Department of Organ Anatomy, Tohoku University, Seiryo-machi Aoba-ku, Sendai, 980-8575, Japan.
Department of Anatomy, Tohoku Medical and Pharmaceutical University, Fukumuro Miyagino-ku, Sendai, 980-8578, Japan.
Anat Sci Int. 2021 Jun;96(3):333-342. doi: 10.1007/s12565-020-00598-0. Epub 2021 Feb 18.
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, Fabp3 KO 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 astrocytic Fabp7 deficiency results in an altered response of astrocytes to external stimuli. Furthermore, Fabp7 KO 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.
多不饱和脂肪酸（PUFAs）对大脑发育和功能至关重要。越来越多的证据表明，PUFAs 的不平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，PUFAs 对细胞和分子水平大脑功能的影响的机制尚不清楚。由于 PUFAs 不溶于水，因此需要特定的转运体将 PUFAs 输送到适当的细胞内隔室。脂肪酸结合蛋白（FABP）是 PUFAs 的细胞伴侣，参与 PUFAs 的细胞内运输、信号转导和基因转录。因此，我们专注于 FABP 调节的大脑中 PUFAs 动态平衡与神经元可塑性之间的关系。作者先前报道，优先结合 n-6 PUFAs 的 FABP3 在成年小鼠前扣带皮层（ACC）的γ-氨基丁酸（GABAergic）抑制性中间神经元中强烈表达，ACC 是边缘皮层的一部分，对于协调认知和情绪行为很重要。有趣的是，Fabp3 KO 小鼠在 ACC 中表现出 GABA 合成增加和兴奋性/抑制性平衡异常。此外，研究表明，优先结合 n-3 PUFAs 的 FABP7 控制星形胶质细胞中的脂筏功能，并且星形胶质细胞 Fabp7 缺乏导致星形胶质细胞对外界刺激的反应改变。此外，Fabp7 KO 小鼠表现出异常的树突形态，以及锥体神经元中的棘密度和兴奋性突触传递减少。这篇综述总结了 PUFAs 或 FABPs 与人类精神疾病的关系，并讨论了阐明 FABPs，特别是 FABP3 和 7 在大脑中的功能的最新进展。
