P.1.014 Spatial memory and expression levels of BDNF and steroid hormone receptors in the hippocampus of socially isolated offspring

Abstract

Purpose: Rats deprived of social contact with other rats at a young age experience a form of prolonged stress that leads to long-lasting alteration in their behaviour profile. This chronic stress paradigm results in changes of emotional state, hormonal secretion, abnormal reactivity to environmental and pharmacological stimuli and changes in GABAA receptor plasticity and function [1,2]. Moreover, isolated rats, although showed a down-regulation of both brain-derived neurotrophic factor (BDNF) and activityregulated cytoskeletal associated protein (Arc) in the hippocampus, demonstrated an improvement in memory performances in the Morris water maze (MWM) together with an increase in the expression of BDNF and Arc in the hippocampus on both days 1 and 5 and increased plasma level of corticosterone on the 5th day of MWM training [3]. To examine possible trans-generational effects on social isolated offspring we have investigated (1) basal plasma levels of corticosterone, (2) spatial memory performance in the MWM, (3) expression levels of BDNF and Arc in the hippocampus during the 1th and 5th days of MWM. Moreover, in the hippocampus of both isolated and isolated offspring we measured the expression levels of glucocorticoid (GR) and mineralcorticoid (MR) receptors. Methods:Male Sprague-Dawley rats were used. Steroid levels were quantified in plasma by RIA. The levels of BDNF, Arc, GR and MR proteins were determined by Western Blot analysis. The measurement of spatial memory was performed trough the MWM. Data were analyzed by one or two-way ANOVA followed by Newman-Keuls post-hoc test. Results: In social isolated offspring the plasma levels of corticosterone were significantly increased by 31% (p< 0.05) vs group-housed offspring (controls). In the MWM, social isolated offspring showed a decrease in latency to reach the platform during the days of training, and a decrease of the proximity measure to the target zone during the probe trial. Moreover, although the basal levels of hippocampal BDNF and Arc did not differ significantly between the two groups of animals, we found a significant increase of BDNF expression at the 5th day of MWM in isolated offspring vs the control animals (p< 0.05). Finally, the expression of hippocampal GR was significantly augmented in both isolated and isolated offspring (+41%, p< 0.05; +42%, p< 0.05, respectively), while the expression of MR was significantly increased only in the isolated rats (+35%, p< 0.05). Conclusions: Our results suggest that a stressful condition that have been experienced by the parents in early life time influence hormonal secretion, neuronal plasticity and cognitive performances in the offspring. Thus, isolated offspring showed an improvement in learning and spatial memory in MWM vs the control animals. Likewise, high circulating levels of corticosterone with high levels of GR expression in the hippocampus may play an important role in improving the cognitive performance of these animals. These data are in agreement with the increased expression of BDNF since it is involved in various forms of hippocampal learning.