Journal of Neuroimmune Pharmacology ( IF 5.2 ) Pub Date : 2024-03-02 , DOI: 10.1007/s11481-024-10112-2
Joanna Ewa Sowa 1 , Krzysztof Tokarski 1 , Grzegorz Hess 1
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Primarily regarded as immune proteins, chemokines are emerging as a family of molecules serving neuromodulatory functions in the developing and adult brain. Among them, CXCL12 is constitutively and widely expressed in the CNS, where it was shown to act on cellular, synaptic, network, and behavioral levels. Its receptor, CXCR4, is abundant in the amygdala, a brain structure involved in pathophysiology of anxiety disorders. Dysregulation of CXCL12/CXCR4 signaling has been implicated in anxiety-related behaviors. Here we demonstrate that exogenous CXCL12 at 2 nM but not at 5 nM increased neuronal excitability in the lateral division of the rat central amygdala (CeL) which was evident in the Late-Firing but not Regular-Spiking neurons. These effects were blocked by AMD3100, a CXCR4 antagonist. Moreover, CXCL12 increased the excitability of the neurons of the basolateral amygdala (BLA) that is known to project to the CeL. However, CXCL12 increased neither the spontaneous excitatory nor spontaneous inhibitory synaptic transmission in the CeL. In summary, the data reveal specific activation of Late-Firing CeL cells along with BLA neurons by CXCL12 and suggest that this chemokine may alter information processing by the amygdala that likely contributes to anxiety and fear conditioning.
Graphical Abstract
中文翻译：
趋化因子 CXCL12 激活 CXCR4 受体可增加大鼠中枢杏仁核神经元的兴奋性
趋化因子主要被视为免疫蛋白，正在成为在发育中的大脑和成人大脑中发挥神经调节功能的分子家族。其中，CXCL12 在 CNS 中组成型和广泛表达，在 CNS 中被证明它作用于细胞、突触、网络和行为水平。它的受体 CXCR4 在杏仁核中含量丰富，杏仁核是参与焦虑症病理生理学的大脑结构。CXCL12/CXCR4 信号转导失调与焦虑相关行为有关。在这里，我们证明 2 nM 而不是 5 nM 的外源性 CXCL12 增加了大鼠中枢杏仁核 （CeL） 外侧分裂的神经元兴奋性，这在晚发神经元中很明显，但在规则尖峰神经元中并不明显。这些作用被 CXCR4 拮抗剂 AMD3100 阻断。此外，CXCL12 增加了已知投射到 CeL 的基底外侧杏仁核 （BLA） 神经元的兴奋性。然而，CXCL12 既没有增加 CeL 中的自发性兴奋性突触传递，也没有增加自发性抑制性突触传递。总之，数据揭示了 CXCL12 对 Late-Firing CeL 细胞和 BLA 神经元的特异性激活，并表明这种趋化因子可能会改变杏仁核的信息处理，这可能会导致焦虑和恐惧条件反射。
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