Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio CU, Col. San Manuel, 72570, Puebla, Mexico.
Unidad Periférica de Neurociencias, Facultad de Medicina, Universidad Nacional Autónoma de México, Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Ciudad de Mexico, Mexico.
Neurotox Res. 2020 Jan;37(1):1-11. doi: 10.1007/s12640-019-00104-z. Epub 2019 Sep 2.
Parkinson's disease (PD) is an idiopathic and progressive neurodegenerative disease characterized by the loss of ~ 80% of dopaminergic neurons in substantia nigra pars compacta (SNpc). Because activation of the innate cellular immune response, mediated by microglia, has been linked to the neurodegeneration in PD, in the present study, we evaluated the effects of lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) on microglia's morphology, reflective of their activity, as well as tyrosine hydroxylase (TH)-positive neurons in SNpc and motor behavior. Adult male Wistar rats were stereotactically injected with LPS or 6-OHDA into the left dorsolateral striatum. Control groups received appropriate vehicle. The morphological changes of microglial cells and neurotoxic effects were examined at 1, 7, and 14 post-injection days. Both LPS and 6-OHDA caused activation and morphological changes in microglial cells as well as loss of dopaminergic neurons in SNpc. These effects were maximal at 14 days post-injection where motor impairments were also evident. However, our findings indicate that 6-OHDA causes a low degree of microglia activation compared to LPS. Hence, it may be concluded that LPS model of PD might be a better representation of inflammatory involvement in this devastating disease.
帕金森病（PD）是一种特发性、进行性神经退行性疾病，其特征是黑质致密部（SNpc）中约 80%的多巴胺能神经元丧失。由于小胶质细胞介导的固有细胞免疫反应的激活与 PD 中的神经退行性变有关，因此在本研究中，我们评估了脂多糖（LPS）和 6-羟多巴胺（6-OHDA）对 SNpc 中微胶质细胞形态的影响，微胶质细胞的形态反映了其活性，以及酪氨酸羟化酶（TH）阳性神经元和运动行为。成年雄性 Wistar 大鼠被立体定向注射 LPS 或 6-OHDA 到左侧背外侧纹状体。对照组接受适当的载体。在注射后 1、7 和 14 天检查小胶质细胞的形态变化和神经毒性作用。LPS 和 6-OHDA 均导致 SNpc 中微胶质细胞的激活和形态变化以及多巴胺能神经元的丧失。这些作用在注射后 14 天达到最大，此时也出现了运动障碍。然而，我们的研究结果表明，与 LPS 相比，6-OHDA 引起的小胶质细胞激活程度较低。因此，可以得出结论，LPS 诱导的 PD 模型可能更好地代表了炎症在这种毁灭性疾病中的参与。
