Targeting the noradrenergic system for anti-inflammatory and neuroprotective actions in an animal model of Parkinson's disease

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder that is characterised by the selective loss of dopamine (DA) neurons within the substantia nigra pars compacta and results in reduced striatal DA input culminating in motor dysfunction characteristic of Parkinsonian disorders. Much of our understanding of the pathologies underlying PD have been obtained from neurotoxin-based animal models such as the 6-hydroxydopamine (6-OHDA) model. In addition, neuroinflammation is now recognised as a key contributor to the progression of many chronic neurodegenerative disorders such as PD, Alzheimer's disease and multiple sclerosis and is driven by the activation of glial cells, particularly microglia. As such, the bacterial endotoxin and inflammatory stimulus lipopolysaccharide (LPS) may be used to induce degeneration of DA neurons in the substantia nigra to model the inflammatory changes observed in PD.