AGE-RELATED-CHANGES BY HYPOXIA AND TRH ANALOG ON SYNAPTIC ATPASE ACTIVITIES

Some synaptosomal energy-requiring ATPases were evaluated in the cerebral cortex from 3- and 24-month-old normoxic rats and rats submitted to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or TRH analogue posatireline was performed. The activities of Na+,K+-ATPase, low- and high-affinity Ca2+-ATPase, Mg2+-ATPase, and Ca2+,Mg2+-ATPase were assayed in synaptosomes and synaptosomal subfractions, namely synaptosomal plasma membranes and synaptic vesicles. With the exception of the high-affinity Ca2+-ATPase, aging induced a decrease in the ATPase activities from normoxic rats. The adaptation to chronic intermittent mild hypoxia was characterized by an increase in the activity of Mg2+-ATPase in 3-month-old rats, concomitant with a decrease in the activities of: a) Na+,K+-ATPase and high-affinity Ca2+-ATPase in both 3- and 24-month-old rats, and b) Ca2+,Mg2+-ATPase in 3-month-old ones. The TRH analogue posatireline increased the high-affinity Ca2+-ATPase in both 3- and 24-month-old hypoxic rats, concomitant with an increase in Mg2+-ATPase activity in 24-month-old ones. The adaptation to chronic intermittent severe hypoxia was characterized by a decrease in the activities of: a) Na+,K+-ATPase, Ca2+,Mg2+-ATPase and high-affinity Ca2+-ATPase in both 3- and 24-month-old rats, and b) low-affinity Ca2+-ATPase only in 24-month-old ones. The effect on Mg2+-ATPase activity was characterized by a decrease in the enzymatic form located in the synaptic plasma membranes, concomitant with an increase in the form located in the synaptic vesicles. In both 3- and 24-month-old hypoxic rats, TRH analogue increased the activity of the Na+,K+-ATPase and the enzymatic form of the Mg2+-ATPase located in the synaptosomal plasma membranes, concomitant with a decrease in the form of the Mg2+-ATPase located in the synaptic vesicles.