OBJECTIVE: To determine CSF eicosanoid concentrations and brain cyclo-oxygenase activity in AD patients and age-matched control subjects. BACKGROUND: Nonsteroidal anti-inflammatory drugs may benefit AD patients by inhibiting cyclo-oxygenases and thereby reducing prostaglandin (PG) production or oxidant stress in the CNS. METHODS: CSF eicosanoid and F2-isoprostane (IsoP) levels were determined in seven probable AD patients and seven age-matched control subjects. Cyclo-oxygenase activity was determined in microsomes prepared from the hippocampus of 10 definite AD patients and 8 age-matched control subjects. All measurements were made using gas chromatography/mass spectrometry. RESULTS: CSF concentrations of prostaglandin (PG) E2 were increased fivefold (p < 0.01) and 6-keto-PGF1alpha was decreased fourfold (p < 0.01) in probable AD patients. There was no change in total CSF eicosanoid concentration in probable AD patients. CSF F2-IsoP, a quantitative marker of lipid peroxidation in vivo, was increased in probable AD patients (p < 0.05). Cyclo-oxygenase activity in the hippocampus from definite AD patients was not different from age-matched control subjects. CONCLUSIONS: These data suggest that cyclo-oxygenase activity may not contribute significantly to CNS oxidative damage in AD. Increased CSF PGE2 concentration in probable AD patients suggest that cyclo-oxygenase inhibitors may benefit AD patients by limiting PG production.
OBJECTIVE: To determine CSF eicosanoid concentrations and brain cyclo-oxygenase activity in ADpatients and age-matched control subjects. BACKGROUND: Nonsteroidal anti-inflammatory drugs may benefit ADpatients by inhibiting cyclo-oxygenases and thereby reducing prostaglandin (PG) production or oxidant stress in the CNS. METHODS: CSF eicosanoid and F2-isoprostane (IsoP) levels were determined in seven probable ADpatients and seven age-matched control subjects. Cyclo-oxygenase activity was determined in microsomes prepared from the hippocampus of 10 definite ADpatients and 8 age-matched control subjects. All measurements were made using gas chromatography/mass spectrometry. RESULTS: CSF concentrations of prostaglandin (PG) E2 were increased fivefold (p < 0.01) and 6-keto-PGF1alpha was decreased fourfold (p < 0.01) in probable ADpatients. There was no change in total CSF eicosanoid concentration in probable ADpatients. CSF F2-IsoP, a quantitative marker of lipid peroxidation in vivo, was increased in probable ADpatients (p < 0.05). Cyclo-oxygenase activity in the hippocampus from definite ADpatients was not different from age-matched control subjects. CONCLUSIONS: These data suggest that cyclo-oxygenase activity may not contribute significantly to CNS oxidative damage in AD. Increased CSF PGE2 concentration in probable ADpatients suggest that cyclo-oxygenase inhibitors may benefit ADpatients by limiting PG production.
Authors: Xiongwei Zhu; Hyoung-Gon Lee; Gemma Casadesus; Jesus Avila; Kelly Drew; George Perry; Mark A Smith Journal: Mol Neurobiol Date: 2005 Impact factor: 5.590
Authors: Jenny U Johansson; Nathaniel S Woodling; Qian Wang; Maharshi Panchal; Xibin Liang; Angel Trueba-Saiz; Holden D Brown; Siddhita D Mhatre; Taylor Loui; Katrin I Andreasson Journal: J Clin Invest Date: 2014-12-08 Impact factor: 14.808
Authors: Nathaniel S Woodling; Damien Colas; Qian Wang; Paras Minhas; Maharshi Panchal; Xibin Liang; Siddhita D Mhatre; Holden Brown; Novie Ko; Irene Zagol-Ikapitte; Marieke van der Hart; Taline V Khroyan; Bayarsaikhan Chuluun; Prachi G Priyam; Ginger L Milne; Arash Rassoulpour; Olivier Boutaud; Amy B Manning-Boğ; H Craig Heller; Katrin I Andreasson Journal: Brain Date: 2016-05-13 Impact factor: 13.501