title: Small interfering RNA directed against CTMP reduces acute traumatic brain injury in a mouse model by activating Akt.
abstract: OBJECTIVE
  Protein kinase B (PKB/Akt), which is phosphorylated and activated by upstream activators, exerts critical neuroprotective effects by phosphorylating downstream targets after traumatic brain injury (TBI). Studies on the regulation of Akt will be crucial for our understanding of neuronal survival. The goal of this study is to investigate the effects of carboxyl-terminal modulator protein (CTMP) on phosphorylation of Akt and neurological function in a mouse model of TBI.
  
  
  METHODS
  Traumatic brain injury in mice was performed by a controlled cortical impact device. The expression of Akt, phospho-Akt, and CTMP was examined in the injured cortices by immunohistochemistry and Western blot analysis. To determine the effects of CTMP, small interfering RNAs (siRNAs) directed against CTMP were injected in mice with TBI, and the expression of phosphorylated Akt and neurological function were evaluated.
  
  
  RESULTS
  Phospho-Akt significantly increased at 4 hours post-TBI in the nucleus (P < 0.01) and remained at high levels until 72 hours after TBI, as shown by Western blot analysis. In the cytosol, the expression of phospho-Akt reached its peak at 4 hours post-TBI, but decreased markedly at 24 hours and maintained below pre-TBI levels until 72 hours post-TBI. Interestingly, the expression of CTMP significantly increased 4 hours after TBI (P < 0.01) and sustained those levels until 72 hours without dramatic changes. Treatment with CTMP siRNA effectively augmented the phosphorylation of Akt and significantly improved the neurological functional recovery up to 28 days post-TBI.
  
  
  CONCLUSIONS
  We conclude that Akt is phosphorylated and translocated to nucleus after TBI to exert neuroprotective effects. However, CTMP is simultaneously triggered to inhibit the phosphorylation of Akt. Inhibition of CTMP by siRNA improves the recovery of neurological functions after TBI.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Zhao
authors.forename: Jidi
authors.initials: J
authors.lastname: Fu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Radhika
authors.initials: R
authors.lastname: Rastogi
authors.forename: Jialiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics*; D020127:Recovery of Function; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: C541471:CTMP protein, rat; D002352:Carrier Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt,; CTMP siRNA,; CTMP,; Nuclear translocation,; Traumatic brain injury