Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress

  • Authors:
    • Li‑Li Ji
    • Jun‑Bo Peng
    • Chang‑Hai Fu
    • Lei Tong
    • Zhen‑Yu Wang
  • View Affiliations

  • Published online on: August 7, 2017     https://doi.org/10.3892/mmr.2017.7185
  • Pages: 4987-4993
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Abstract

Accumulating evidence has demonstrated that the σ-1 receptor (σ‑1R) possesses neuroprotective effects and is a potential novel therapeutic target for certain psychiatric diseases, including post‑traumatic stress disorder (PTSD) accompanied with anxiety disorder. It has been reported that σ‑1R agonist treatment could be modulated by the brain‑derived neurotrophic factor (BDNF) signaling pathway. However, it remains unclear whether BDNF and its upstream regulator are mechanistically involved in the therapeutic effect of σ‑1R in PTSD. To address this question, rats were subjected to a single‑prolonged stress (SPS) paradigm and σ‑1R agonist administration. Open‑field and elevated plus maze tests were implemented to evaluate the effect of σ‑1R activation on the improvement of anxiety‑like behaviors. Furthermore, the expression levels of BDNF, phosphorylated cAMP responsive element‑binding protein (CREB) and glutamate receptor ionotropic N‑methyl D‑aspartate 2A (NMDAR2A) were investigated in the hippocampi of rats. It was revealed that the downregulation of BDNF, phosphorylated CREB and NMDAR2A induced by SPS were reversed by σ‑1R activation. Collectively, the results of the present study suggest that the NMDAR2A/CREB/BDNF signaling pathway is involved in the activation of σ‑1R resulting in therapeutic effects for PTSD.

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October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ji LL, Peng JB, Fu CH, Tong L and Wang ZY: Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress. Mol Med Rep 16: 4987-4993, 2017.
APA
Ji, L., Peng, J., Fu, C., Tong, L., & Wang, Z. (2017). Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress. Molecular Medicine Reports, 16, 4987-4993. https://doi.org/10.3892/mmr.2017.7185
MLA
Ji, L., Peng, J., Fu, C., Tong, L., Wang, Z."Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress". Molecular Medicine Reports 16.4 (2017): 4987-4993.
Chicago
Ji, L., Peng, J., Fu, C., Tong, L., Wang, Z."Sigma-1 receptor activation ameliorates anxiety-like behavior through NR2A-CREB-BDNF signaling pathway in a rat model submitted to single-prolonged stress". Molecular Medicine Reports 16, no. 4 (2017): 4987-4993. https://doi.org/10.3892/mmr.2017.7185