Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally

Experimental Neurology
Zaodung LingPaul M Carvey

Abstract

Toxin-induced animal models of Parkinson's disease (PD) exhibit many of the same neuroinflammatory changes seen in patients suggesting a role for inflammation in DA neuron loss. Yet, despite this inflammation, the progressive loss of DA neurons that characterizes PD is rarely seen in animals. We infused lipopolysaccharide (LPS) or saline into 7-month-old rats that had been exposed to LPS or saline prenatally and assessed them for DA neuron loss and inflammatory measures (interleukin 1 beta, tumor necrosis factor-alpha, glutathione, and activated microglia) over a period of 84 days to examine the role of pre-existing inflammation in progressive DA neuron loss. LPS infusion into both prenatal treatment groups produced neuroinflammation during the 14 days of LPS infusion that subsequently reverted toward normal over the next 70 days. In animals with pre-existing inflammation (i.e., prenatal LPS), however, the acute changes seen were attenuated, but took much longer to return to normal suggesting a prolonged inflammatory response. These inflammatory changes were consistent with the greater acute DA neuron loss seen in the prenatal saline controls and the progressive DA neuron loss seen only in the animals exposed to LPS prenatally....Continue Reading

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