Enriched Environment Experience Overcomes Learning Deficits and Depressive-Like Behavior Induced by Juvenile Stress

Mood disorders affect the lives and functioning of millions each year. Epidemiological studies indicate that childhood trauma is predominantly associated with higher rates of both mood and anxiety disorders. Exposure of rats to stress during juvenility (JS) (27–29 days of age) has comparable effects and was suggested as a model of induced predisposition for these disorders. The importance of the environment in the regulation of brain, behavior and physiology has long been recognized in biological, social and medical sciences. Here, we studied the effects of JS on emotional and cognitive aspects of depressive-like behavior in adulthood, on Hypothalamic-Pituitary-Adrenal (HPA) axis reactivity and on the expression of cell adhesion molecule L1 (L1-CAM). Furthermore, we combined it with the examination of potential reversibility by enriched environment (EE) of JS – induced disturbances of emotional and cognitive aspects of behavior in adulthood. Three groups were tested: Juvenile Stress –subjected to Juvenile stress; Enriched Environment – subjected to Juvenile stress and then, from day 30 on to EE; and Naïves. In adulthood, coping and stress responses were examined using the elevated plus-maze, open field, novel setting exploration and two way shuttle avoidance learning. We found that, JS rats showed anxiety- and depressive-like behaviors in adulthood, altered HPA axis activity and altered L1-CAM expression. Increased expression of L1-CAM was evident among JS rats in the basolateral amygdala (BLA) and Thalamus (TL). Furthermore, we found that EE could reverse most of the effects of Juvenile stress, both at the behavioral, endocrine and at the biochemical levels. The interaction between JS and EE resulted in an increased expression of L1-CAM in dorsal cornu ammonis (CA) area 1 (dCA1)

Enriched Environment Experience Overcomes Learning Deficits and Depressive-Like Behavior Induced by Juvenile Stress

Mood disorders affect the lives and functioning of millions each year. Epidemiological studies indicate that childhood trauma is predominantly associated with higher rates of both mood and anxiety disorders. Exposure of rats to stress during juvenility (JS) (27–29 days of age) has comparable effects and was suggested as a model of induced predisposition for these disorders. The importance of the environment in the regulation of brain, behavior and physiology has long been recognized in biological, social and medical sciences. Here, we studied the effects of JS on emotional and cognitive aspects of depressive-like behavior in adulthood, on Hypothalamic-Pituitary-Adrenal (HPA) axis reactivity and on the expression of cell adhesion molecule L1 (L1-CAM). Furthermore, we combined it with the examination of potential reversibility by enriched environment (EE) of JS – induced disturbances of emotional and cognitive aspects of behavior in adulthood. Three groups were tested: Juvenile Stress –subjected to Juvenile stress; Enriched Environment – subjected to Juvenile stress and then, from day 30 on to EE; and Naïves. In adulthood, coping and stress responses were examined using the elevated plus-maze, open field, novel setting exploration and two way shuttle avoidance learning. We found that, JS rats showed anxiety- and depressive-like behaviors in adulthood, altered HPA axis activity and altered L1-CAM expression. Increased expression of L1-CAM was evident among JS rats in the basolateral amygdala (BLA) and Thalamus (TL). Furthermore, we found that EE could reverse most of the effects of Juvenile stress, both at the behavioral, endocrine and at the biochemical levels. The interaction between JS and EE resulted in an increased expression of L1-CAM in dorsal cornu ammonis (CA) area 1 (dCA1)

Open Field (OF) Test.

<p>(A) <i>Time spent in the open arena</i>. Time spent in the open arena of the OF of the JS (n = 17) group was significantly shorter than that of the Naïve (n = 20) and JS+EE (n = 17) groups. Time spent in the open arena of the JS+EE group was significantly longer than that of the Naïves and JS. Time spent in the open arena of the Naïve group was significantly longer than that of the JS, while being significantly shorter than that of the JS+EE group. (B) <i>The locomotor activity in the OF</i>. The number of center square crossing of the JS group was significantly lower than that of the Naïve and JS+EE groups. The number of center square crossing of the JS+EE group was significantly higher than that of the Naïves and JS. The number of center square crossing of the Naïve group was significantly higher than that of the JS, while being significantly lower than that of the JS+EE group. There was no difference between the groups in the number of periphery square crossing and total locomotor activity (total number of squares crossed) in the OF. *significantly different from all other groups (p<0.05).</p

Two-Way Shuttle (TWS) Avoidance learning.

<p>(A) <i>Avoidance responses</i>. Percent of avoidance responses of the JS+EE (n = 8) group was significantly higher than that of the Naïve (n = 10) and JS (n = 8) groups. (B) <i>Escape responses</i>. Percent of escape responses of the JS+EE group was significantly lower than that of the Naïve and JS groups. (C) <i>No Escape responses</i>. Percent of no escape responses of the JS group was significantly higher than that of the Naïve and JS+EE groups. *significantly different from all other groups (p<0.05); #significantly different from Naïve group (p<0.05).</p

Elevated Plus Maze (EPM).

<p>(A) <i>Time spent in the open arms</i>. Time spent in the open arms of the JS (n = 29) group was significantly shorter than that of the Naïve (n = 31) and JS+EE (n = 30) groups. There was no significant difference between JS+EE and Naïve groups. (B) <i>The locomotor activity in the EPM</i>. The line crossing in the open arms of the JS group was significantly lower than that of the JS+EE group. Line crossing in the closed arms of the JS+EE group was significantly higher than that of the Naïve and JS groups. Total line crossing of the JS+EE group was significantly higher than that of the Naïve and JS groups. *significantly different from all other groups (p<0.05); &significantly different from JS+EE group (p<0.05); #significantly different from Naïve group (p<0.05).</p

Exploration of a novel setting.

<p>Exploratory behavior of the JS (n = 38) group was significantly lower than that of the Naïve (n = 41) and JS+EE (n = 40) groups. The exploratory behavior of the JS+EE group was significantly higher than that of the Naïves and JS. The exploratory behavior of the Naïve group was significantly higher than that of the JS, while being significantly lower than that of the JS+EE group. *significantly different from all other groups (p<0.05).</p

L1-CAM expression at post natal day 60.

<p>(A) L1-CAM expression was measured at 60 PND in the PFC, BLA, dCA1 and TL (Naïve (n = 10); JS+EE (n = 8); JS+EE (n = 8)). Expression levels are depicted as the ratio between the total L1-CAM expression level and β-actin levels in each brain area (i.e. L1-CAM/β-actin), normalized to the Naïve group. <u>In the PFC</u>: no difference between the groups for L1-CAM expression levels. <u>In the BLA</u>: L1-CAM expression levels of the JS group was significantly higher than that of the Naïve group. <u>In the dCA1</u>: L1-CAM expression levels of the JS+EE group was significantly higher than that of the Naïve group. <u>In the TL</u>: L1-CAM expression levels of the JS group was significantly higher than that of the Naïve and JS+EE groups. (B) L1-CAM representative immunoblots. Bottom rows: β-actin; Top Rows: L1-CAM. *significantly different from all other groups (p<0.05); #significantly different from Naïve group (p<0.05).</p

Serum corticosterone concentration.

<p>Basal CORT concentration of the JS (n = 9) group was significantly higher than that of the Naïve (n = 10) and JS+EE (n = 8) groups. *significantly different from all other groups (p<0.05).</p

Body weight.

<p>JS (n = 39) and JS+EE (n = 39) exhibited less body weight gain when examined 24 h after the exposure to stress compared to Naïve group (n = 48). However, one week later (38 PND) this difference was observed only for the JS group. There was no difference between Naïve and JS+EE groups. Later on during the maturation process (at 45, 52, and 59 PND), this difference was no longer evident. *JS significantly different from Naïve (p<0.05); #JS+EE significantly different from Naïve (p<0.05).</p

Accuracy Improvement in Magnetic Field Modeling for an Axisymmetric Electromagnet

This paper examines the accuracy and calculation speed for the magnetic field computation in an axisymmetric electromagnet. Different numerical techniques, based on an adaptive nonuniform grid, high order finite difference approximations, and semi-analitical calculation of boundary conditions are considered. These techniques are being applied to the modeling of the Variable Specific Impulse Magnetoplasma Rocket. For high-accuracy calculations, a fourth-order scheme offers dramatic advantages over a second order scheme. For complex physical configurations of interest in plasma propulsion, a second-order scheme with nonuniform mesh gives the best results. Also, the relative advantages of various methods are described when the speed of computation is an important consideration