Study the protective effects of exercise against LPS-induced dopaminergic neuron degerneration

• Main Authors: Tzu-FengWang, 王姿丰
• Other Authors: Yu-Min Kuo
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/37925645025890736357

碩士 === 國立成功大學 === 細胞生物及解剖學研究所 === 98 === 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.