DEVELOPMENTAL REGULATION OF THE BRAIN POLYAMINE-STRESS-RESPONSE

A transient increase in brain polyamine metabolism termed the polyamin e-stress-response is a common response to stressful stimuli. Previous studies have implicated an over-reactive polyamine response as a compo nent of the maladaptive brain response to stressful events, and as a n ovel molecular mechanism involved in the pathophysiology of affective disorders. Ample evidence indicates that stressful experiences during early life can alter normal developmental processes and may result in pathophysiological and behavioral changes in the adult. Additionally, an important characteristic of affective disorders is their age depend ency, a phenomenon that may be correlated with a maladaptive regulatio n of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine sy stem. In the present study we measured the activities of the enzymes o rnithine decarboxylase and S-adenosylmethionine decarboxylase as marke rs of polyamine synthesis and found that unlike adults, immature rats do not show the characteristic brain polyamine-stress-response. Instea d of the characteristic increase observed in adults, ornithine decarbo xylase activity in immature animals was reduced or remained unchanged (for up to 16 days of age) after a dexamethasone injection or restrain t stress application. The ontogenesis of this ornithine decarboxylase response was brain region-specific, indicating its dependence on the s tage of neuronal maturation. Animals treated with dexamethasone at 7 d ays of age, showed increased behavioral reactivity in the open-held te st as adults and an attenuated increase in ornithine decarboxylase act ivity after a re-challenge with dexamethasone at age 60 days. The resu lts indicate that: (1) the brain polyamine-stress-response is developm entally regulated and its ontogenesis is brain region-specific, indica ting dependence on the stage of neuronal maturation; (2) the switch to a mature polyamine-stress-response pattern coincides with the cessati on of the stress hyporesponsive period in the HPA system: (3) activati on of the polyamine-stress-response, as in the mature brain, appears t o be a constructive reaction, while its down-regulation, as in the dev eloping brain, may be implicated in neuronal cell death; (4) an attenu ated dexamethasone-induced increase in ornithine decarboxylase activit y implicates an altered polyamine-stress-response in the maladaptive r esponse of the brain to stressful events. (C) 1998 ISDN. Published by Elsevier Science Ltd.