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BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

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Abstract

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.

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    Authors and Affiliations

    1. Animal Center, Kunming Medical University, Kunming, 650031, China

      Mei-Rong Chen, Ting-Hua Wang & Jia Liu

    2. Institute of Neuroscience, Molecular Clinic Institute, Kunming Medical University, Kunming, 650031, China

      Ping Dai, Shu-Fen Wang, Ya Zhao & Ting-Hua Wang

    3. Key Laboratory of National Physical Health and Altitude Training Adaptation in Yunnan Normal University, Kunming, 650000, China

      Shu-Hua Song & Hang-Ping Wang

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    M.-R. Chen, P. Dai, T.-H. Wang and J. Liu have contributed equally to this work.

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    Chen, MR., Dai, P., Wang, SF. et al. BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway. Neurochem Res 41, 2585–2597 (2016). https://doi.org/10.1007/s11064-016-1970-5

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