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

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 (CAD) 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 mu mol/g tissue protein (M +/- SD) in Young and old control rats, respectively]. Old rats exposed to CMS were characterized by all increased risk to develop anhedonia. There was significant (p=0.035) decrease in CAD 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 mu mol/g tissue protein; p=0.0005), and decreased phosphorylation of tau proteins compared to CMS exposed rats. (c) 2008 Elsevier Inc. All rights reserved.