| Budget Amount *help |
¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000)
Fiscal Year 2011: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2010: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2009: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
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| Research Abstract |
Regulatory mechanisms for synaptic transmission should lead to understanding the etiology of brain disorders, such as epilepsy and dementia. So far, we have identified epilepsy-related LGI1 and ADAM22 as the novel ligand/receptor, and showed LGI1 enhances AMPA receptor-mediated synaptic transmission through ADAM22(Fukata et al, Science 2010). To clarify the physiological role of LGI family proteins especially in brain functions, we generated LGI1 knockout(KO) mice and found that LGI1 KO mice showed lethal epileptic phenotype(Fukata et al, PNAS 2010). We found that LGI3 did not bind to ADAM22 and could not rescue LGI1 KO mice, under the condition in which neuronal LGI1 expression could rescue it. Interestingly, LGI4 bound to ADAM22 and partly rescued the epilepsy of LGI1 KO mice. In addition, LGI2 truncation causes a remitting focal epilepsy in dogs(Seppala et al, PLoS Genet 2011). Thus, we found that LGI1, 2, and 4 share their receptors ADAM22 and 23 and regulate the neuronal excitability in different brain regions, while LGI3 may differently function in the brain through the unidentified receptor. Thus, we have made steady and continual progress on clarifying the patho-physiological roles of LGI family in vivo.
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