ABSTRACT
Capsaicin (N-vanillyl-8-methyl-1-nonenamide) is a major pungent ingredient in hot peppers and induces apoptosis in malignant carcinoma cell lines. However, the adverse effects of capsaicin on neuronal development have not been fully explored. The aim of this study was to determine whether capsaicin affected murine-derived cerebellar multi-potent neural progenitor cells (NPC) or adult hippocampal neurogenesis in vivo. Capsaicin dose-dependently suppressed NPC proliferation, and higher concentrations were cytotoxic. Capsaicin decreased the activation of extracellular signal-regulated kinases (ERK) without markedly affecting p38 kinases. Capsaicin reduced the number of newly generated cells in the dentate gyrus of the hippocampus but did not significantly alter learning and memory performance in young adult mice. Interestingly, capsaicin decreased ERK activation in the hippocampus, suggesting that reduced ERK signaling may be involved in the capsaicin-mediated regulation of hippocampal neurogenesis.
Subject(s)
Capsaicin/toxicity , Hippocampus/drug effects , Multipotent Stem Cells/drug effects , Neurons/drug effects , Sensory System Agents/toxicity , Animals , Brain/drug effects , Brain/metabolism , Brain/pathology , Brain Chemistry , Bromodeoxyuridine/metabolism , Cell Line, Transformed , Cell Proliferation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression/genetics , Hippocampus/growth & development , Hippocampus/pathology , Male , Maze Learning/drug effects , Memory/drug effects , Mice , Mice, Inbred C57BL , RNA, Messenger/metabolism , Swimming , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
2-Deoxy-d-glucose (2DG) is an analog of glucose that is effectively taken up by cells competing with normal glucose but cannot be further utilized to produce energy. It was previously reported that 2DG can mimic the beneficial effects of dietary restriction in experimental models of neurodegenerative disorders and cancer. In the present study, we report that pretreatment with 2DG increases the resistance of neural progenitor cells (NPC) to oxidative insults. 2DG significantly suppressed the proliferation of NPC, and high concentrations of 2DG were toxic to NPC. However, a treatment with a moderate concentration of 2DG protected the NPC against tBHP-induced oxidative stress suggesting that this chemical had hormetic action mimicking dietary restriction. Furthermore, we showed that the protective mechanism of 2DG involved the activation of AMP-activated protein kinase. Our findings demonstrate that 2DG can modulate the cellular responses to oxidative stress and confer cellular resistance in NPC by activating the metabolic regulator.
