PMID- 24505322
OWN - NLM
STAT- MEDLINE
DCOM- 20141108
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 2
DP  - 2014
TI  - Effects of the ss2-adrenoceptor agonist, albuterol, in a mouse model of anti-MuSK 
      myasthenia gravis.
PG  - e87840
LID - 10.1371/journal.pone.0087840 [doi]
LID - e87840
AB  - The beta2-adrenergic receptor agonist, albuterol, has been reported beneficial in 
      treating several forms of congenital myasthenia. Here, for the first time, we 
      examined the potential benefit of albuterol in a mouse model of anti-Muscle 
      Specific Kinase (MuSK) myasthenia gravis. Mice received 15 daily injections of 
      IgG from anti-MuSK positive patients, which resulted in whole-body weakness. At 
      neuromuscular junctions in the tibialis anterior and diaphragm muscles the 
      autoantibodies caused loss of postsynaptic acetylcholine receptors, and reduced 
      the amplitudes of the endplate potential and spontaneous miniature endplate 
      potential in the diaphragm muscle. Treatment with albuterol (8 mg/kg/day) during 
      the two-week anti-MuSK injection series reduced the degree of weakness and weight 
      loss, compared to vehicle-treated mice. However, the compound muscle action 
      potential recorded from the gastrocnemius muscle displayed a decremental response 
      in anti-MuSK-injected mice whether treated with albuterol or vehicle. Ongoing 
      albuterol treatment did not increase endplate potential amplitudes compared to 
      vehicle-treated mice nor did it prevent the loss of acetylcholine receptors from 
      motor endplates. On the other hand, albuterol treatment significantly reduced the 
      degree of fragmentation of endplate acetylcholine receptor clusters and increased 
      the extent to which the remaining receptor clusters were covered by 
      synaptophysin-stained nerve terminals. The results provide the first evidence 
      that short-term albuterol treatment can ameliorate weakness in a robust mouse 
      model of anti-MuSK myasthenia gravis. The results also demonstrate that it is 
      possible for albuterol treatment to reduce whole-body weakness without 
      necessarily reversing myasthenic impairment to the structure and function of the 
      neuromuscular junction.
FAU - Ghazanfari, Nazanin
AU  - Ghazanfari N
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Morsch, Marco
AU  - Morsch M
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Tse, Nigel
AU  - Tse N
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Reddel, Stephen W
AU  - Reddel SW
AD  - Department of Molecular Medicine, Concord Hospital, Concord, New South Wales, 
      Australia.
FAU - Phillips, William D
AU  - Phillips WD
AD  - Physiology and Bosch Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140205
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Autoantibodies)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - QF8SVZ843E (Albuterol)
SB  - IM
MH  - Adrenergic beta-2 Receptor Agonists/*pharmacology
MH  - Albuterol/*pharmacology
MH  - Animals
MH  - Autoantibodies/immunology/*toxicity
MH  - Female
MH  - Humans
MH  - Mice
MH  - Muscle, Skeletal/immunology/pathology
MH  - Myasthenia Gravis, Autoimmune, Experimental/chemically induced/*drug 
      therapy/immunology/pathology
MH  - Neuromuscular Junction/immunology/pathology
MH  - Receptor Protein-Tyrosine Kinases/immunology
PMC - PMC3914858
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/02/08 06:00
MHDA- 2014/11/09 06:00
PMCR- 2014/02/05
CRDT- 2014/02/08 06:00
PHST- 2013/10/07 00:00 [received]
PHST- 2013/12/31 00:00 [accepted]
PHST- 2014/02/08 06:00 [entrez]
PHST- 2014/02/08 06:00 [pubmed]
PHST- 2014/11/09 06:00 [medline]
PHST- 2014/02/05 00:00 [pmc-release]
AID - PONE-D-13-41031 [pii]
AID - 10.1371/journal.pone.0087840 [doi]
PST - epublish
SO  - PLoS One. 2014 Feb 5;9(2):e87840. doi: 10.1371/journal.pone.0087840. eCollection 
      2014.