Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

Figure 2

Interaction between glia and neurons may lead to neuron damage and death. LPS activates microglia from a resting state to an activated one, probably through the CD14 and the TLR4 receptors; this signalling pathway, mediated by different molecular adaptors, kinases, and MAP kinases, activates NF-κB with the consequent transcription of specific genes leading to microglial activation. Then, activated microglial cells release several compounds, as proinflammatory cytokines, radical oxygen species (ROS), and NO that may eventually lead to neuronal death. Within dopaminergic neurons, the mitochondrial respiratory chain can be affected by several substances, leading to energy failure, production of ROS, and reduction of the neurons viability. ROS can act as signal for the activation of microglia, indicating that neurons are not healthy. DA can exert a toxic action through the ROS formed in its oxidative metabolism; it may also forms complexes with cysteine, inhibiting the respiratory chain and producing more ROS. The reduction/elimination of microglial induction could ameliorate neuronal damage.