title: [Involvement of Cdk5/p35 and tau protein in the hippocampal mossy fiber sprouting in the PTZ kindling model].
abstract: OBJECTIVE
  To observe the expression of cyclin-dependent kinase 5 (Cdk5), p35, tau protein and the activity of Cdk5 in rat hippocampus during pentylenetetrazole (PTZ) kindling process and their correlation with mossy fiber sprouting (MFS) so as to investigate the role of Cdk5/p35 in epileptogenesis.
  
  
  METHODS
  A total of 240 healthy male SD rats were divided randomly into normal controls and pentylenetetrazole (PTZ) treatment groups. The epileptic models were established by injection of PTZ intraperitoneally. At Day 3, Weeks 1, 2, 4 & 6 after a daily injection of PTZ, Timm staining was scored in the CA3 region and dentate gyrus. At the same time, the mRNA and protein of Cdk5 and p35, total tau protein and its phosphorylation at ser202 and Cdk5 activity were analyzed in the hilus and stratum granulosum of dentate gyrus and the CA1, CA3 regions of hippocampus. The methods of in situ hybridization, immunohistochemistry, Western blot and immuno-precipitation and liquid scintillation counter were employed respectively.
  
  
  RESULTS
  Prominent MFS was observed in area CA3 rather than the inner molecular layer in PTZ-treated rats. And the degree of MFS progressed with the development of behavioral kindled seizures. The expressions of Cdk5/p35 mRNA and protein, tau protein and its phosphorylation at Ser202 significantly increased from Day 3 to Week 4 in the PTZ treatment group. It was in accordance with the progression of MFS in area CA3.
  
  
  CONCLUSIONS
  Cdk5/p35 and its substrate tau protein may be involved in MFS. Understanding the molecular mechanisms of MFS may lead to therapeutic interventions for limiting epileptogenesis.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China. tianff@mail.csu.edu.cn
authors.forename: Fa-fa
authors.initials: FF
authors.lastname: Tian
authors.forename: Ting-hui
authors.initials: TH
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Dang
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Ma
authors.forename: Jin-mei
authors.initials: JM
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Cai
authors.forename: Ming-yu
authors.initials: MY
authors.lastname: Song
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004195:Disease Models, Animal; D007696:Kindling, Neurologic / Q000378:metabolism*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D010433:Pentylenetetrazole