Parkinson’s disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characterized by motor dysfunction. While PD symptoms are well treated with L-DOPA, continuous use can cause L-DOPA-induced dyskinesia (LID). We have previously demonstrated that sub-anesthetic ketamine attenuated LID development in rodents, measured by abnormal involuntary movements (AIMs), and reduced the density of maladaptive striatal dendritic mushroom spines. Microglia may play a role by phagocytosing maladaptive neuronal spines. In this exploratory study, we hypothesized that ketamine would prevent AIMs and change microglia ramified morphology – an indicator of a microglia response. Unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats were primed with daily injections of L-DOPA for 14 days, treated on days 0 and 7 for 10-hours with sub-anesthetic ketamine (i.p.), and we replicated that this attenuated LID development. We further extended our prior work by showing that while ketamine treatment did lead to an increase of striatal interleukin-6 in dyskinetic rats, indicating a modulation of an inflammatory response, it did not change microglia number or morphology in the dyskinetic striatum. Yet an increase of CD68 in the SNpc of 6-OHDA-lesioned hemispheres post-ketamine indicates increased microglia phagocytosis suggestive of a lingering microglial response to 6-OHDA injury in the SNpc pointing to possible anti-inflammatory action in the PD model in addition to anti-dyskinetic action. In conclusion, we provide further support for sub-anesthetic ketamine treatment of LID. The mechanisms of action for ketamine, specifically related to inflammation and microglia phagocytic functions, are emerging, and require further examination.

帕金森病 (PD) 是一种神经退行性疾病，由黑质致密部 (SNpc) 中的多巴胺能神经元死亡引起，以运动功能障碍为特征。虽然使用 L-DOPA 可以很好地治疗 PD 症状，但持续使用会导致 L-DOPA 诱发的运动障碍 (LID)。我们之前已经证明，亚麻醉剂氯胺酮减弱了啮齿动物 LID 的发展，通过异常不自主运动 (AIM) 测量，并降低了适应不良的纹状体树突状蘑菇刺的密度。小胶质细胞可能通过吞噬适应不良的神经元棘发挥作用。在这项探索性研究中，我们假设氯胺酮会预防 AIM 并改变小胶质细胞的分支形态——小胶质细胞反应的一个指标。单侧 6-羟基多巴胺 (6-OHDA) 损伤的大鼠每天注射 L-DOPA 14 天，知识产权), 我们复制了这减弱了 LID 的发展。我们进一步扩展了我们之前的工作，表明虽然氯胺酮治疗确实导致运动障碍大鼠纹状体白细胞介素 6 增加，表明炎症反应得到调节，但它并没有改变运动障碍纹状体中的小胶质细胞数量或形态。然而，氯胺酮后 6-OHDA 损伤半球的 SNpc 中 CD68 的增加表明小胶质细胞吞噬作用增加，表明小胶质细胞对 SNpc 中的 6-OHDA 损伤有持续的反应，这表明 PD 模型中除了抗运动障碍作用。总之，我们为 LID 的亚麻醉氯胺酮治疗提供了进一步的支持。氯胺酮的作用机制，特别是与炎症和小胶质细胞吞噬功能相关的机制正在出现，