Sabbar, M., Delaville, C., Deurwaerdère, P., et al (2012). Lead intoxication induces noradrenaline depletion, motor nonmotor disabilities, and changes in the firing pattern of subthalamic nucleus neurons. Neuroscience 210: 375-383 Details
Customer study highlights
The neurotoxic effects of heavy metals in humans and animals are well established. Lead, a common environmental pollutant, displaces calcium and is stored in bone. From there it enters the bloodstream and easily crosses the blood brain barrier. It is known to alter brain function by interfering with a number of neurotransmitter systems, particularly glutamate, and can cause Parkinsonian-like symptoms.
Parkinson’s disease is manifested by motor and non-motor deficits. The motor deficits are due to selective loss of dopaminergic (DA) neurons in the basal ganglia (BG). The subthalamic nucleus (STN), the major excitatory input to the BG, shows characteristic changes in firing in animal models of Parkinson’s disease (PD). Non-motor deficits are largely due to loss of noradrenergic neurons.
Prompted by epidemiological findings that occupational lead exposure doubles the risk of developing PD, this study compared rats given lead acetate (20 mg/kg/day) for 3 weeks (n=10) with control rats (n=10). Behavioral tests, extracellular neuronal recordings using a Neurolog amplifier and PowerLab, and biochemical assays were performed.
Rats placed in the ‘elevated plus’ maze normally spend around 40% of their time exploring exposed areas. Lead exposure reduced this to 10%, indicative of increased anxiety. However lead-exposed rats did not exhibit depressive-like behaviour, a common feature in PD sufferers. Lead toxicity induced profound motor deficits but, in contrast to PD, this effect was not coupled to a loss of DA neurons.
While there was no change in DA content, noradrenaline levels in the frontal cortex were reduced. Furthermore, similar to animal models of PD, glutamatergic neurons in the STN from lead-exposed rats exhibited a change from normal, regular firing to an irregular, burst-firing pattern.
Taken together, lead toxicity induces PD-like symptoms largely via noradrenergic neurons, accounting for certain non-motor effects, and influences neuronal firing patterns in the STN, accounting for motor deficits.