Vollmayr B, Faust H, Lewicka S, Henn F A
Central Institute of Mental Health, J5, D-68159 Mannheim, Germany.
Mol Psychiatry. 2001 Jul;6(4):471-4, 358. doi: 10.1038/sj.mp.4000907.
Stress-induced elevation of glucocorticoids is accompanied by structural changes and neuronal damage in certain brain areas. This includes reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus which can be prevented by chronic electroconvulsive seizures and antidepressant drug treatment. In the last years we have bred two strains of rats, one which reacts with congenital helplessness to stress (cLH), and one which congenitally does not acquire helplessness when stressed (cNLH). After being selectively bred for more than 40 generations these strains have lost their behavioural plasticity including their sensitivity to antidepressant treatment. We show here that in cLH rats, acute immobilization stress does not induce a reduction of BDNF expression in the hippocampus which is observed in Sprague--Dawley and cNLH rats. All animals tested exhibited elevated corticosterone levels when stressed, an indication, that in cLH rats regulation of BDNF expression in the hippocampal formation is uncoupled from corticosterone increase induced through stress. This may explain the lack of adaptive responses in this strain.
应激诱导的糖皮质激素升高伴随着某些脑区的结构变化和神经元损伤。这包括海马体中脑源性神经营养因子(BDNF)表达的降低,而慢性电惊厥发作和抗抑郁药物治疗可以预防这种情况。在过去几年中,我们培育了两种品系的大鼠,一种对应激产生先天性无助反应(cLH),另一种在应激时先天性不会产生无助感(cNLH)。经过40多代的选择性培育,这些品系已经失去了行为可塑性,包括对抗抑郁治疗的敏感性。我们在此表明,在cLH大鼠中,急性固定应激不会像在斯普拉格-道利大鼠和cNLH大鼠中那样诱导海马体中BDNF表达的降低。所有接受测试的动物在应激时皮质酮水平都会升高,这表明在cLH大鼠中,海马结构中BDNF表达的调节与应激诱导的皮质酮增加脱钩。这可能解释了该品系缺乏适应性反应的原因。