n-3 polyunsaturated fatty acids inhibit lipopolysaccharide-induced microglial activation and dopaminergic injury in rats

Increasing evidence indicates that neuroinflammation plays an important role in neurotoxins-induced neurodegenerations. Microglia are a type of glial cells in the brain and play as the first and main form of active immune defense in the central nervous system. Accumulated data suggest that the activation of microglia plays a critical role in neurotoxicities induced by environmental toxicants. So the inhibition of microglia has been proven to be an effective strategy against neurotoxic effects. In the present study, we found that n-3 polyunsaturated fatty acids can inhibit both microglial activation and dopaminergic injury in the substantia nigra of Sprague-Dawley rats induced by lipopolysaccharide, one of the major constituents of the outer membrane of Gram-negative bacteria. Moreover, n-3 polyunsaturated fatty acids inhibited lipopolysaccharide-induced activation of nuclear factor-κB, an important transcription factor involved in microglial activation. Taken together, our results provided the first in vivo evidence that n-3 polyunsaturated fatty acids can inhibit the damage of dopaminergic neurons induced by lipopolysaccharide through their inhibitory effects on nuclear factor-κB-dependent microglial activation.