Prenatal Lipopolysaccharide Alters Postnatal Dopamine in the Laboratory Rat

Evidence links both genetic factors and environmental toxins to the development of PD. Although a genetic basis accounts for some cases of PD, the vast majority of PD is idiopathic and therefore of unknown etiology. Other environmental factors including exposure to viruses (post-encephalitic PD) and consumption of foods thought to contain excitotoxins (ALS-PD-Dementia Complex of Guam) have also been proposed. In the mid-1980s the involvement of environmental DA neurotoxins in PD was brought into focus when drug abusers inadvertently consumed a synthetic heroin eventually found to contain the DA specific neurotoxin MPTP. As a result Calne and Langston1 hypothesized that an environmental neurotoxin in combination with normal aging was responsible for PD. They proposed that toxin exposure killed DA neurons, but that the DA neuron loss was not, by itself, sufficient to bring the affected patient to the symptom threshold in a normal life span (symptom threshold is widely believed to be loss of ~80% of the striatum’s DA and ~50% of the DA neurons in the substantia nigra compacta (SNc)). They thus proposed that normal age-related losses of DA neurons resulted in further DA neuron loss sufficient to produce PD symptoms. In some respects this hypothesis has been borne out since abusers who took large dosages of MPTP developed symptoms within a week while others exposed to lower dosages, developed symptoms years later. This has led most investigators supporting the involvement of environmental toxins as risk factors in PD to study middle-life events.