BDNF Activates mTOR to Upregulate NR2B Expression in the Rostral Anterior Cingulate Cortex Required for Inflammatory Pain-Related Aversion in Rats

Abstract

The mechanistic target of rapamycin (mTOR) has been demonstrated to mediate pain-related aversion induced by formalin in the rostral anterior cingulate cortex (rACC). However, it remains unclear the signaling pathways and regulatory proteins involved. In the rACC, brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator, has been shown to play a role in the development and persistence of chronic pain. In this study, we used a rat formalin-induced inflammatory pain model to demonstrate BDNF up-regulation in the rACC. Stimulation with exogenous BDNF up-regulated mTOR, whilst cyclotraxin B (CTX-B), a tropomyosin receptor kinase B (TrkB) antagonist, down-regulated mTOR. Our results suggest BDNF could activate an mTOR signaling pathway. Subsequently, we used formalin-induced conditioned place avoidance (F-CPA) training in rat models to investigate if mTOR activation was required for pain-related aversion. We demonstrated that BDNF/mTOR signaling could activate the NMDA receptor subunit episilon-2 (NR2B), which is required for F-CPA. Our results reveal that BDNF activates mTOR to up-regulate NR2B expression, which is required for inflammatory pain-related aversion in the rACC of rats.

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Adapted from Jones et al. 2008. (Color figure online)

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Acknowledgements

The present work was supported by the Natural Science Foundation of Shandong Province (2013ZRB14282), the Key Researchand Development Project of Shandong Province (2014GGH218033) and the National Natural Science Foundation of China (NSFC, 30872433).

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Correspondence to Mengyuan Zhang.

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Zhang, Y., Ji, F., Wang, G. et al. BDNF Activates mTOR to Upregulate NR2B Expression in the Rostral Anterior Cingulate Cortex Required for Inflammatory Pain-Related Aversion in Rats. Neurochem Res 43, 681–691 (2018). https://doi.org/10.1007/s11064-018-2470-6

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Keywords

  • Rostral anterior cingulate cortex
  • Rapamycin
  • Brain-derived neurotrophic factor
  • Pain-related aversion
  • NMDA receptors
  • NR2B