Why Zinc is so important?

  Dr. Jane Flinn of the Department of Psychology at George Mason University talked about the importance of metals in behavior and physiology. Her main focus was in the roles of zinc, copper, and iron in learning, memory, and Alzheimer’s.

Zinc Pills

Many of us limit our thinking that calcium is the only important metal in neuroscience, but lets talk about another equally important metal called zinc.  Zinc is heavily involved in learning and memory and are found in ca3 region of hippocampus. One of the ways zinc operates in our body is by decreasing copper level, therefore it can cause copper deficiency induced by high level of zinc, which can affect neuronal conduction. People with macular degeneration have blobs in their eyes, which are filled with zinc. Taking zinc can slow down the rate of progression of macular degeneration however it depletes the copper in the body. Hence, high level of zinc can cause copper deficiency and copper deficiency can result in anemia. Therefore, it is important to know how much of zinc is needed in our body to function properly. The role of Zinc in our body is significant because it is involved in the immune system, thus a zinc deficiency can lead to cognitive impairment. It is high in the brain, retina, and in the prostate. It is found in the brain areas in the hippocampus, the amygdala, and the prefrontal region.

Morris Water Maze (MWM)

The Morris water maze is a maze where rats can use cues to spatially learn to swim.  Mice model were compared between wild type and transgenic mice carrying the ApoE 4 gene, and human version of amyloid precursor protein (hAPP). These mice were given different level of zinc, copper, and iron in their drinking water. They experimented that zinc and iron are heavily involved in spatial memory because mice model with early onset AD showed impaired spatial memory. In addition, increased zinc diminishes the ability to learn when a cue is no longer seemed to be fearful in normal mice and rats.

Fear conditioning is when a neutral stimulus is paired with a conditioned stimulus, so the purpose in this experiment was to eliminate the fear of the neutral stimulus. Learning that a stimulus is no longer fearful is called extinction. Fair conditioning depends on the amygdala and prefrontal regions (extinction), which is highly dependent on zinc. An experiment was done to measure impairments in fear extinction. In this experiment, animals were put in a box for 6 minutes. A tone was ringed and a shock was given at the end of 3^rd minute. This was repeated three times. The next day animals were given the same environment however no tone or shock was given. Then the following day, animals were put in slightly different environments to change the appearance of the floor and bedding to see if animals believe the box is dangerous or not. The result showed that zinc enhanced mice took longer to learn fear extinction and showed memory deficit, therefore there is a negative correlation between the level of zinc and extinction rate.

Consequently, this study makes us aware about how much of zinc we should consider in our dietary supplement to avoid copper deficiency and anemia. Also, knowing that zinc is highly involved in memory, could we use zinc to slow the progression of disorders such dementia, stress, and cognitive impairment?

An alpha7/Gprin1 Interaction

Images of At nAChR and Gprin1

Jacob Nordman, a Ph.D. candidate working in the Kabbani Lab of the Krasnow Institute at George Mason University spoke on his research on α7 nicotinic acetylcholine receptor (nAChR) and G protein regulated-inducer of neurite outgrowth 1 (Gprin1) interactions which regulates axon growth and growth cone within hippocampal neurons. The α7 nAChR is a ligand gated calcium channel, which are abundantly expressed within the developing and adult hippocampus. 

 The main focus of this research includes the goal to study the proteome and their relation to dopamine and nicotinic acetylcholine receptors in the nervous system.  Studying their relation is significant in brain functioning such as memory, and cognition that could furthermore help us to understand of developing drugs for the treatment of several brain disorders like Alzheimer’s disease, Parkinson’s disease, and Schizophrenia.

The structure of the Growth Cone

 Nordman explained the Ionotropic and metabotropic division, and their study between the interaction of α7 and Gprin1. He then focused his topic on the growth cone that plays critical role in guiding axonal development and wiring of neuronal circuit. It is a complex structure of three layers: central zone (forearm), transitional zone (palm of hand) and peripheral (fingers). Together they make up arm, which pulls the growth cone along to its final destination that guides axon development. The seven states that take place in axonal development are initiation, formation, guidance, branching, turning, arrest and retraction.

Molecular model of the alpha7 nicotinic receptor.

His research have found that α7and Gprin1 are enriched in the soma and growth cones. To prove the interaction of α7 and Gprin1 in growth cones, transfection was done to insert α7 nAChR into Neuro-2a cells, which are neuron-like cells that produce only Gprin1, followed by immunoprecipitation, in which Gprin1 was removed from Neuro-2a cells. As a result of removing Gprin1, the link between α7  nAChR and Gprin1 was weakened, suggesting that they are present in growth cones and have interaction between two.

Consequently Nordman concluded his presentation that in “active state” filopodia of the growth cone project in all direction. It commits to a direction through microtubule invasion of collapse of filopodia. α7 activation inhibits G proteins mediated pathways involved in growth. The sum effect is microtubule capping and growth cone collapse.

 

Hence, these findings contribute in helping us to understand signaling cascades, new drug targets, plasticity mechanisms, greater-inter connectivity and many more functions we have not discovered yet. As a result, this makes us wonder that since α7and Gprin1 on the growth cone plays critical role in guiding axonal development and wiring of neuronal circuit, could it play greater role in treating or curing neurological disorders?