title: Brain polyamine stress response: recurrence after repetitive stressor and inhibition by lithium.
abstract: We recently demonstrated that, unlike in peripheral tissues, the increase in activity of polyamine synthesizing enzymes observed in the brain after acute stress can be prevented by long-term, but not by short-term, treatment with lithium. In the present study we sought to examine the effects of chronic intermittent stress on two key polyamine synthesizing enzymes, ornithine decarboxylase and S-adenosylmethionine decarboxylase, and their modulation by lithium treatment. Adult male rats were subjected to 2 h of restraint stress once daily for 5 days and to an additional delayed stress episode 7 days later. Enzyme activities were assayed 6 h after the beginning of each stress episode. In contrast to the liver, where ornithine decarboxylase activity was increased (300% of the control) only after the first stress episode, the enzyme activity in the brain was increased after each stress episode (to approximately 170% of the control). Unlike ornithine decarboxylase activity, S-adenosylmethionine decarboxylase activity was slightly reduced after the first episode (86% of the control) but remained unchanged thereafter. After cessation of the intermittent stress period, an additional stress episode 7 days later led again to an increase in ornithine decarboxylase activity in the brain (225% of the control) but not in the liver, whereas S-adenosylmethionine decarboxylase activity remained unchanged. The later increase in ornithine decarboxylase activity was blocked by lithium treatment during the intervening 7-day interval between stressors. The results warrant the following conclusions: (a) Repetitive application of stressors results in a recurrent increase in ornithine decarboxylase activity in the brain but to habituation of this response in the liver. (b) This brain polyamine stress response can be blocked by long-term (days) lithium treatment. (c) The study implicates an overreactive polyamine response as a component of the adaptive, or maladaptive, brain response to stressful events and as a novel molecular target for lithium action.
authors.affiliation: Department of Neurology, Tel Aviv Sourasky Medical Center, Israel.
authors.forename: G M
authors.initials: GM
authors.lastname: Gilad
authors.forename: V H
authors.initials: VH
authors.lastname: Gilad
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000517:prevention & control; D013997:Time Factors
chemical_list: D011073:Polyamines; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D018021:Lithium Chloride