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| “Never go to excess, but let moderation be your guide.” (Marcus Tullius Cicero) |
Moderation and balance is the key
to living a healthy lifestyle. Drinking wine is
good for your health, however too much can prove to be fatal. Medicine should always be taken with care as
to not overdose and cause more harm to the patient. Dr.
Jane Flinn of the Department of Psychology at George Mason University has done
extensive research on the role of metals in behavior and physiology. More specifically, her research is focused on
the roles of zinc (Zn), copper (Cu), and iron (Fe) in learning, memory,
Alzheimer’s, and macular degeneration.
Have a cold or the flu? Take a zinc supplement and your recovery rate
will accelerate! But users beware, too
much may actually make you more sick. Zinc is
a mineral that is essential to cellular metabolism and immune functions. Since the human body does not have a
specialized storage system for Zn, supplements are available for daily
intake. A lack of Zn could lead to deficits
in taste, hindered growth, anemia, and a weakened immune system. However, just because too little is bad, too
much is not necessarily good. Dr. Flinn’s
research suggests that too much Zn can actually harm learning and memory. Excessive Zn results in a Cu deficiency, which
is associated with a reduction in myelination in the brain. High amounts of Zn have been found in the
hippocampus, amygdala, and prefrontal regions of the brain. Thus, Zn affects spatial memory, a function
of the hippocampus, and fear conditioning, a function of the amygdala and
prefrontal cortex. Although the effects of Zn deficiency have been thoroughly researched on, there are few studies that focus on
the effects of elevated Zn in the brain.
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| Zinc is essential to maintaining health, but too much zinc can have negative effects. |
In order to investigate the role of Zn in memory and
Alzheimer’s, Dr. Flinn manipulated Zn dosages in rats and evaluated their
performance in subsequent memory tasks.
The rats were fed Zn-fortified water that also contained Cu and Fe (10
ppm Zn, 0.25 ppm Cu, and 10 ppm Fe).
Controls were given regular lab water.
The rats were then placed in a Morris Water Maze
(MWM) and Stationary Atlantis Platform to test their spatial and reference memory. Three and nine month latencies were measured
to assess the effects of elevated levels of Zn in the rats. After three months, compared to the controls,
rats that were fed with Zn-fortified water were significantly slower when
learning how to find the submerged platform in the MWM and Stationary Atlantis
Platform. At nine months, the same Zn-fortified
rats were much worse at remembering where the platform was located in the tasks
and were more anxious during the task.
The results suggested that increased levels of Zn in the rats’ brains
impaired their spatial and reference memory.
In the lab, mice were also raised to carry an APP mutation so that they developed Alzheimer’s-like plaques. Dietary enhancements of Zn (10 ppm ZnCO3) were administered to the mice and they were then placed in a MWM. The Zn-fortified mice that had Alzheimer’s-like plaques showed impaired spatial memory. The elevated level of Zn along with the onset of Alzheimer’s proved to be detrimental to spatial memory performance.
Fear conditioning (FC) was also evaluated in relation to elevated levels of Zn. There are two parts to fear
conditioning: fear acquisition and fear
retention. New learning must take place
to learn that a stimulus is no longer fearful and as a result, the fear becomes extinguished. The mice were placed in boxes for six minutes and a 20-second tone was
given at the end of three, four, and five seconds.
During the last two seconds of the tone, a shock was administered to
implement delayed conditioning. The mice
were tested on contextual (same box but no tone) and cued (different box with
tone but no shock) fear conditioning extinction. The results showed the Zn enhanced mice froze
more and had a slower fear extinction rate, so the levels of Zn and extinction
rate were negatively correlated.
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| Depiction of FC and extinction. From left to right: Training, Cued FC extinction, and Contextual FC extinction. |
In both experiments, which evaluated spatial memory and fear
learning, the impairments were alleviated by giving the animals small amounts
of Cu. Post-traumatic stress disorder
(PTSD) is characterized by the unnecessary retention of fear, which was modeled
by the mice mentioned above. Individuals
with PTSD are unable to learn that certain stimuli are no longer fearful and cannot extinguish
their fears. How can the common basis of
fear extinction in Zn-fortified animals and patients with PTSD help develop a
new treatment for PTSD? Possibly in the
future, Cu supplements can be tweaked and modified to be used as a treatment
for PTSD. Furthermore, supplementation with
copper remediated the effects of increased Zn levels in mice that modeled
Alzheimer’s disease. With these
findings, the use of dietary supplements with Zn should be monitored in the
elderly population, since they are already at risk for Alzheimer’s. Increasing Zn consumption with the intention
of improving health could backfire and have detrimental effects if the dosage
is not controlled. The research discussed above examined the role of Zn in memory, which can be broadly applied to other illnesses as well, such as dementia, anxiety disorders, depression, and mild cognitive impairment. However, as the field of medical science continues to advance in drug development, we must evaluate whether these drugs are causing more harm than help.
