Ilchibaeva Tatiana V, Tsybko Anton S, Kozhemyakina Rimma V, Kondaurova Elena M, Popova Nina K, Naumenko Vladimir S
The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of Russian Academy of Sciences, Lavrentyeva av.10, Novosibirsk, 630090, Russia.
The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of Russian Academy of Sciences, Lavrentyeva av.10, Novosibirsk, 630090, Russia.
Behav Brain Res. 2018 May 2;343:102-110. doi: 10.1016/j.bbr.2018.01.034. Epub 2018 Feb 6.
Brain-derived neurotrophic factor (BDNF), its precursor proBDNF, BDNF pro-peptide, BDNF mRNA levels, as well as TrkB and p75 receptors mRNA and protein levels, were studied in the brain of rats, selectively bred for more than 85 generations for either the high level or the lack of fear-induced aggressive behavior. Furthermore, we have found that rats of aggressive strain demonstrated both high level of aggression toward humans and increased amplitude of acoustic startle response compared to rats selectively bred for the lack of fear-induced aggression. Significant increase in the BDNF mRNA, mature BDNF and proBDNF protein levels in the raphe nuclei (RN), hippocampus (Hc), nucleus accumbens (NAcc), amygdala, striatum and hypothalamus (Ht) of aggressive rats was revealed. The BDNF/proBDNF ratio was significantly reduced in the Hc and NAcc of highly aggressive rats suggesting prevalence of the proBDNF in these structures. In the Hc and frontal cortex (FC) of aggressive rats, the level of the full-length TrkB (TrkB-FL) receptor form was decreased, whereas the truncated TrkB (TrkB-T) protein level was increased in the RN, FC, substantia nigra and Ht. The TrkB-FL/TrkB-T ratio was significantly decreased in highly aggressive rats suggesting TrkB-T is predominant in highly aggressive rats. The p75 expression was slightly changed in majority of studied brain structures of aggressive rats. The data indicate the BDNF system in the brain of aggressive and nonaggressive animals is extremely different at all levels, from transcription to reception, suggesting significant role of BDNF system in the development of highly aggressive phenotype.
在经过85代以上选择性培育，分别具有高水平或缺乏恐惧诱导攻击行为的大鼠大脑中，研究了脑源性神经营养因子（BDNF）、其前体proBDNF、BDNF前肽、BDNF mRNA水平，以及TrkB和p75受体的mRNA和蛋白质水平。此外，我们发现，与因缺乏恐惧诱导攻击行为而选择性培育的大鼠相比，攻击品系的大鼠对人类表现出高水平的攻击性，且听觉惊吓反应幅度增加。研究发现，攻击型大鼠的中缝核（RN）、海马体（Hc）、伏隔核（NAcc）、杏仁核、纹状体和下丘脑（Ht）中，BDNF mRNA、成熟BDNF和proBDNF蛋白水平显著增加。高攻击性大鼠的Hc和NAcc中BDNF/proBDNF比值显著降低，表明这些结构中proBDNF占优势。在攻击型大鼠的Hc和额叶皮质（FC）中，全长TrkB（TrkB-FL）受体形式的水平降低，而截断的TrkB（TrkB-T）蛋白水平在RN、FC、黑质和Ht中增加。高攻击性大鼠中TrkB-FL/TrkB-T比值显著降低，表明TrkB-T在高攻击性大鼠中占主导地位。在攻击型大鼠的大多数研究脑结构中，p75表达略有变化。数据表明，攻击性和非攻击性动物大脑中的BDNF系统在从转录到受体的各个水平上都存在极大差异，这表明BDNF系统在高度攻击性表型的发展中起重要作用。
