title: Potential roles of Cdk5/p35 and tau protein in hippocampal mossy fiber sprouting in the PTZ kindling model.
abstract: BACKGROUND
  The most well-documented synaptic reorganization associated with temporal lobe epilepsy is mossy fiber sprouting (MFS), which is believed to play a critical role in epileptogenesis. However, the molecular mechanisms underlying this phenomenon remain unclear. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase which is found to be crucial in axon growth and synaptic plasticity. We hypothesized that Cdk5 contributed to MFS via phosphorylating its substrate tau protein, which was known to facilitate microtubule stabilization and axonal elongation.
  
  
  METHODS
  240 male SD rats were randomly divided into the control group and PTZ group. The epileptic models were established by intraperitoneal PTZ injection, while the control rats were injected with an equal dose of saline. At different time points, Cdk5/p35 mRNA and protein, total tau protein and its phosphorylation at Ser202 (p-tau) and Cdk5 activity were analyzed in different regions of hippocampus by in situ hybridization, immunohistochemistry, Western blot, immuno-precipitation and liquid scintillation counter. Hippocampus was also evaluated for MFS with Timm stain.
  
  
  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 expression of Cdk5/p35 mRNA and protein, tau protein and its phosphorylation at Ser202 significantly increased from 3 days to 4 weeks in the PTZ group, which 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 underlying MFS may lead to therapeutic interventions that limit epileptogenesis.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China. tianff@gmail.com
authors.forename: Fa-Fa
authors.initials: FF
authors.lastname: Tian
authors.forename: Chang
authors.initials: C
authors.lastname: Zeng
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Ma
authors.forename: Ting-Hui
authors.initials: TH
authors.lastname: Guo
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: Feng-Rong
authors.initials: FR
authors.lastname: Li
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Wang
authors.forename: Wen-Jiao
authors.initials: WJ
authors.lastname: Huang
authors.forename: Yu-Zhong
authors.initials: YZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D010433:Pentylenetetrazole