The effect of periaqueductal gray’s metabotropic glutamate receptor subtype 8 activation on locomotor function following spinal cord injury

Abstract

Abstract Background and aims The pathophysiology of spinal cord injury is very complex. One of the debilitating aspects of spinal cord injury in addition to pain is a defect in motor function below the lesion surface. In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, on animal’s locomotor functions in a model of compression spinal cord injury. Methods We used a contusion method (T6-T8) for induction of spinal cord injury. Male Wistar rats were randomly assigned to five equal groups (n = 10 per group). Clips compression injury model was used to induce spinal cord injury. Three weeks post injury DCPG, siRNA (small interfering Ribonucleic Acid) and normal saline (vehicle) were administered intra-ventrolaterally to the periaqueductal gray (PAG) region. Motor function, were assessed through BBB (Basso, Beattie, and Bresnahan Locomotor Rating Scale) and ladder walking test. In addition, the effects of DCPG on axonal regeneration in corticospinal tract were evaluated. Results We found that DCPG could improve motor function and axonal regeneration in corticospinal tract when compared to siRNA group. Conclusions The results revealed that activation of mGluR8 in PAG is capable to improve motor function and of axonal regeneration due to the inhibitory effect on glutamate transmission on the spinal cord surface and also the elimination of the deleterious effect of glutamate on the regeneration of the injured area as an excitatory neurotransmitter. Implications Our findings in this study showed that, more attention should be paid to glutamate and its receptors in spinal cord injury studies, whether at the spinal or cerebral level, especially in the field of motor function after spinal cord injury.