Li Ying, Ji Yong-juan, Jiang Hong, Liu De-xiang, Zhang Qian, Fan Shu-jian, Pan Fang
Institute of Medical Psychology, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
Chin Med J (Engl). 2009 Jul 5;122(13):1564-9.
Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats.
Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry.
Age and stress had different effects on the behavior of different aged animals (age: F = 6.173, P < 0.05, stress: F = 6.056, P < 0.05). Stress was the main factor affecting sucrose preference (F = 123.608, P < 0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P < 0.05). The older stress rats showed a lower sucrose preference than young stress rats (P < 0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P < 0.05), exhibiting fewer vertical movements (P < 0.05) and less grooming (P < 0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups (P < 0.05), a reduction that was still present at the eighth day after stress (P < 0.05). Stress and age were the main factors affecting the expression of BDNF (F = 9.408, P < 0.05; F = 106.303, P < 0.05). The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point.
Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.
脑源性神经营养因子（BDNF）是一种应激反应性细胞间信使，可调节下丘脑 - 垂体 - 肾上腺（HPA）轴的活性。目前，应激与年龄在BDNF表达中的相互作用尚未完全明确。本研究旨在观察不可预测应激对不同年龄大鼠海马CA3亚区（CA3）和齿状回中行为及BDNF表达的影响。
将48只不同年龄（2个月和15个月）的Wistar大鼠随机分为六组：两个对照组和四个应激组。应激组大鼠接受为期三周的不可预测轻度应激。通过蔗糖偏好试验和旷场试验中的探究行为观察来确定动物的抑郁状态和应激水平。采用免疫组织化学法检测海马CA3和齿状回中BDNF的表达。
年龄和应激对不同年龄动物的行为有不同影响（年龄：F = 6.173，P < 0.05；应激：F = 6.056，P < 0.05）。应激是影响蔗糖偏好的主要因素（F = 123.608，P < 0.05）。应激后直接出现蔗糖偏好降低和行为抑制，在年轻动物中至少持续到应激后第八天（P < 0.05）。老年应激大鼠的蔗糖偏好低于年轻应激大鼠（P < 0.05）。老年对照大鼠在旷场试验中的行为与年轻对照动物不同，在中央广场停留时间更长（P < 0.05），垂直运动更少（P < 0.05），理毛行为更少（P < 0.05）。暴露于应激后，老年大鼠的垂直运动和理毛行为无明显变化。这表明老年大鼠在应激期前处于非兴奋状态，对应激刺激的反应比年轻大鼠小。两个年龄组在应激后海马CA3和齿状回区域的BDNF表达均显著降低（P < 0.05），这种降低在应激后第八天仍然存在（P < 0.05）。应激和年龄是影响BDNF表达的主要因素（F = 9.408，P < 0.05；F = 106.303，P < 0.05）。在每个测试时间点，老年应激组的BDNF表达均低于年轻应激组。
应激对大鼠的行为反应和海马BDNF表达具有年龄依赖性影响。
