Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA.

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA.
Exp Neurol. 2015 Apr 27;
Authors: Halievski K, Henley CL, Domino L, Poort JE, Fu M, Katsuno M, Adachi H, Sobue G, Breedlove SM, Jordan CL
Abstract
Transgenic expression of neurotrophic factors in skeletal muscle has been found to protect mice from neuromuscular disease, including spinal bulbar muscular atrophy (SBMA), triggering renewed interest in neurotrophic factors as therapeutic agents for treating neuromuscular disease. Because SBMA is an androgen-dependent disease, and brain-derived neurotrophic factor (BDNF) mediates effects of androgens on neuromuscular systems, we asked whether BDNF expression is impaired in two different transgenic (Tg) mouse models of SBMA, the so called "97Q" and "myogenic" SBMA models. The 97Q model globally overexpresses a full length human AR with 97 glutamine repeats whereas the myogenic model of SBMA overexpresses a wild-type rat androgen receptor (AR) only in skeletal muscle fibers. Using quantitative PCR, we find that muscle BDNF mRNA declines in an androgen-dependent manner in both models, paralleling changes in motor function, with robust deficits (6-8 fold) in both fast and slow twitch muscle of impaired Tg males. Castration rescues or reverses disease-related deficits in muscle BDNF mRNA in both models, paralleling its effect on motor function. Moreover, when disease is acutely induced in Tg females, both motor function a...

Source: Experimental Neurology - April 27, 2015 Category: Neurology Authors: Halievski K, Henley CL, Domino L, Poort JE, Fu M, Katsuno M, Adachi H, Sobue G, Breedlove SM, Jordan CL Tags: Exp Neurol Source Type: research