GABA and Glutamate and Their Role in HD

Posted: May 1, 2013 in Uncategorized
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Remember that Huntington’s Disease is a genetic, degenerative disorder that leads to an increased expansion of the polyglutamine tract called the CAG repeat.  Along with this CAG repeat disorder, people with HD experience excitotoxicity.  In this article I am going to discuss the role that GABA and glutamate play in this part.

Glutamate is our major excitatory neurotransmitter.  It is the chemical messanger that tells us to GO.  GABA is its anithesis as it is our major inhibitory neurotransmitter.  When we release glutamate and all signals are go, GABA then becomes released to calm everything back down and bring us back to homeostasis.  GABA and glutamate activate ionotrophic and metabotropic receptors.

Metapotropic receptors are also known as G-Protein Coupled receptors.  These receptors are the most abundant receptors found in the central nervous system.  In fact, drug companies are looking at drugs that interact with these receptors to aid in the treatment of HD (

Chorea is one of the early symptoms associated with HD.  This is the involuntary movements that the patients suffer from.  The hypothesis is that decreased GABA leads to the chorea seen in HD (  Some studies also show an excess of dopamine in the basal ganglia, the area of the brain affected in HD (  GABA is needed for inhibition of dopamine.  Also, glutamate and dopamine need to be in balance for proper function.

Studies have found there to be an increase in both dopamine and glutamate in the symptoms of HD and that perhaps balancing them out would have a therapeutic benefit (  Inhibition of glutamate has been found in autopsies of HD patients.  This would lead to increased receptor sensitivity to glutamate and it directly correlates with CAG expansion size (  The CAG expansion is a polyglutamine tract.  Perhaps the increased sensitivity in the receptors is leading to an increase in CAG repeats? 

When cells exhibit too much excitotoxicity the mitochondria of the cell will send a message to destroy the cell.  This may be the cause of neurodegeneration seen in HD.  Some theories state that mitochondrial dysfunction is at the center of cell death in HD.  There may be normal amounts of glutamate present, but the mitochondria reads it inappropriately and sends the message to destroy the cell (

The take away from this is we need to address the balance of neurotransmitters to offset the symptoms associated with HD.  A balance of dopamine, glutamate, and GABA are essential to neuroprotection.  Also, a diet that is high in nutrients such as N-acetyl-cysteine, coenzyme Q10, B vitamins, magnesium, and others is essential to maintaining mitochondrial health.


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