Antidepressant-like effect of n-3 PUFAs in CUMS rats: role of tPA/PAI-1 system
Antidepressant-like effect of n-3 PUFAs in CUMS rats: role of tPA/PAI-1 system
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DOI：
10.1016/j.physbeh.2014.11.054
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发表时间：
2015-02
影响因子：
2.9
通讯作者：
Mimi Tang;Pei Jiang;Huande Li;H. Cai;Yiping Liu;H. Gong;Lihong Zhang
中科院分区：
文献类型：
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作者：
Mimi Tang;Pei Jiang;Huande Li;H. Cai;Yiping Liu;H. Gong;Lihong Zhang
脑源性神经营养因子与抑郁症的发展密切相关。最近的证据表明，组织型纤溶酶原激活物（tPA）和纤溶酶原激活物抑制剂-1（派-1）与前脑源性神经营养因子（BDNF）裂解成其成熟形式有关。慢性轻度应激（Chronic unpredicted mild stress，CIMS）是一种广泛应用于啮齿类动物的抑郁行为诱导方法。因此，我们研究了PUFAs和舍曲林对Wistar大鼠tPA/派-1系统的影响。经过5周的BVS程序后，大鼠被诱导至抑郁样状态。派-1和proBDNF在海马和前额叶皮质的表达增加。N-3多不饱和脂肪酸（PUFAs）或舍曲林可逆转行为学改变，并诱导tPA在某些脑区的表达，但不能恢复LPS诱导的派-1表达。同时，抗抑郁药治疗也加速了proBDNF向成熟BDNF的细胞外转化。本研究首次揭示了抑郁症大鼠前额叶皮层和海马tPA/派-1系统的同步平衡改变，PUFAs和舍曲林可部分改善这种平衡，为tPA/派-1系统参与抑郁症的发生发展和治疗提供了新的证据。
BDNF is strongly implicated in the development of depression. Recent evidence has indicated that tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) are related to the cleavage of pro-brain-derived neurotrophic factor (BDNF) into its mature form. Chronic unpredicted mild stress (CUMS) is widely used to induce depressive behaviors in rodents. Therefore, we investigated the effects of PUFAs and sertraline on tPA/PAI-1 system in CUMS rats. After 5 weeks of CUMS procedures, the rats were induced to a depressive-like state. The expressions of PAI-1 and proBDNF were increased in the prefrontal cortex and hippocampus of CUMS rats. N-3 polyunsaturated fatty acids (PUFAs) or sertraline administration reversed the changes in behavioral test and induced the expression of tPA in certain brain areas, but failed to restore the CUMS-induced PAI-1 expression. Meanwhile, the antidepressant treatment also accelerated the extracellular conversion of proBDNF into mature BDNF in CUMS rats. Our results firstly showed the synchronously altered balance of tPA/PAI-1 system in the prefrontal cortex and hippocampus of CUMS rats, which was partly ameliorated by PUFAs and sertraline medication, providing new evidence for the involvement of tPA/PAI-1 system in the progression and treatment of depression.