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Antidepressant-like effect of Ganoderma lucidum spore polysaccharide-peptide mediated by upregulation of prefrontal cortex brain-derived neurotrophic factor

A Correction to this article was published on 26 November 2021

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A 28-kDa polysaccharide-peptide (PGL) with antidepressant-like activities was isolated from spores of the mushroom Ganoderma lucidum. It was unadsorbed on DEAE-cellulose. Its internal amino acid sequences manifested pronounced similarity with proteins from the mushrooms Lentinula edodes and Agaricus bisporus. The monosaccharides present in 28-kDa PGL comprised predominantly of glucose (over 90%) and much fewer galactose, mannose residues, and other residues. PGL manifested antidepressant-like activities as follows. It enhanced viability and DNA content in corticosterone-injured PC12 cells(a cell line derived from a pheochromocytoma of the rat adrenal medulla with an embryonic origin from the neural crest containing a mixture of neuroblastic cells and eosinophilic cells) and reduced LDH release. A single acute PGL treatment shortened the duration of immobility of mice in both tail suspension and forced swimming tests. PGL treatment enhanced sucrose preference and shortened the duration of immobility in mice exposed to chronic unpredictable mild stress (CUMS). Chronic PGL treatment reversed the decline in mouse brain serotonin and norepinephrine levels but did not affect dopamine levels. PGL decreased serum corticosterone levels and increased BDNF mRNA and protein levels and increased synapsin I and PSD95 levels in the prefrontal cortex. This effect was completely blocked by pretreatment with the BDNF antagonist K252a, indicating that PGL increased synaptic proteins in a BDNF-dependent manner.

Key points

An antidepressive polysaccharide-peptide PGL was isolated from G. lucidum spores.

PGL protected PC12 nerve cells from the toxicity of corticosterone.

PGL upregulated BDNF expression and influenced key factors in the prefrontal cortex.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request (including its supplementary information files).

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This study was funded by Collaborative Innovation Center of Beijing Academy of Agricultural and Forestry Sciences [grant numbers KJCX201915] and Beijing Academy of Agriculture and Forestry Science [grant numbers KJCX20200208].

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Authors and Affiliations



S.Z. and L.Y designed research. S.Z., L.W., and X.L. conducted purification experiments. C.R., Y.G., and S.S. conducted animal experiments. S.Z., J.H.W., and T.N. prepared all the manuscript, H.W., Y.L., and L.Y. participated in the manuscript editing. All the authors have read and agreed to the published vision of manuscript.

Corresponding authors

Correspondence to Hexiang Wang, Litao Yi or Tzibun Ng.

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Ethical approval

All animal experiments procedures had been approved and were performed in accordance with the published guidelines of the China Council on Animal Care (Regulations for the Administration of Affairs Concerning Experimental Animals, approved by the State Council on 31 October, 1988, and promulgated by Decree No. 2 of the State Science and Technology Commission on 14 November, 1988).

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The authors declare no competing interests.

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Zhao, S., Rong, C., Gao, Y. et al. Antidepressant-like effect of Ganoderma lucidum spore polysaccharide-peptide mediated by upregulation of prefrontal cortex brain-derived neurotrophic factor. Appl Microbiol Biotechnol 105, 8675–8688 (2021).

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  • Ganoderma lucidum spores
  • Polysaccharide-peptide
  • Antidepressant
  • Monoamine neurotransmitters
  • Corticosterone
  • Brain-derived neurotrophic factor