Cabral Laís M, Oliveira Luiz M, Miranda Nicole C, Kawamoto Elisa M, K P Costa Soraia, Moreira Thiago S, Takakura Ana C
Department of Pharmacology, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP 05508-000, Brazil.
Department of Physiology and Biophysics, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, SP 05508-000, Brazil.
Brain Res. 2024 Jan 1;1822:148586. doi: 10.1016/j.brainres.2023.148586. Epub 2023 Sep 25.
Parkinson's Disease (PD) is characterized by classic motor symptoms related to movement, but PD patients can experience symptoms associated with impaired autonomic function, such as respiratory disturbances. Functional respiratory deficits are known to be associated with brainstem neurodegeneration in the mice model of PD induced by 6-hydroxydopamine (6-OHDA). Understanding the causes of neuronal death is essential for identifying specific targets to prevent degeneration. Many mechanisms can explain why neurons die in PD, and neuroinflammation is one of them. To test the influence of inflammation, mediated by microglia and astrocytes cells, in the respiratory disturbances associated with brainstem neurons death, we submitted wild-type (WT) and TNF receptor 1 (TNFR1) knockout male mice to the 6-OHDA model of PD. Also, male C57BL/6 animals were induced using the same PD model and treated with minocycline (45 mg/kg), a tetracycline antibiotic with anti-inflammatory properties. We show that degeneration of brainstem areas such as the retrotrapezoid nucleus (RTN) and the pre-Botzinger Complex (preBotC) were prevented in both protocols. Notably, respiratory disturbances were no longer observed in the animals where inflammation was suppressed. Thus, the data demonstrate that inflammation is responsible for the breathing impairment in the 6-OHDA-induced PD mouse model.
帕金森病（PD）的特征是与运动相关的典型运动症状，但PD患者可能会出现与自主神经功能受损相关的症状，如呼吸紊乱。已知在6-羟基多巴胺（6-OHDA）诱导的PD小鼠模型中，功能性呼吸缺陷与脑干神经变性有关。了解神经元死亡的原因对于确定预防变性的特定靶点至关重要。许多机制可以解释PD中神经元为何死亡，神经炎症就是其中之一。为了测试由小胶质细胞和星形胶质细胞介导的炎症对与脑干神经元死亡相关的呼吸紊乱的影响，我们将野生型（WT）和肿瘤坏死因子受体1（TNFR1）基因敲除雄性小鼠用于6-OHDA诱导的PD模型。此外，使用相同的PD模型诱导雄性C57BL/6动物，并给予米诺环素（45mg/kg）治疗，米诺环素是一种具有抗炎特性的四环素抗生素。我们发现，在两种方案中，诸如后梯形核（RTN）和前包钦格复合体（preBotC）等脑干区域的变性均得到了预防。值得注意的是，在炎症受到抑制的动物中不再观察到呼吸紊乱。因此，数据表明炎症是6-OHDA诱导的PD小鼠模型中呼吸障碍的原因。
