title: [Neuronal death mode switch and neurogenesis as in vivo neuroprotection].
abstract: The brain has various in vivo neuroprotective mechanisms that allow it to survive for an entire lifetime. As well as neurotrophic factor-mediated inhibition of in vivo apoptotic mechanisms through various protein kinases including Akt and MAP kinase, we propose adding the neuronal death mode switch mechanism observed under the brain ischemic stress to the list of neuroprotective mechanisms. Necrosis occurs when energy or ATP levels are markedly reduced. Lowered ATP levels cause a Na(+)-K(+)-ATPase failure, leading to an osmolysis. On the other hand, sufficient ATP is required for the apoptosome activation. Under the serum-free condition, cortical neurons rapidly die in necrosis. High-glucose treatment converted the cell death mode to apoptosis through an elevation of cellular ATP levels. This treatment also rescued the cell from death due to retinal ischemic injury. These findings suggest the possibility that ischemia-induced neuronal death could be inhibited by some drugs to elevate cellular ATP levels. Neurogenesis in the adult brain is now an important topic in neuroscience. As brain injury is reported to enhance the neurogenesis, this might be also included in the ways of in vivo neuroprotection. As lysophosphatidic acid has various activities to drive neurogenesis, the neurogenesis could also be managed by other drugs to compensate for functions lost by neuronal death.
authors.affiliation: Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Nagasaki 852-8521, Japan. ueda@net.nagasaki-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.forename: Wakako
authors.initials: W
authors.lastname: Hamabe
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology
chemical_list: D000255:Adenosine Triphosphate; D011494:Protein Kinases