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Diallyl disulfide impairs hippocampal neurogenesis in the young adult brain
Authors:Seung Taek Ji  Min-Sun Kim  Hee Ra Park  Eunjin Lee  Yujeong Lee  Young Jung Jang  Hyung Sik Kim  Jaewon Lee
Affiliation:1. Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of Korea;2. Department of Pharmacy, College of Pharmacy, Sunchon National University, Sunchon 540-742, Republic of Korea
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:CREB, cAMP-response element-binding protein   BDNF, brain-derived neurotropic factor   BrdU, 5&prime  -bromo-2&prime  -deoxyuridine   DG, dentate gyrus   GCL, granular cell layer   NPCs, neural progenitor cells
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