Gastrodin Protects Neural Progenitor Cells Against Amyloid β (1-42)-Induced Neurotoxicity and Improves Hippocampal Neurogenesis in Amyloid β (1-42)-Injected Mice.

Abstract

The aim of this study was to investigate the neuroprotective effects of gastrodin (GAS), one of the major bioactive components of Gastrodia elata Blume (Tian Ma), against amyloid β (Aβ) (1-42)-induced neurotoxicity in primary neural progenitor cells (NPCs). We found that pretreatment with GAS not only prevents a loss in cell viability following treatment with Aβ (1-42) but also counteracts Aβ (1-42)-triggered release of pro-inflammatory cytokines and nitric oxide (NO) in a dose-dependent manner. Additionally, GAS was able to attenuate Aβ (1-42)-induced apoptosis in NPCs, evidenced by the decreased percentage of apoptotic cells and altered expression of apoptosis-related proteins in response to GAS pretreatment prior to Aβ (1-42) exposure. Furthermore, in Aβ (1-42)-injected C57BL/6 mice, we found that systemic administration of GAS could improve hippocampal neurogenesis, manifested by the increased number of SOX-2 and doublecortin (DCX)-positive cells in the DG area. Mechanistic studies revealed that in NPCs, GAS could reverse the Aβ (1-42)-induced increase in phosphorylation of MEK-1/2, extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinase (JNK). When combining GAS with the MEK inhibitor U0126 or the JNK inhibitor SP600125, we observed a synergistic effect against Aβ (1-42)-induced reduction in cell viability of NPCs. Taken together, these results show the efficacy and underlying mechanism of GAS against amyloid β (1-42)-induced neurotoxicity and provide substantial insight into the potential merits of GAS for its clinical application in the treatment of Alzheimer's disease.

• Authors: Meng Li, Sumin Qian
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 60 Issue 1 Pg. 21-32 (Sep 2016) ISSN: 1559-1166 [Electronic] United States
• PMID: 27112440 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• Benzyl Alcohols
• Cytokines
• DCX protein, human
• Dcx protein, mouse
• Doublecortin Domain Proteins
• Doublecortin Protein
• Glucosides
• Microtubule-Associated Proteins
• Neuropeptides
• Neuroprotective Agents
• Peptide Fragments
• SOXB1 Transcription Factors
• Sox2 protein, mouse
• amyloid beta-protein (1-42)
• Nitric Oxide
• gastrodin
• Mitogen-Activated Protein Kinases

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Apoptosis
• Benzyl Alcohols (pharmacology)
• Cell Line, Tumor
• Cells, Cultured
• Cytokines (metabolism)
• Doublecortin Domain Proteins
• Doublecortin Protein
• Glucosides (pharmacology)
• Hippocampus (cytology, drug effects, metabolism)
• Humans
• Mice
• Mice, Inbred C57BL
• Microtubule-Associated Proteins (genetics, metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Neural Stem Cells (drug effects, metabolism)
• Neurogenesis
• Neuropeptides (genetics, metabolism)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide (metabolism)
• Peptide Fragments (toxicity)
• SOXB1 Transcription Factors (genetics, metabolism)