Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Neurotoxicology. 2021 Jul;85:254-264. doi: 10.1016/j.neuro.2021.05.015. Epub 2021 Jun 13.
Parkinson's disease (PD) is the second most common neurodegenerative disease, characterised by the loss of dopaminergic neurons in the substantia nigra. Mounting evidence indicates a crucial role of inflammation and concomitant oxidative stress in the disease progression. Therefore, the aim of this study was to investigate the ability of systemically administered lipopolysaccharide (LPS) to induce motor and non-motor symptoms of PD, inflammation, oxidative stress and major neuropathological hallmarks of the disease in regions postulated to be affected, including the olfactory bulb, hippocampus, midbrain and cerebellum. Twenty-one male C57BL/6 mice, approximately 20 weeks old, received a dose of 0.3 mg/kg/day of LPS systemically on 4 consecutive days and behavioural testing was conducted on days 14-18 post-treatment, followed by tissue collection. Systemically administered LPS increased latency time in the buried food seeking test (indicative of olfactory impairment), and decreased time spent in central zone of the open field (anxiety-like behaviour). However, there was no change in latency time in the rotarod test or the expression of tyrosine hydroxylase (TH) in the midbrain. Systemically administered LPS induced increased glial markers GFAP and Iba-1 and oxidative stress marker 3-nitrotyrosine (3-NT) in the olfactory bulb, hippocampus, midbrain and cerebellum, and there were region specific changes in the expression of NFκB, IL-1β, α-synuclein, TH and BDNF proteins. The model could be useful to further elucidate early non-motor aspects of PD and the possible mechanisms contributing to the non-motor deficits.
帕金森病（PD）是第二常见的神经退行性疾病，其特征是黑质中多巴胺能神经元的丧失。越来越多的证据表明炎症和随之而来的氧化应激在疾病进展中起着至关重要的作用。因此，本研究旨在研究全身性给予脂多糖（LPS）是否能诱导 PD 的运动和非运动症状、炎症、氧化应激以及假定受影响的疾病的主要神经病理学特征，包括嗅球、海马体、中脑和小脑。21 只大约 20 周龄的雄性 C57BL/6 小鼠连续 4 天每天接受 0.3mg/kg 的 LPS 全身给药，治疗后第 14-18 天进行行为测试，然后收集组织。全身性给予 LPS 增加了埋藏食物寻找测试中的潜伏期（表明嗅觉受损），并减少了旷场测试中的中央区时间（焦虑样行为）。然而，在旋转棒测试或中脑酪氨酸羟化酶（TH）的表达中没有潜伏期的变化。全身性给予 LPS 诱导了嗅球、海马体、中脑和小脑中神经胶质标志物 GFAP 和 Iba-1 以及氧化应激标志物 3-硝基酪氨酸（3-NT）的增加，并且 NFκB、IL-1β、α-突触核蛋白、TH 和 BDNF 蛋白的表达也有特定的区域变化。该模型可用于进一步阐明 PD 的早期非运动方面以及可能导致非运动缺陷的机制。
