Impact of Zinc Deficiency on Autism Spectrum Disorders
Understanding Autism Spectrum Disorders
Autism spectrum disorders (ASD) typically manifest in children as early as three years of age. These formative years are crucial for synaptic plasticity, which is the brain’s capability to adapt its synaptic connections in response to both internal and external stimuli. Synaptic connections serve as junctions between nerve cells, facilitating communication and signal transmission throughout the body.
The Role of Shank Proteins
Shank proteins are essential scaffolding proteins that link various types of receptors in the plasma membrane to the cytoskeleton of cells. Notably, they play a significant role in regulating a subunit of AMPA receptors (AMPAR), which respond to the neurotransmitter glutamate, and are involved in synapse formation. During early childhood development, genes associated with ASD, including the Shank family of proteins, are located in synapses and are crucial for normal development. Shank2 and Shank3, in particular, are noteworthy as they are found in excitatory synapses.
Zinc Deficiency and Shank Proteins
Recent findings indicate that prenatal zinc deficiency can diminish the expression levels of Shank2 and Shank3. In light of this, Ha and colleagues aimed to explore how zinc impacts pathways regulated by Shank proteins, including the composition of AMPAR subunits and their role in synaptic development. If zinc deficiency disrupts the function of these proteins, it may lead to abnormalities in synaptic development, potentially contributing to the onset of ASD. Their research results were published in Frontiers in Molecular Neuroscience.
Research Findings
The study revealed that neurons from the hippocampus of young rats exhibited a subunit switch in AMPAR, which was influenced by zinc levels. The researchers discovered that Shank proteins are critical mediators in regulating the composition of AMPAR subunits. Additionally, zinc was found to impact the location and activity of both Shank proteins and AMPARs. Increased zinc levels resulted in a subunit switch, enhancing the duration of synaptic currents mediated by AMPARs. Conversely, a lack of zinc accelerated the decay of these currents, thereby reducing the plasticity of excitatory neurons.
Conclusion
Given the significant sensitivity of young neurons to zinc and the dependence of these neurons on Shank proteins, the researchers propose that zinc plays a vital role in the development of autism spectrum disorders.
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 Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons. Frontiers in Molecular Neuroscience. 2018; 405(11).