Diallyl disulfide impairs hippocampal neurogenesis in the young adult brain

Toxicol Lett. 2013 Jul 31;221(1):31-8. doi: 10.1016/j.toxlet.2013.05.013. Epub 2013 May 31.

Abstract

Garlic and garlic extracts are used as seasonings and are generally considered beneficial to human health, which include antioxidant and neuroprotective properties in neurological disorders. In the present study, we examined the effects of garlic sulfur components on the proliferation of neural progenitor cells (NPCs) and hippocampal neurogenesis. Of the sulfur compounds extracted, diallyl disulfide (DADS) significantly suppressed the proliferation of NPCs, whereas other sulfur containing components had no effect. In order to investigate the effect of DADS on adult hippocampal neurogenesis, DADS was administered orally to young (6 week-old) male C57BL/6 mice for 2 weeks. It was found that 10 mg/kg of DADS significantly decreased the proliferation of NPCs in the dentate gyrus without affecting the survival of newly generated cells. Furthermore, DADS decreased levels of hippocampal BDNF, phosphorylated CREB signaling, and phosphorylated ERKs, which are known to be related to hippocampal neurogenesis and NPCs proliferation. In addition, DADS induced significant memory defects as compared with controls. We report that DADS may have adverse effects on hippocampal neurogenesis and neurocognitive functions by modulating ERK and BDNF-CREB signaling, and suggest that the advisability of consuming large amounts of garlic products should be considered, particularly during the period of neural growth.

Keywords: 5′-bromo-2′-deoxyuridine; BDNF; Brain-derived neurotrophic factor; BrdU; CREB; DG; Diallyl disulfide; GCL; Hippocampal neurogenesis; Memory retention; NPCs; brain-derived neurotropic factor; cAMP-response element-binding protein; dentate gyrus; granular cell layer; neural progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / toxicity*
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • CREB-Binding Protein / metabolism
  • Cell Proliferation / drug effects
  • Cognition / drug effects
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / pathology
  • Disulfides / toxicity*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Garlic / chemistry
  • Male
  • Memory / drug effects
  • Memory Disorders / chemically induced
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • Neurogenesis / drug effects*
  • Phosphorylation
  • Plant Extracts / toxicity
  • Signal Transduction / drug effects

Substances

  • Allyl Compounds
  • Brain-Derived Neurotrophic Factor
  • Disulfides
  • Plant Extracts
  • diallyl disulfide
  • CREB-Binding Protein
  • Crebbp protein, mouse
  • Extracellular Signal-Regulated MAP Kinases