title: Diallyl disulfide impairs hippocampal neurogenesis in the young adult brain.
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.
authors.affiliation: 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.
authors.forename: Seung Taek
authors.initials: ST
authors.lastname: Ji
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Hee Ra
authors.initials: HR
authors.lastname: Park
authors.forename: Eunjin
authors.initials: E
authors.lastname: Lee
authors.forename: Yujeong
authors.initials: Y
authors.lastname: Lee
authors.forename: Young Jung
authors.initials: YJ
authors.lastname: Jang
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
mesh_terms: D000498:Allyl Compounds / Q000633:toxicity*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004220:Disulfides / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005737:Garlic / Q000737:chemistry; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000498:Allyl Compounds; D019208:Brain-Derived Neurotrophic Factor; D004220:Disulfides; D010936:Plant Extracts; C028009:diallyl disulfide; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases
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