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Effects of cardiotrophin‐1 (CT‐1) in a mouse motor neuron disease
Author(s) -
Mitsumoto Hiroshi,
Klinkosz Bogdan,
Pioro Erik P.,
Tsuzaka Kazufumi,
Ishiyama Takeo,
O'Leary Rhona M.,
Pennica Diane
Publication year - 2001
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.1068
Subject(s) - motor neuron , medicine , choline acetyltransferase , grip strength , neurofilament , in vivo , neurotrophic factors , endocrinology , immunohistochemistry , biology , central nervous system , surgery , disease , receptor , microbiology and biotechnology
Cardiotrophin‐1 (CT‐1) has potent survival‐promoting effects on motor neurons in vitro and in vivo and may be effective in treating motor neuron diseases (MND). We investigated the effects of CT‐1 treatment in wobbler mouse MND. Wobbler mice were randomly assigned to receive subcutaneously injected CT‐1 (1 mg/kg, n = 18, in two experiments) or vehicle ( n = 18, in two experiments) daily, 6 times/week for 4 weeks after clinical diagnosis at age 3 to 4 weeks. Cardiotrophin‐1 treatment prevented deterioration in paw position and walking pattern abnormalities. Grip strength declined steadily in the vehicle group, whereas in the CT‐1 group it declined at week 1 but increased thereafter to exceed baseline strength by 5% ( P = 0.0002) at week 4. Running speed was faster with CT‐1 ( P = 0.007). Biceps muscle twitch tension, muscle weight, mean muscle fiber diameter, and intramuscular axonal sprouting were significantly greater with CT‐1 treatment than with vehicle treatment. Histometry revealed a trend that indicated CT‐1 modestly increased the number of immunoreactive motor neurons, as determined by both choline acetyltransferase and c‐Ret antibodies, and reduced the number of phosphorylated neurofilament immunoreactive perikarya ( P = 0.05). The number of large myelinated motor axons significantly increased with treatment (206 versus 113, P = 0.01). We conclude that CT‐1 exerts myotrophic effects as well as neurotrophic effects in a mouse model of spontaneous MND, a finding that has potential therapeutic implications for human MND. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 769–777, 2001