在許多的神經退化性疾病，例如阿茲海默氏症與帕金森氏症，於發病過程中神經性發炎反應和小膠細胞之活化是非常常見的。帕金森氏症主要的病理特徵是位在中腦黑質區之多巴胺神經元選擇性的大量退化。相對來說，身體運動對於大腦有許多的好處，例如，大腦損傷後的保護，尤其是在其後的大腦功能恢復。過去發現到於週邊系統給予脂多醣可以啟動初級免疫反應，接連的於腦內引發小膠細胞之活化和多巴胺神經元退化。跑步運動可以減少脂多醣所引發的多巴胺神經元退化現象。不過，現在仍然不知道其所利用的機制為何。所以，在此假設跑步運動之所以可以保護黑質區的多巴胺神經元對抗脂多醣所引發的神經退化現象是因為以下兩個原因：第一，減少週邊和中樞神經系統中因為脂多醣所引發的發炎反應。第二，增加神經滋養因子而開啟的神經存活訊息傳遞路徑。為了驗證以上的假設，本實驗利用公的八週大 C57BL/6 小鼠進行四週的跑步機運動，隨後腹腔內注射脂多醣。發現到跑步基運動不能減少脂多醣刺激下產生的細胞激素（cytokines） 以及趨化素（chemokines）。跑步機運動-脂多醣處理可以顯著性增加腦神經滋養因子（BDNF）於黑質的表現量，但並不改變神經膠細胞滋養因子（GDNF）的表現量。為了研究跑步機運動的保護作用是否經由 BDNF 及其接受器（TrkB）的訊息傳遞路徑。於跑步機運動後，於側腦室內注射 K252a，Trk B 阻斷劑。 結果顯示阻斷 BDNF-TrkB 的訊息傳遞路徑會消除掉跑步機運動保護多巴胺神經元對抗脂多醣所引發的神經退化現象。再進一步驗證，利用微量滲透壓幫浦直接將 BDNF 注射至紋狀體，也同樣的可以減少脂多醣所引發的多巴胺神經退化現象。總結以上結果，跑步機運動可以保護黑質中的多巴胺神經元對抗週邊內脂多醣引發之傷害，而 BDNF-TrkB 訊息傳遞路徑可能包含在跑步機運動的保護效應中。

Neuroinflammation and microglia activation is a common component of the pathogenesis for multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease (PD). PD is characterized by a progressive and selective degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). On the contrary, physical exercise has beneficial effects on brain function, such as protection after brain damages, especially in terms of recovery of brain function. Previously, the lipopolysaccharide (LPS) administration is known to initiate the innate inflammation response in the periphery which subsequently induces microglia activation and DA neuron degeneration in the brain. Running exercise has been shown to reduce LPS-induced DA neuron degeneration. However, the underlying mechanism remains unclear. Therefore, I hypothesize that running exercise protecting DA neuron against LPS-induced degeneration in SN is due to 1) reducing peripheral LPS-induced CNS inflammatory responses, and 2) increasing the neurotrophic pro-survival signaling pathways. To test these hypotheses, 8-week-old C57BL/6 male mice were subjected to a 4-week treadmill running (TR) exercise followed by an intraperitoneal injection of LPS; TR did not reduce the levels of LPS-stimulated cytokines and chemokines in the SN. The levels of the brain-derived neurotrophic factor (BDNF) but not the glial cell derived neurotrophic factor (GDNF) were reduced by LPS treatment and TR significantly enhanced the expression of BDNF. To investigate the effect of BDNF-TrkB pathway on the TR-induced protection, K252a, a Trk B antagonist, was intracerebroventricular injected after four weeks of TR. The results showed that inhibition of BDNF-TrkB pathway abolished the TR-induced protection against LPS-induced DA neuron degeneration. Furthermore, intrastriatal perfused with BDNF with osmotic pump also reduced the LPS-induced DA neuron degeneration. Taken together, TR is able to protect DA neuron in SN against peripheral LPS-induced injury. The BDNF-TrkB signaling is involved in the TR-induced protection.

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