Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene
Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene
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DOI：
10.1111/j.1460-9568.2006.04855.x
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Kondo, Hisatake
中科院分区：
文献类型：
--
作者：
Owada, Yuji;Abdelwahab, Soha Abdelkawi;Kondo, Hisatake
脑型脂肪酸结合蛋白（B-FABP）属于细胞内脂质结合蛋白家族。B-FABP对长链脂肪酸（FAs）表现出结合亲和力，其对脑功能包括发育、情绪、学习和记忆的影响已被提出。B-FABP定位于啮齿类动物胚胎脑的心室胚细胞和发育和成熟脑的星形胶质细胞。在本研究中，我们产生的小鼠窝藏在B-FABP基因无效突变，并研究其表型。B-FABP突变小鼠在新生期表现出焦虑增强和恐惧记忆增加，以及大脑中二十二碳六烯酸（DHA）含量降低，但未检测到任何脑组织学变化。在成人脑中，B-FABP更多地定位于杏仁核和隔区的星形胶质细胞，而不是海马区。成年小鼠大脑杏仁核中FA含量的分析表明，与野生型相比，突变小鼠的花生四烯酸和棕榈酸显着增加。此外，与野生型相比，B-FABP突变体脑神经元的N-甲基-d-天冬氨酸受体介导电流对DHA的反应显著降低，而与空间学习记忆相关的行为反应和海马长时程增强无显著差异。这些数据表明，B-FABP是至关重要的参与恐惧记忆和焦虑，通过其与脂肪酸的结合和/或其自身的相关代谢/信号的脂肪酸的直接影响。
Brain-type fatty acid-binding protein (B-FABP) belongs to a family of intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long-chain fatty acids (FAs) whose effects on brain functions including development, emotion, learning and memory have been proposed. B-FABP is localized in the ventricular germinal cells in embryonic brain and astrocytes in developing and mature brain of rodents. In the present study we generated the mouse harboring a null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice exhibited the enhanced anxiety and increased fear memory as well as the decreased content of docosahexaenoic acid (DHA) in their brain during the neonatal period without detection of any histological changes in the brain. In the adult brain, B-FABP was localized more numerously to the astrocytes in the amygdala and septal area than to those in the hippocampal area. Analysis of FA content in the amygdala of adult brain revealed that arachidonic and palmitic acids increased significantly in the mutant mice compared with wild-type. Furthermore, the response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated neurons from B-FABP mutant brain was significantly decreased compared with that of wild-type, while no significant differences were detected in behavioral responses related to the spatial learning/memory or in the hippocampal long-term potentiation. These data indicate that B-FABP is crucially involved in the fear memory and anxiety through its binding with FAs and/or its own direct effects on pertinent metabolism/signaling of FAs.