NeuroReport Volume 12, number 4, 733-737
Retrograde degeneration of neurite membrane structural integrity of nerve growth cones following in vitro exposure to mercury.
Christopher C.W. Leong, Naweed I. Syed, and Fritz L. Lorscheider
Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
This study showed that mercury can cause neurodegeneration in the brain central ring ganglia of the snail Lymnaea stagnalis. The resultant defective microtubule assembly and the aggregation of neurofibrils observed can also be found in the brains of Alzheimer’s patients. However, the species difference between snail cells and human cells does not necessarily provide a direct link between chronic exposure to mercury vapor and Alzheimer’s.
In dentistry the most commonly used material for fillings today is amalgam. Low concentrations of mercury vapor are constantly released from these amalgam fillings, accounting for 70% of mercury ions found in human urine. There have been several clinical studies over recent years, which have reported altered neurobehavior in dental personnel and this may well be due to chronic exposure to low level mercury vapor.
Growth cones are found at the tip of developing and regenerating neurons and play an important role in the development and maintenance of the neuron. The scaffolding of the growth cone is mainly made up of proteins called microtubules. Microtubules are composed of molecules called tubulin, which in pairs, join together in a process called polymerization to form a long-chained structure, which is ultimately a microtubule.
Using time-lapse photography with microscopy, the authors observed the microtubule structure at the growth cone in the brain neurons from the snail. The concentrations of mercury used were of the same order of magnitude as those reported in human and animal brains after chronic exposure to mercury vapor. Within a few minutes of exposure to mercury, the growth cone lost its motility and even exhibited robust collapse and retraction. The bare fibers of the neuron eventually formed aggregates. Over a 2-year period in over 40 different cultures, it was found that an average of 77% nerve growth cones were affected by exposure to mercury ions.
When neurons were exposed to the heavy metals aluminum, lead, cadmium and manganese, there was no observed degeneration of the growth cones. The collapsed growth cones were also stained for actin/tubulin immunofluorescence. Mercury treated growth cones exhibited a high disintegration of the microtubule structure compared with controls indicating that it was most probably this part of the growth cone that is affected by the mercury ions resulting in growth cone collapse.
To look at the extent of this effect of mercury on the growth cones, the authors then measured the total neural outgrowth over a 48-hour period in both control and mercury treated neurons. Less than 5% of neurons that were treated with mercury showed some sort of outgrowth in comparison with just over 93% of control neurons which displayed robust outgrowth.
The chronic exposure to mercury may be a potential factor in neurodegeneration in humans that could ultimately be observed as altered behavior.