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,
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
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
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
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.