GABA and glutamate: The balancing act of the nervous system

As with most things in life, balance is key to an optimally functioning nervous system.  GABA and glutamate are the primary calming and excitatory neurotransmitters in the central nervous system (respectively) and serve opposing functions.  Despite their opposite roles, GABA and glutamate have many connections, including their existence in the same biological pathway (Figure 1).

Figure 1. Glutamate is the biological precursor for GABA.  Glutamate is synthesized from the nonessential amino acid glutamine, and glutamate is converted into GABA by the enzyme glutamate decarboxylase.  Glutamate decarboxylase uses Vitamin B6 as a cofactor.

Figure 1. Glutamate is the biological precursor for GABA. Glutamate is synthesized from the nonessential amino acid glutamine, and glutamate is converted into GABA by the enzyme glutamate decarboxylase. Glutamate decarboxylase uses Vitamin B6 as a cofactor.

Under normal physiological conditions, glutamate and GABA activity is in balance.  However, under stressful conditions, such as inflammation or immune upregulation, glutamate activity increases.  If the nervous system is functioning appropriately, GABA activity also increases to compensate for the excitation in an attempt to restore homeostasis.

Glutamate is the precursor to GABA, which means an increase in glutamate levels should cause a subsequent increase in GABA synthesis as well (Figure 2).  This “allostatic mechanism” is the body’s attempt to restore homeostasis and balance excitatory and compensatory activity.  Common symptoms of an imbalanced system in which glutamate levels are more elevated than GABA levels include anxiousness, overstimulation, sleep difficulties, and focus issues.

Figure 2. GABA should increase in activity to compensate for elevations in stimulatory neurotransmitters, such as glutamate, under stressful conditions.

Figure 2. GABA should increase in activity to compensate for elevations in stimulatory neurotransmitters, such as glutamate, under stressful conditions.

How do glutamate and GABA become out of balance though?  There are a variety of factors that can prevent glutamate from converting to GABA.  One of the most common is malnutrition or poor diet.  Without an adequate amount of Vitamin B6 in their diet, or poor absorption of B6 in the GI tract, there may not be enough necessary cofactor for the glutamate decarboxylase enzyme to facilitate the conversion to GABA.  Another possible contributor to inadequate conversion is gluten sensitivity.  Gluten sensitivity creates gliadin antibodies which specifically inhibit the glutamate decarboxylase enzyme.  Without the functional enzyme, GABA synthesis is compromised, which can lead to low GABA levels.

Regardless of the cause, imbalances between glutamate and GABA can lead to symptoms.  For a healthy and optimally functioning nervous system, GABA and glutamate balance is essential. Even though GABA is the most calming neurotransmitter in the central nervous system, and glutamate the most excitatory, they are irreversibly linked as part of the same biochemical pathway and balance is key.

References
Cryan, J.F., et al. (2005). Don’t worry ‘B’ happy!: a role for GABAb receptors in anxiety and depression. TRENDS in Pharmacological Sciences, 26(1): 36-43.
Dong, E., et al. (2012). Effects of microinjections of Group II metabotropic glutamate agents into the amygdala on sleep. Brain Res, 1452: 85-95.
Hadjivassi, R., et al. (2004). Gluten sensitivity: from gut to brain. Trends in Immunology, 11: 578-82.
Nikolaus, S., et al. (2010). Cortical gaba, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders-results from in vivo imaging studies. Reviews in the neurosciences, 21(2): 119-39.
This entry was posted in Neurology and tagged , , , , , , . Bookmark the permalink.

4 Responses to GABA and glutamate: The balancing act of the nervous system

  1. Tammy Manor says:

    What can be done to increase GABA if one is gluten sensitive? Are the gliadin antibodies present even when one is not eating gluten?

    • Sarah Mo says:

      A good way to help restore GABA levels in this situation is to simply avoid gluten. If someone with a gluten sensitivity is continually exposed to gluten the immune system will stay on high alert by producing antibodies. These gliadin antibodies that affect the conversion of glutamate to GABA will decrease over time if gluten is being not being ingested, and most will be out of your system within 6 to 9 months.

  2. Pingback: Gaba Soothe30 Vcaps | Tuổi trung niên

  3. cyu says:

    Really clear explanation THANKS!

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s