This study was undertaken to verify the effects of chronic stress and lithium treatments on the hippocampal Na
+,K
+-ATPase activity of rats, as well as to investigate the effects of stress ...interruption and post-stress lithium treatment on this enzyme activity and on spatial memory. Two experiments were carried out; in the first experiment, adult male Wistar rats were divided into two groups: control and submitted to a chronic variate stress paradigm, and subdivided into treated or not with LiCl. After 40 days of treatment, rats were killed, and Na
+,K
+-ATPase activity was determined. In the second experiment, rats were stressed during 40 days, and their performance was evaluated in the Water Maze task. The stressed group was then subdivided into four groups, with continued or interrupted stress treatment and treated or not with lithium for 30 additional days. After a second evaluation of performance in the Water Maze, rats were killed and Na
+,K
+-ATPase activity was also measured. Results showed an impairment in Na
+,K
+-ATPase activity and in Water Maze performance of chronically stressed rats, which were prevented by lithium treatment and reversed by lithium treatment and by stress interruption. These results suggest that the modulation of Na
+,K
+-ATPase activity may be one of the mechanisms of action of lithium in the treatment of mood disorders.
Abstract
Folic acid (FA) supplementation is important during pregnancy to avoid malformations in the offspring. However, it is unknown if it can affect the offspring throughout their lives. To ...evaluate the offspring, female mother rats (dams) were separated into 5 groups: Four groups received the AIN-93 diet, divided into control and FA (5, 10, and 50 mg/kg), and an additional group received a FA-deficient diet, and the diet was performed during pregnancy and lactation. We evaluated the female offspring of these dams (at 2 and 18 months old). The aged offspring fed with FA-deficient diet presented habituation, spatial and aversive memory impairment and the FA maternal supplementation prevented this. The natural aging caused an increase in the TNF-α and IL-1β levels in the hippocampus from 18-month-old offspring. FA maternal supplementation was able to prevent the increase of these cytokines. IL-4 levels decreased in the prefrontal cortex from aged control rats and FA prevented it. FA deficiency decreased the levels of IL-4 in the hippocampus of the young offspring. In addition, natural aging and FA deficiency decreased brain-derived neurotrophic factor levels in the hippocampus and nerve growth factor levels in the prefrontal cortex and FA supplementation prevented it. Thus, the present study shows for the first time the effect of FA maternal supplementation on memory, cytokines, and neurotrophins in the aged offspring.
