Takayama Chitoshi, Yafuso Tsukasa
Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, Kiyuna 1076, Ginowan, Okinawa, 9012720, Japan.
Anat Sci Int. 2025 Jul 9. doi: 10.1007/s12565-025-00869-8.
In the mature central nervous system (CNS), γ-aminobutyric acid (GABA) and glycine (Gly) are predominant inhibitory neurotransmitters that negatively regulate neural activities. In contrast, GABA mediates membrane potential depolarization during development, and GABA/Gly become excitatory after nerve injury because of the high intracellular Cl concentration induced by low expression of K, Cl cotransporter 2 (KCC2), which transports Cl out of neurons. Many studies have reported that during CNS development, GABAergic excitatory action might play crucial roles in neurogenesis through Ca influx. Nevertheless, its involvement in neurogenesis has not been proven because the CNS can develop normally without GABAergic signals. Recently, two research groups demonstrated that low level of KCC2 (i.e., GABA/Gly excitation) after nerve injury is involved in axonal regeneration and in enhancement of functional recovery. In this manuscript, we review GABA/Gly excitation and introduce recent findings describing its involvement in axonal regeneration.
在成熟的中枢神经系统（CNS）中，γ-氨基丁酸（GABA）和甘氨酸（Gly）是主要的抑制性神经递质，它们对神经活动起负向调节作用。相比之下，GABA在发育过程中介导膜电位去极化，并且由于钾氯共转运体2（KCC2，其将氯离子转运出神经元）低表达导致细胞内氯离子浓度升高，神经损伤后GABA/甘氨酸会变为兴奋性递质。许多研究报道，在中枢神经系统发育过程中，GABA能兴奋性作用可能通过钙离子内流在神经发生中起关键作用。然而，其在神经发生中的作用尚未得到证实，因为中枢神经系统在没有GABA能信号的情况下也能正常发育。最近，两个研究小组证明，神经损伤后低水平的KCC2（即GABA/甘氨酸兴奋）参与轴突再生和功能恢复的增强。在本手稿中，我们综述了GABA/甘氨酸兴奋作用，并介绍了描述其参与轴突再生的最新研究结果。
