Blocking of BDNF-TrkB signaling inhibits the promotion effect of neurological function recovery after treadmill training in rats with spinal cord injury

Spinal Cord. 2019 Jan;57(1):65-74. doi: 10.1038/s41393-018-0173-0. Epub 2018 Jul 12.

Abstract

Study design: Experimental study.

Objectives: To investigate the role of BDNF-TrkB signaling that promotes the recovery of neurological function in rats with incomplete spinal cord injury (SCI) after treadmill training (TT).

Setting: Rehabilitation Medicine Center of the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Methods: Forty rats were divided into five groups: (i) Sham; (ii) SCI and phosphate-buffered saline (PBS) (SCI/PBS); (iii) SCI-TT/PBS; (iv) SCI/TrkB-IgG; and (v) SCI-TT/TrkB-IgG. The intrathecal catheter and T10 contusion SCI model was established. At 7-day post SCI, the BDNF-TrkB signaling was blocked by TrkB-IgG. Exercise began at 8th day after SCI and continued for 4 weeks. The BBB scale and motor-evoked potential (MEP) were used for the evaluation of the locomotor functions. The BDNF/TrkB, PSD-95, SYP synthesis, and neuroprotective effect was determined by western blot, Nissl, or immunohistochemistry staining.

Results: The expression of BDNF and TrkB in the SCI-TT/PBS group was 1.46 ± 0.09 and 1.70 ± 0.22, respectively, higher than that in SCI/PBS group (0.51 ± 0.04 and 0.76 ± 0.07, respectively), relative to the Sham group. The BBB scores in the Sham, SCI/PBS, SCI-TT/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG groups were 21.00 ± 0.00, 7.63 ± 0.74, 12.13 ± 1.36, 7.88 ± 0.64, and 8.75 ± 0.88, respectively. The percentages of MEP responders/non-responders were 100, 0, 75, 0, and 50%. The MEP latencies in Sham, SCI-TT/PBS, and SCI-TT/TrkB-IgG groups were 6.65 ± 0.19, 13.32 ± 2.95, and 19.55 ± 4.55 ms, respectively. The number of NeuN+ neurons, the cell body area of motor neurons, PSD-95, and SYP expression in the SCI-TT/PBS group was significantly higher than that in the SCI/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG groups.

Conclusion: The BDNF-TrkB signaling is a critical pathway in exercise training that promotes the recovery of neurological function in rats with incomplete SCI.

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism
  • Brain-Derived Neurotrophic Factor / antagonists & inhibitors
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Disease Models, Animal
  • Disks Large Homolog 4 Protein / metabolism
  • Evoked Potentials, Motor
  • Exercise Therapy*
  • Female
  • Gene Expression
  • Immunoglobulin G
  • Motor Activity / physiology
  • Nerve Tissue Proteins / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Receptor, trkB / antagonists & inhibitors
  • Receptor, trkB / metabolism*
  • Recovery of Function / physiology*
  • Signal Transduction
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / rehabilitation*
  • Synaptophysin / metabolism

Substances

  • Antigens, Nuclear
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Immunoglobulin G
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat
  • Synaptophysin
  • Syp protein, rat
  • Ntrk2 protein, rat
  • Receptor, trkB