Division of Molecular Pharmacology and Neuroscience
Nagasaki University Graduate School of Biomedical Sciences
Nagasaki University Center for Pain Research
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Theme 1
Molecular and Cellular Biology of Neuronal Protection
1. Topics
We are interested in total sciences of neuroprotection of adult brain. They include the mechanisms through novel factors secreted from neurons and glial cells upon injury or ischemic stress. We are also interested in neurogenesis regulated by biologically active factors, such as lysophosphatidic acid. Our goal is to identify novel molecular targets to search for new medicines.

2. Recent Discoveries
When brain neurons were cultured in the absence of serum or any supplements, they rapidly die in a mode of necrosis under the low-density condition, while relatively slowly die in a mode of apoptosis under the high-density condition (Fujita et al. (2001) Cell. Mol. Neurobiol. 21(4), 317-324). Recently we found that conditioned medium factors from high-density culture switched the necrosis to apoptosis through an action of protein kinase C (Fujita R. and UEDA H. Cell Death and Differentiation; 10(12) 1336-1347, 2003). High glucose treatments also switched through similar but not identical mechanisms (Fujita R and UEDA H, Cell Death and Differentiation; 10(7);782-790, 2003). Most recently, we demonstrated that insulin mediates inhibition of neuronal necrosis through a novel mechanism involving PKC-gamma activation (Hamabe et al., JPET, 2005).

3. Methodologies/Technologies
Necrosis and apoptosis are clearly characterized by use of TEM, SEM and many molecular probes including Annexin V, activated caspase antibodies, cytochrome c release, TUNEL and propidium iodide. Mouse brain and retinal ischemia/reperfusion models. Electroporation of specific genes and RNAi. Various viral gene transfer using adenovirus and retrovirus for in vivo and in vitro studies. Protein purification and MALDI-TOF-TOF system for protein sequencing. Yeast two hybrid system and gene screening from retrovirus library. Behavioral studies for memory/learning.