Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
Transl Psychiatry. 2022 Mar 7;12(1):93. doi: 10.1038/s41398-022-01858-5.
The common brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety disorders and PTSD. Here we behaviorally phenotyped a novel Val66Met rat model with an equivalent valine to methionine substitution in the rat Bdnf gene (Val68Met). In a three-day fear conditioning protocol of fear learning and extinction, adult rats with the Met/Met genotype demonstrated impaired fear memory compared to Val/Met rats and Val/Val controls, with no genotype differences in fear learning or extinction. This deficit in fear memory occurred irrespective of the sex of the animals and was not seen in adolescence (4 weeks of age). There were no changes in open-field locomotor activity or anxiety measured in the elevated plus maze (EPM) nor in other types of memory measured using the novel-object recognition test or Y-maze. BDNF exon VI expression in the dorsal hippocampus was higher and BDNF protein level in the ventral hippocampus was lower in female Val/Met rats than female Val/Val rats, with no other genotype differences, including in total BDNF, BDNF long, or BDNF IV mRNA. These data suggest a specific role for the BDNF Met/Met genotype in fear memory in rats. Further studies are required to investigate gene-environment interactions in this novel animal model.
常见的脑源性神经营养因子（BDNF）Val66Met 多态性与活性依赖性 BDNF 释放减少和焦虑障碍和 PTSD 风险增加有关。在这里，我们对一种新型的 Val66Met 大鼠模型进行了行为表型分析，该模型在大鼠 Bdnf 基因中具有等效的缬氨酸到蛋氨酸取代（Val68Met）。在为期三天的恐惧条件反射学习和消退协议中，与 Val/Met 大鼠和 Val/Val 对照相比，具有 Met/Met 基因型的成年大鼠表现出恐惧记忆受损，而在恐惧学习或消退中没有基因型差异。这种恐惧记忆缺陷与动物的性别无关，在青春期（4 周龄）时没有出现。在旷场运动活动或高架十字迷宫（EPM）中测量的焦虑方面没有变化，也没有在新颖物体识别测试或 Y 迷宫中测量的其他类型的记忆中出现变化。与 Val/Val 大鼠相比，雌性 Val/Met 大鼠的背侧海马体中的 BDNF exon VI 表达更高，而腹侧海马体中的 BDNF 蛋白水平更低，但其他基因型没有差异，包括总 BDNF、BDNF long 或 BDNF IV mRNA。这些数据表明 BDNF Met/Met 基因型在大鼠的恐惧记忆中具有特定作用。需要进一步研究该新型动物模型中的基因-环境相互作用。
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