Hong Namgue, Park Jeong-Soo, Kim Hee Jung
Department of Physiology, College of Medicine, Dankook University, Cheonan, Republic of Korea.
Department of Medical Laser, Graduate School, Dankook University, Cheonan, Republic of Korea.
Anim Cells Syst (Seoul). 2021 Dec 27;26(1):1-9. doi: 10.1080/19768354.2021.2018044. eCollection 2022.
Human immunodeficiency virus type I (HIV-1) infection of the CNS produces synapse loss which correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). Lithium is mood stabilizer of unknown mechanism used to treat bipolar disorder and is known to exhibit neuroprotective properties. Here, we studied the effects of lithium on HIV-1 Tat-induced synapses between rat hippocampal neurons. The number of synapses was quantified to detect clusters of the scaffold protein postsynaptic density 95 (PSD95) which is clustered at glutamatergic synapses on cultured rat hippocampal neurons . Lithium protected synapses from HIV-1 Tat-induced synapse loss and subsequent neuronal death. This synaptic protection was prevented by both the activation of NMDA receptor leading to intracellular signaling and the regulatory pathway of lithium including inositol depletion and glycogen synthase kinase-3 (GSK-3). These results suggest that mood stabilizers might be effective drugs to treat neurodegenerative disorders including HAND.
I型人类免疫缺陷病毒（HIV-1）感染中枢神经系统会导致突触丧失，这与HIV相关神经认知障碍（HAND）患者的认知衰退相关。锂是一种作用机制不明的情绪稳定剂，用于治疗双相情感障碍，已知具有神经保护特性。在此，我们研究了锂对HIV-1反式激活蛋白（Tat）诱导的大鼠海马神经元之间突触的影响。通过对支架蛋白突触后致密物95（PSD95）的簇进行定量来检测突触数量，PSD95聚集在培养的大鼠海马神经元的谷氨酸能突触上。锂可保护突触免受HIV-1 Tat诱导的突触丧失及随后的神经元死亡。通过激活NMDA受体导致细胞内信号传导以及锂的调节途径（包括肌醇耗竭和糖原合酶激酶-3（GSK-3））均可阻止这种突触保护作用。这些结果表明，情绪稳定剂可能是治疗包括HAND在内的神经退行性疾病的有效药物。
