title: Analysis of neuronal cell death in the cerebral cortex of H-Tx rats with compensated hydrocephalus.
abstract: OBJECTIVE
  Some cases of compensatory hydrocephalus have been reported in which cognitive deficiency progresses despite the absence of progressive ventricular dilation. In this study, the differentially expressed genes in compensated hydrocephalic H-Tx rat cortices were determined. A molecular mechanism that induces neuronal death in the cerebral cortex of compensated hydrocephalus is proposed.
  
  
  METHODS
  The cerebral cortices of 8-week-old H-Tx rats with spontaneously arrested hydrocephalus (hH-Tx) and nonhydrocephalic H-Tx (nH-Tx) control rats were subjected to cDNA microarray analysis followed by canonical pathway analysis.
  
  
  RESULTS
  In the hH-Tx rats, many genes in the amyloidal processing pathway showed altered expression, including Akt3 and p38 MAPK. These latter genes are involved in tau protein phosphorylation, and their increased expression in hydrocephalus was confirmed by real-time polymerase chain reaction analysis. Immunohistological and immunoblot analysis revealed elevated phosphorylated tau expression in the cerebral cortex neurons of the hH-Tx rats.
  
  
  CONCLUSIONS
  The accumulation of phosphorylated tau protein in the cerebral cortex may be one of the mechanisms by which later cognitive dysfunction develops in patients with compensated hydrocephalus. More work needs to be done to determine if the accumulation of phosphorylated tau in the cortex can help predict which patients may decompensate thus requiring more aggressive treatment for compensated hydrocephalus.
authors: Department of Neurosurgery and Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Tokyo, Japan. nona@med.juntendo.ac.jp
authors: Yasuomi
authors: Y
authors: Nonaka
authors: Masakazu
authors: M
authors: Miyajima
authors: Ikuko
authors: I
authors: Ogino
authors: Madoka
authors: M
authors: Nakajima
authors: Hajime
authors: H
authors: Arai
mesh_terms: D000818:Animals; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000453:epidemiology; D004277:DNA, Single-Stranded; D006850:Hydrocephalus, Normal Pressure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D016875:tau Proteins; C111490:Akt3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases