Possible involvement of fatty acid binding proteins in psychiatric disorders
Possible involvement of fatty acid binding proteins in psychiatric disorders
复制标题
脂肪酸结合蛋白可能与精神疾病有关
DOI：
10.1007/s12565-020-00598-0
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发表时间：
2021
影响因子：
1.2
通讯作者：
Owada Y
中科院分区：
文献类型：
--
作者：
Yamamoto Y;Owada Y
多不饱和脂肪酸(PUFAs)对大脑发育和功能是必不可少的。越来越多的证据表明，多不饱和脂肪酸的失衡与各种人类精神疾病有关，包括自闭症和精神分裂症。然而，多不饱和脂肪酸在细胞和分子水平上对大脑功能影响的潜在机制仍不清楚。由于多不饱和脂肪酸不溶于水，需要特定的转运体将多不饱和脂肪酸运送到适当的细胞内隔间。脂肪酸结合蛋白(FABP)是多不饱和脂肪酸的细胞伴侣，参与多不饱和脂肪酸的细胞内转运、信号转导和基因转录。因此，我们重点研究了FABP调节的脑内多不饱和脂肪酸稳态与神经元可塑性的关系。作者先前报道，FABP3优先与n-6多不饱和脂肪酸结合，在成年小鼠前扣带回(ACC)的伽马氨基丁酸(GABA)抑制中间神经元中强烈表达，ACC是边缘皮质的组成部分，对认知和情绪行为的协调起重要作用。有趣的是，Fabp3KO小鼠表现出GABA合成增加和ACC兴奋/抑制平衡异常。此外，研究表明，FABP7优先与n-3PUFAs结合，控制星形胶质细胞的脂筏功能，而星形胶质细胞Fabp7缺陷会导致星形胶质细胞对外界刺激的反应改变。此外，Fabp7KO小鼠表现出异常的树突形态，并降低了脊椎密度和锥体神经元的兴奋性突触传递。本文综述了多不饱和脂肪酸或多不饱和脂肪酸结合蛋白与人类精神疾病的关系，并讨论了多不饱和脂肪酸结合蛋白在脑内的功能，尤其是多不饱和脂肪酸结合蛋白3和7在脑中的作用。
Polyunsaturated fatty acids (PUFAs) are essential for brain development and function. Increasing evidence has shown that an imbalance of PUFAs is associated with various human psychiatric disorders, including autism and schizophrenia. However, the mechanisms underlying the effects of PUFAs on brain functions at cellular and molecular levels remain unclear. Since PUFAs are insoluble in water, specific transporters are required to deliver PUFAs to appropriate intracellular compartments. Fatty acid-binding proteins (FABPs), the cellular chaperones of PUFAs, are involved in PUFA intracellular trafficking, signal transduction, and gene transcription. Therefore, we focused on the relationship between FABP-regulated PUFA homeostasis in the brain and neuronal plasticity. The authors previously reported that FABP3, which preferentially binds to n-6 PUFAs, is strongly expressed in the gamma-aminobutyric acid (GABAergic) inhibitory interneurons of the adult mouse anterior cingulate cortex (ACC), which is a component of the limbic cortex and is important for the coordination of cognitive and emotional behaviors. Interestingly,Fabp3KO mice show increased GABA synthesis and abnormal excitatory/inhibitory balance in the ACC. In addition, studies have indicated that FABP7, which preferentially binds to n-3 PUFAs, controls lipid raft function in astrocytes, and astrocyticFabp7deficiency results in an altered response of astrocytes to external stimuli. Furthermore,Fabp7KO mice exhibit aberrant dendritic morphology, and decreased spine density and excitatory synaptic transmission in pyramidal neurons. This review summarizes relationship between PUFAs or FABPs and human psychiatric disorders and discusses recent progress in elucidating the function of FABPs, especially FABP3 and 7, in the brain.