Mechanism and treatment for the learning and memory deficit in mouse models of Noonan syndrome > 세미나

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Mechanism and treatment for the learning and memory deficit in mouse m…

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  • 2014-04-23

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[2014 Spring Life Sciences & IBB Regular Seminar] 


 


  


▶Subject: Mechanism and treatment for the learning and memory deficit in mouse models of Noonan syndrome


     


 


▶Speaker: Yong-Seok Lee, Ph.D. (Chung-Ang University)


      


 


▶Date: 4:00PM/April/25(Fri)/2014


     


  


▶Place: Auditorium(1F), Postech Biotech Center


     


 


    *Abctract


     Noonan syndrome (NS) is an autosomal dominant genetic disorder affecting 1 in 2,500 live births and 30% to 50% of NS patients show cognitive deficits. Mutations in the Ptpn11 gene, which up-regulate Ras-ERK signaling, account for ~50% of NS. Here, we report that heterozygous knock-in mice expressing NS-associated gain-of-function Ptpn11 mutations (Ptpn11D61G/+ and Ptpn11N308D/+) show hippocampal-dependent spatial learning impairments caused by deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of the PTPN11D61G gene, specifically in adult hippocampus, results in increases in basal levels of ERK activity, changes in excitation, deficits in hippocampal CA1 LTP and consequently in spatial learning impairments, demonstrating that deregulation of Ptpn11 function and associated LTP deficits specifically in adult CA fields are sufficient to cause spatial learning deficits. Accordingly, a MEK inhibitor SL327 can reverse the LTP and learning deficits caused by the Ptpn11D61G mutation. Moreover, we show that a brief treatment with an FDA approved drug, lovastatin, which reduces Ras-ERK activation in the brain, rescues both the LTP and learning deficits in adult Ptpn11D61G/+ mice under the condition that lovastatin does not affect the wild type controls. Our results demonstrate that increases in basal levels of ERK activity and corresponding impairments in LTP are responsible for the learning deficits in mouse models of NS. Furthermore, these data suggest that lovastatin may be used in treating the cognitive deficits in NS.



 


 ▶Inquiry: Prof.Kim, Joung-Hun (279-2347)


    


 


 * This seminar will be given in English




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