한빛사논문
- 조회3,628
Abstract
Yong-Seok Lee1,2, Dan Ehninger1,7, Miou Zhou1, Jun-Young Oh3, Minkyung Kang2, Chuljung Kwak4, Hyun-Hee Ryu2, Delana Butz5, Toshiyuki Araki6, Ying Cai1, J Balaji1,7, Yoshitake Sano1, Christine I Nam1, Hyong Kyu Kim3, Bong-Kiun Kaang4, Corinna Burger5, Benjamin G Neel6 & Alcino J Silva1
1Integrative Center for Learning and Memory, Departments of Neurobiology, Psychiatry and Biobehavioral Sciences, Psychology and Brain Research Institute, University of California Los Angeles, Los Angeles, California, USA. 2Department of Life Science, Chung-Ang University, Seoul, Korea. 3Department of Medicine and Microbiology, College of Medicine, Signaling Disorder Research Center, Chungbuk National University, Cheongju, Korea. 4School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea. 5Department of Neurology, University of Wisconsin-Madison, Madison, Wisconsin, USA. 6Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. 7Present addresses: DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany (D.E.) and Center for Neuroscience, Indian Institute of Science, Bangalore, India (J.B.).
Correspondence to: Alcino J Silva or Yong-Seok Lee
Abstract
In Noonan syndrome (NS) 30?50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11D61G in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, brief treatment with lovastatin reduces activation of the GTPase Ras-extracellular signal-related kinase (Erk) pathway in the brain and normalizes deficits in LTP and learning in adult Ptpn11D61G/+ mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS.
논문정보
- Research article
- 2014년 11월 (BRIC 등록일 2014-11-14)
- 국내(교신)+국외 연구진
- 생명과학 > 신경생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
