Brain-Derived Neurotrophic Factor Expression Is Increased in the Hippocampus of 5-HT2C Receptor Knockout Mice
Brain-Derived Neurotrophic Factor Expression Is Increased in the Hippocampus of 5-HT2C Receptor Knockout Mice
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DOI：
10.1002/hipo.20759
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发表时间：
2011-04-01
期刊：
影响因子：
3.5
通讯作者：
van den Buuse, Maarten
中科院分区：
文献类型：
--
作者：
Hill, Rachel A.;Murray, Simon S.;van den Buuse, Maarten
一些研究表明5-HT和BDNF之间存在密切的相互作用;然而，对BDNF和5-HT 2C受体之间的特定关系知之甚少。因此，在这项研究中，我们研究了BDNF的表达在5-HT 2C受体敲除小鼠（5-HT 2CKO）。我们还使用行为测试组合评估了脑源性神经营养因子任何变化的功能后果。Western印迹分析表明，与野生型对照组（WT）相比，5-HT 2CKO小鼠海马中BDNF成熟形式的表达显著增加2.2倍（P = 0.008），但额叶皮质或纹状体没有增加。在5-HT 2CKO组中，未发现BDNF亚型的表达差异，成熟/BDNF亚型的比例显著增加（P = 0.003）。海马BDNF mRNA表达在基因型间无差异。因此，5-HT 2CKO海马中成熟BDNF水平的增加最有可能是由于pro-BDNF向其成熟形式的细胞外裂解速率增加。BDNF受体，原霉素相关受体B（Trk B）的蛋白质表达在海马、额叶皮质和纹状体中也没有变化。在10天的旋转式迷宫任务中，5-HT 2CKO和WT在重复训练后，工作记忆错误和参考记忆错误的数量都有类似的减少。此外，被动或主动回避学习没有观察到基因型特异性差异。5-HT 2CKO表现出适度的运动过度活跃，但在焦虑、感觉运动门控或抑郁样行为测试中没有差异;然而，在尾部悬挂测试中，5-HT 2CKO表现出显著减少的攀爬（P < 0.05）。总之，5-HT 2C受体表达的丧失导致海马中BDNF成熟形式水平的显著和选择性增加。尽管这种显著增加，5-HT 2CKO仅显示出细微的行为变化。(C)2010 Wiley-Liss，Inc.
Several studies have suggested a close interaction between serotonin (5-HT) and BDNF; however, little is known of the specific relationship between BDNF and the 5-HT2C receptor. Therefore, in this study we investigated BDNF expression in 5-HT2C receptor knockout mice (5-HT2CKO). We also assessed functional consequences of any changes in BDNF using a behavioral test battery. Western blot analysis demonstrated a significant 2.2-fold increase in the expression of the mature form of BDNF in 5-HT2CKO mice when compared with wildtype controls (WT) in the hippocampus (P = 0.008), but not frontal cortex or striatum. No differences in the expression of the pro-BDNF isoform were found, and the ratio of mature/pro BDNF was significantly increased in 5-HT2CKO (P = 0.003). BDNF mRNA expression in the hippocampus was not different between the genotypes. Hence, increased mature BDNF levels in 5-HT2CKO hippocampus are most likely due to increased extracellular cleavage rates of pro-BDNF to its mature form. Protein expression of the BDNF receptor, tropomycin-related receptor B (TrkB), was also unchanged in the hippocampus, frontal cortex and striatum. With repeated training in a 10-day win-shift radial arm maze task, 5-HT2CKO and WT showed similar decreases of the number of working memory and reference memory errors. In addition, no genotype specific differences were observed for passive or active avoidance learning. 5-HT2CKO showed modest locomotor hyperactivity but no differences in tests for anxiety, sensorimotor gating, or depressive-like behaviors; however, in the tail suspension test 5-HT2CKO showed significantly reduced climbing (P < 0.05). In conclusion, loss of 5-HT2C receptor expression leads to a marked and selective increase in levels of the mature form of BDNF in the hippocampus. Despite this marked increase, 5-HT2CKO show only subtle behavioral changes. (C) 2010 Wiley-Liss, Inc.