Department of Oral Physiology, School of Dentistry & Institute of Oral Bioscience, Jeonbuk National University, Jeonju 54896, Korea.
Int J Mol Sci. 2021 Apr 9;22(8):3908. doi: 10.3390/ijms22083908.
Lithium (Li) salt is widely used as a therapeutic agent for treating neurological and psychiatric disorders. Despite its therapeutic effects on neurological and psychiatric disorders, it can also disturb the neuroendocrine axis in patients under lithium therapy. The hypothalamic area contains GABAergic and glutamatergic neurons and their receptors, which regulate various hypothalamic functions such as the release of neurohormones, control circadian activities. At the neuronal level, several neurotransmitter systems are modulated by lithium exposure. However, the effect of Li on hypothalamic neuron excitability and the precise action mechanism involved in such an effect have not been fully understood yet. Therefore, Li action on hypothalamic neurons was investigated using a whole-cell patch-clamp technique. In hypothalamic neurons, Li increased the GABAergic synaptic activities via action potential independent presynaptic mechanisms. Next, concentration-dependent replacement of Na by Li in artificial cerebrospinal fluid increased frequencies of GABAergic miniature inhibitory postsynaptic currents without altering their amplitudes. Li perfusion induced inward currents in the majority of hypothalamic neurons independent of amino-acids receptor activation. These results suggests that Li treatment can directly affect the hypothalamic region of the brain and regulate the release of various neurohormones involved in synchronizing the neuroendocrine axis.
锂盐被广泛用作治疗神经和精神疾病的治疗剂。尽管它对神经和精神疾病有治疗作用，但它也会干扰锂治疗患者的神经内分泌轴。下丘脑区域包含 GABA 能和谷氨酸能神经元及其受体，它们调节各种下丘脑功能，如神经激素的释放、控制昼夜节律活动。在神经元水平上，几种神经递质系统受锂暴露的调节。然而，锂对下丘脑神经元兴奋性的影响以及这种影响所涉及的确切作用机制尚未完全了解。因此，使用全细胞膜片钳技术研究了锂对下丘脑神经元的作用。在下丘脑神经元中，锂通过动作电位独立的突触前机制增加 GABA 能突触活动。接下来，在人工脑脊液中，浓度依赖性地用 Li 取代 Na 会增加 GABA 能微小抑制性突触后电流的频率，而不改变其幅度。锂灌流诱导大多数下丘脑神经元产生内向电流，而不依赖于氨基酸受体的激活。这些结果表明，锂治疗可以直接影响大脑的下丘脑区域，并调节各种神经激素的释放，这些激素参与同步神经内分泌轴。
