title: Changes in glutamate decarboxylase enzyme activity and tau-protein phosphorylation in the hippocampus of old rats exposed to chronic mild stress: reversal with the neuronal nitric oxide synthase inhibitor 7-nitroindazole.
abstract: Effects of chronic stress are not completely understood. They may underlie depression and dementia. This study assessed the association between chronic stress, glutamate levels, tau-protein phosphorylation, and nitric-oxide in old rats exposed to chronic mild stress (CMS). Old (>15 months) male Wistar rats were exposed to CMS. Comparison groups included old and young control rats, young CMS-exposed, and old CMS-exposed rats treated with the neuronal nitric-oxide synthase (nNOS) enzyme inhibitor, 7-nitroindazole (20 mg/kg/day i.p.). Hippocampal glutamate levels and glutamate decarboxylase (GAD) activity were determined and tau protein phosphorylation was assessed. Age was a significant (p=0.025) source of variation in glutamate level [811.71+/-218.1, 665.9+/-124.9 micromol/g tissue protein (M+/-SD) in young and old control rats, respectively]. Old rats exposed to CMS were characterized by an increased risk to develop anhedonia. There was significant (p=0.035) decrease in GAD enzyme activity (-60.06%) and increased tau protein hyperphosphorylation in old rats exposed to CMS compared to control. Administration of 7-nitroindazole to CMS-exposed old rats significantly (p=0.002) increased GAD activity, decreased glutamate levels (7.19+/-3.19 vs. 763.9+/-91 micromol/g tissue protein; p=0.0005), and decreased phosphorylation of tau proteins compared to CMS exposed rats.
authors.affiliation: Department of Geriatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Yasser A
authors.initials: YA
authors.lastname: El-faramawy
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: El-banouby
authors.forename: Pavel
authors.initials: P
authors.lastname: Sergeev
authors.forename: Ahmed K
authors.initials: AK
authors.lastname: Mortagy
authors.forename: Motassem S
authors.initials: MS
authors.lastname: Amer
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abdel-tawab