Neuroprotective mechanisms of Lycium barbarum polysaccharides against ischemic insults by regulating NR2B and NR2A containing NMDA receptor signaling pathways

Zhongshan Shi, Lihui Zhu, Tingting Li, Xiaoya Tang, Yonghui Xiang, Xinjia Han, Luoxing Xia, Ling Zeng, Junhua Nie, Yongxia Huang, Chi Kwan Tsang, Ying Wang, Zhigang Lei, Zaocheng Xu, Kwok Fai So, Yiwen Ruan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Glutamate excitotoxicity plays an important role in neuronal death after ischemia. However, all clinical trials using glutamate receptor inhibitors have failed. This may be related to the evidence that activation of different subunit of NMDA receptor will induce different effects. Many studies have shown that activation of the intrasynaptic NR2A subunit will stimulate survival signaling pathways, whereas upregulation of extrasynaptic NR2B will trigger apoptotic pathways. A Lycium barbarum polysaccharide (LBP) is a mixed compound extracted from Lycium barbarum fruit. Recent studies have shown that LBP protects neurons against ischemic injury by anti-oxidative effects. Here we first reported that the effect of LBP against ischemic injury can be achieved by regulating NR2B and NR2A signaling pathways. By in vivo study, we found LBP substantially reduced CA1 neurons from death after transient global ischemia and ameliorated memory deficit in ischemic rats. By in vitro study, we further confirmed that LBP increased the viability of primary cultured cortical neurons when exposed to oxygen-glucose deprivation (OGD) for 4 h. Importantly, we found that LBP antagonized increase in expression of major proteins in the NR2B signal pathway including NR2B, nNOS, Bcl-2-associated death promoter (BAD), cytochrome C (cytC) and cleaved caspase-3, and also reduced ROS level, calcium influx and mitochondrial permeability after 4 h OGD. In addition, LBP prevented the downregulation in the expression of NR2A, pAkt and pCREB, which are important cell survival pathway components. Furthermore, LBP attenuated the effects of a NR2B co-agonist and NR2A inhibitor on cell mortality under OGD conditions. Taken together, our results demonstrated that LBP is neuroprotective against ischemic injury by its dual roles in activation of NR2A and inhibition of NR2B signaling pathways, which suggests that LBP may be a superior therapeutic candidate for targeting glutamate excitotoxicity for the treatment of ischemic stroke.

Original languageEnglish (US)
Article number288
JournalFrontiers in Cellular Neuroscience
Volume11
DOIs
StatePublished - Sep 27 2017

Fingerprint

Oxygen
Neurons
Glucose
Glutamic Acid
Wounds and Injuries
Ischemia
Lycium
lycium barbarum polysaccharide
NR2A NMDA receptor
Memory Disorders
Glutamate Receptors
Cytochromes
N-Methyl-D-Aspartate Receptors
Caspase 3
Permeability
Signal Transduction
Fruit
Cell Survival
Up-Regulation
Down-Regulation

Keywords

  • Apoptosis
  • Excitotoxicity
  • Ischemia
  • Lycium barbarum polysaccharides
  • NR2A
  • NR2B

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Neuroprotective mechanisms of Lycium barbarum polysaccharides against ischemic insults by regulating NR2B and NR2A containing NMDA receptor signaling pathways. / Shi, Zhongshan; Zhu, Lihui; Li, Tingting; Tang, Xiaoya; Xiang, Yonghui; Han, Xinjia; Xia, Luoxing; Zeng, Ling; Nie, Junhua; Huang, Yongxia; Tsang, Chi Kwan; Wang, Ying; Lei, Zhigang; Xu, Zaocheng; So, Kwok Fai; Ruan, Yiwen.

In: Frontiers in Cellular Neuroscience, Vol. 11, 288, 27.09.2017.

Research output: Contribution to journalArticle

Shi, Z, Zhu, L, Li, T, Tang, X, Xiang, Y, Han, X, Xia, L, Zeng, L, Nie, J, Huang, Y, Tsang, CK, Wang, Y, Lei, Z, Xu, Z, So, KF & Ruan, Y 2017, 'Neuroprotective mechanisms of Lycium barbarum polysaccharides against ischemic insults by regulating NR2B and NR2A containing NMDA receptor signaling pathways', Frontiers in Cellular Neuroscience, vol. 11, 288. https://doi.org/10.3389/fncel.2017.00288
Shi, Zhongshan ; Zhu, Lihui ; Li, Tingting ; Tang, Xiaoya ; Xiang, Yonghui ; Han, Xinjia ; Xia, Luoxing ; Zeng, Ling ; Nie, Junhua ; Huang, Yongxia ; Tsang, Chi Kwan ; Wang, Ying ; Lei, Zhigang ; Xu, Zaocheng ; So, Kwok Fai ; Ruan, Yiwen. / Neuroprotective mechanisms of Lycium barbarum polysaccharides against ischemic insults by regulating NR2B and NR2A containing NMDA receptor signaling pathways. In: Frontiers in Cellular Neuroscience. 2017 ; Vol. 11.
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AU - Tang, Xiaoya

AU - Xiang, Yonghui

AU - Han, Xinjia

AU - Xia, Luoxing

AU - Zeng, Ling

AU - Nie, Junhua

AU - Huang, Yongxia

AU - Tsang, Chi Kwan

AU - Wang, Ying

AU - Lei, Zhigang

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AU - So, Kwok Fai

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