Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury.

Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non-skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine. We tested the hypothesis that glutamine preserves muscle function after SCI and that this is associated with increased heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα). Changes in plantarflexor force, fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFα muscle protein levels were measured 7 days after sham or spinal cord transection surgery in mice receiving daily placebo or glutamine. Compared with placebo, after SCI glutamine significantly attenuated the reductions in maximal isometric force (0.22 ± 0.01 versus 0.31 ± 0.03 N, respectively) and fatigue resistance (34 ± 4 versus 59 ± 4% of initial force, respectively). Glutamine significantly ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal cord transection was associated with decreased Hsp70 and Hsp25 with glutamine only (45 ± 3 and 44 ± 5% of placebo, respectively). Glutamine significantly reduced spinal cord transection-associated increases in IL-6 and TNFα compared with placebo (38 ± 6 and 37 ± 8% of placebo, respectively). Functionally, early reductions in contractile protein, force and fatigue resistance after SCI were reversed with glutamine. Spinal cord transection-associated reductions in Hsp70, Hsp25, IL-6 and TNFα with glutamine versus placebo suggest lower stress in the muscle, possibly related to a reduced need to produce glutamine. These findings support glutamine as a therapeutic intervention to accelerate recovery of muscle function after SCI.