Laboratory Animal Research (Dec 2016)

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection

  • Eun-Kyoung Koh,
  • Woo-Bin Yun,
  • Ji-Eun Kim,
  • Sung-Hwa Song,
  • Ji-Eun Sung,
  • Hyun-Ah Lee,
  • Eun-Ji Seo,
  • Seung-Wan Jee,
  • Chang-Joon Bae,
  • Dae-Youn Hwang

DOI
https://doi.org/10.5625/lar.2016.32.2.105
Journal volume & issue
Vol. 32, no. 2
pp. 105 – 115

Abstract

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Abstract To investigate the beneficial effects of diosgenin (DC) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DC for 21 days. Multiple types of damage were successfully induced by Aß-42 accumulation and TMT injection into the brains of TG mice. However, DC treatment significantly reduced the number of Aß-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DC treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75NTR expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DC could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis.

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