Role of Akt and ERK signaling in the neurogenesis following brain ischemia.
Generation of the neural precursors persists throughout life in the forebrain subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ) in rodent and human brains. In addition, newborn granule cells in the hippocampal DG are important for learning and memory formation. Brain injuries such as seizure and trauma could trigger the endogenous programs for neurogenesis in the adult brain. Although brain ischemia also stimulates the proliferation of neural progenitor cells in SVZ and SGZ, the most neural progenitor cells are dead within a few days after generation. In addition, there is no therapeutic agent to promote the neurogenesis following brain injury in the adult brain. We found that intraperitoneal administration of vanadium compounds, a stimulator of phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) pathways markedly enhances the brain ischemia-induced neurogenesis and promotes the migration of newborn cells. Thus, vanadium compounds are potential therapeutic agents to enhance the ischemia-induced neurogenesis through PI3K/Akt and ERK activation.
Shioda
Norifumi
N
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Han
Feng
F
Fukunaga
Kohji
K
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology* / Q000628:therapy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000096:biosynthesis; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000637:transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods; D017968:Vanadium Compounds / Q000627:therapeutic use
D009414:Nerve Growth Factors; D017968:Vanadium Compounds; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases