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

• Published in: Pharmacology, biochemistry and behavior Vol. 91; no. 3; pp. 339 - 344
• Main Authors: El-faramawy, Yasser A., El-banouby, Mohamed H., Sergeev, Pavel, Mortagy, Ahmed K., Amer, Motassem S., Abdel-tawab, Ahmed M.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 2009; Elsevier
• Subjects: 7-nitroindazole; Aging - physiology; Animals; Biological and medical sciences; Blotting, Western; Chromatography, High Pressure Liquid; Chronic Disease; Chronic mild stress; Enzyme Inhibitors - pharmacology; Feeding Behavior - drug effects; gamma-Aminobutyric Acid - metabolism; Glutamate Decarboxylase - metabolism; Glutamate decarboxylase enzyme; Glutamic Acid - metabolism; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Indazoles - pharmacology; Male; Medical sciences; Neuroprotective Agents - pharmacology; Nitric Oxide Synthase Type I - antagonists & inhibitors; Old rats; Phosphorylation; Rats; Rats, Wistar; Stress, Psychological - metabolism; tau Proteins - metabolism; tau-protein phosphorylation; 7-nitroindazole; Chronic mild stress; tau-protein phosphorylation; Glutamate decarboxylase enzyme; Old rats; Hippocampus; Phosphorylation; Rat; Nitric oxide synthase inhibitor; Central nervous system; Lyases; Encephalon; Enzymatic activity; Carboxy-lyases; Enzyme; Rodentia; Glutamate decarboxylase; Stress; Carbon-carbon lyases; Vertebrata; Chronic; Mammalia; Tau protein; Animal; Reversibility
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2008.08.003

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 µmol/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 µmol/g tissue protein;
p
=
0.0005), and decreased phosphorylation of
tau proteins compared to CMS exposed rats.