Autism spectrum disorders usually present at a time of high synaptic plasticity, which has been thought to be mediated by the amount of zinc present. A recent study determined whether zinc deficiency affects the development of autism.
Autism spectrum disorders (ASD) present symptoms in children as early as three years old. These years are important for plasticity, which is the brain’s ability to readjust its synaptic connections based on the internal and external environment. Synaptic connections are the junctions between nerve cells, allowing nerve cells to communicate with each other and send signals throughout the body.
Shank proteins are scaffolding proteins that connect different kinds of receptors in the plasma membrane to the cytoskeleton of the cells. In particular, Shank proteins help regulate a subunit of AMPA receptors (AMPAR), which are receptors that respond to glutamate. They also help the formation of the synapses.
During the early years of child development, genes associated with ASD are proteins that are located in the synapses and are associated with development, for example, the Shank family of proteins. Shank2 and Shank3 are specifically of interest as they are located in excitatory synapses. It has further been found that prenatal zinc deficiency reduces the expression level of Shank2 and Shank3.
Therefore, Ha and colleagues investigated the effects of zinc on pathways that are regulated by Shank proteins, such as the composition of AMPAR subunits, and its influence on synaptic development. If a zinc deficiency affects the function of these Shank proteins, there would be abnormalities in the development of the associated to the synapses, which can in turn progress to the development of ASD. They published their results in Frontiers in Molecular Neuroscience.
They found that neurons from the hippocampus of young rats showed a subunit switch in AMPAR that was dependent on the amount of zinc that was present. They also found that Shank proteins were important mediators in the regulation for the composition of subunits that make up the AMPARs.
Further, they found that zinc affected the location and activity of both Shank proteins and AMPARs. When there was increased zinc, there was a subunit switch. In particular, zinc increased the time that synaptic currents mediated by AMPARs took to decay. Therefore, these currents would decay a lot faster if there was no zinc, decreasing the plasticity of these excitatory neurons.
Therefore, since they found significant zinc sensitivity in young neurons, and that these are dependent on Shank proteins the researchers suggest that zinc plays an important role in the development of autism spectrum disorders.
Written by Unaisa Bhayat, BMedSc
Reference: Ha H. T. T., Leal-Ortiz S., Lalwani K., Kiyonaka S., Hamachi I., Mysore S. P., Montgomery J. M., Garner C. C., Huguenard J. R., Kim S. A. Shank and Zink Mediate an AMPA Receptor Subunit Switch in Developing Neurons. Frontiers in Molecular Neuroscience. 2018; 405(11).