0.05). Beta subunits and GAP-43 tended to increase. Delta subunits peaked at 3 days returning to control levels by 30 days. By one month, most of the nAChR subunits had returned to control levels. Alpha, beta, gamma, and delta subunit expression remained significantly lower than control up to 1 year later (P < 0.05). MRF4, Myogenin, and MyoD expression paralleled that of alpha, gamma, and epsilon nAChR subunits (P < 0.05). Gene expression of nAChR alpha, gamma, delta and epsilon subunits was biphasic in the first month after nerve injury, similar to that of MRF's. nAChR subunits and MRF's may play a critical role in neuromuscular junction stability.
AB - Neuromuscular junction destabilization following nerve injury contributes to irreversible functional impairment. Myogenic Regulatory Factors (MRF's) including myoblast determination factor (MyoD), MRF-4, Myogenin, and myogenic factors-5 (myf-5), and Growth-associated protein 43 KDa (GAP43) regulate gene expression of nicotinic acetylcholine receptor (nAChR) subunits (alpha, beta, delta, gamma, and epsilon). We hypothesized that nerve injury induces altered gene expression of MRF's, nAChRs, and GAP-43 in the skeletal muscle which destabilize neuromuscular junctions. The tibial nerve was transected in 42 juvenile male Sprague-Dawley rats. Denervated and contralateral control gastrocnemius m. mRNA for nAChR subunits, MRF's, and GAP-43 were determined by real time reverse transcription polymerase chain reaction (real time RT-PCR). After transection, muscle mass decreased for 1 year with a nadir of 75% at 3 months. Alpha, gamma, and epsilon subunit genes increased by 3 and peaked at 7 days before returning to control levels (P < 0.05). Beta subunits and GAP-43 tended to increase. Delta subunits peaked at 3 days returning to control levels by 30 days. By one month, most of the nAChR subunits had returned to control levels. Alpha, beta, gamma, and delta subunit expression remained significantly lower than control up to 1 year later (P < 0.05). MRF4, Myogenin, and MyoD expression paralleled that of alpha, gamma, and epsilon nAChR subunits (P < 0.05). Gene expression of nAChR alpha, gamma, delta and epsilon subunits was biphasic in the first month after nerve injury, similar to that of MRF's. nAChR subunits and MRF's may play a critical role in neuromuscular junction stability.
KW - Acetylcholine receptor
KW - GAP-43
KW - Myogenic regulatory factor
KW - Nerve injury
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=36749053484&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36749053484&partnerID=8YFLogxK
U2 - 10.1002/jor.20414
DO - 10.1002/jor.20414
M3 - Article
C2 - 17568415
AN - SCOPUS:36749053484
VL - 25
SP - 1498
EP - 1505
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
SN - 0736-0266
IS - 11
ER -