BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.
Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.
Animal Center, Kunming Medical University, Kunming, 650031, China.
Mei-Rong
MR
Chen
Institute of Neuroscience, Molecular Clinic Institute, Kunming Medical University, Kunming, 650031, China.
Ping
P
Dai
Institute of Neuroscience, Molecular Clinic Institute, Kunming Medical University, Kunming, 650031, China.
Shu-Fen
SF
Wang
Key Laboratory of National Physical Health and Altitude Training Adaptation in Yunnan Normal University, Kunming, 650000, China.
Shu-Hua
SH
Song
Key Laboratory of National Physical Health and Altitude Training Adaptation in Yunnan Normal University, Kunming, 650000, China.
Hang-Ping
HP
Wang
Institute of Neuroscience, Molecular Clinic Institute, Kunming Medical University, Kunming, 650031, China.
Ya
Y
Zhao
Animal Center, Kunming Medical University, Kunming, 650031, China. tinghua_neuron@263.net.|Institute of Neuroscience, Molecular Clinic Institute, Kunming Medical University, Kunming, 650031, China. tinghua_neuron@263.net.
Ting-Hua
TH
Wang
Animal Center, Kunming Medical University, Kunming, 650031, China. liujiaaixuexi@126.com.
Jia
J
Liu
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D051057:Proto-Oncogene Proteins c-akt
BDNF-overexpression; Locomotor function; Spinal cord injury; Thermal hyperpathia