Getting to Know GABA
Preparing for your CNS exam? We’re going to do a bit of a deep dive into GABA, an inhibitory neurotransmitter, and highlight what you need to know for the exam! There’s more here than you need to know for the exam, so look for the 📚Takeaways for the CNS Exam.
What is GABA?
GABA, which is a cute little nickname for Gamma-Aminobutyric Acid, is an incredibly important chemical that is both an amino acid and a neurotransmitter for the body’s nervous system.
You’ll see in physiology that it is described as the “primary inhibitory neurotransmitter in the brain and a major inhibitory neurotransmitter in the spinal cord”.
Functionally, it is a neurotransmitter, but the structure is that of an amino acid. You’ll sometimes see it called an “amino acid neurotransmitter”. (Source)
So what does that mean?
📚Takeaways for the CNS Exam:
Inhibitory: it prevents neurons from releasing neurotransmitters. Essentially, it inhibits neurotransmission. Like a blanket gently draped over an oil fire. 🧘♀️
High levels of GABA = calming effects
Low levels of GABA = excitatory effects / increased anxiety
GABA Synthesis:
GABA, in its specific role as a key inhibitory neurotransmitter, is synthesized from glutamate, another neurotransmitter, through a process catalyzed by the enzyme glutamate decarboxylase (GAD).
The GAD enzyme is expressed only in cells that use GABA as a neurotransmitter. This enzyme requires vitamin B6 (pyridoxal phosphate) as a cofactor.
📚Takeaway for the CNS exam: to make GABA available as a neurotransmitter, we need glutamate and B6. Glutamate is an excitatory neurotransmitter = Like water poured on an oil fire. 🔥
Note that GABA can also be synthesized from glucose, which is metabolized to glutamate by the tricarboxylic acid cycle enzymes. Pyruvate and glutamine can also act as precursors. (Source)
Recycling: the GABA Shunt
The GABA shunt is a closed-loop process with the dual purpose of producing and conserving the supply of GABA. (Source)
Breakdown:
GABA is degraded by the enzyme GABA-transaminase into succinate semialdehyde which then enters the citric acid cycle. GABA-T deficiency is a rare inherited enzyme deficiency disorder. I don’t think you need recycling and breakdown info for the CNS exam. (Source)
Symptoms of Low GABA are many, and overlap with symptoms of general anxiety issues. From: Trudy Scott (Source)
Anxiety and feeling overwhelmed or stressed
Feeling worried or fearful / Fear of heights (and other situation-specific fears)
Panic attacks
Unable to relax or loosen up
Stiff or tense muscles
Feeling stressed and burned-out
Craving carbs, alcohol, or drugs for relaxation and calming
A few other side notes:
Low progesterone can contribute to low GABA; progesterone promotes relaxation because it promotes GABA
GABA (usually as Rx medication Gabapentin) is used for nerve pain
📚Takeaway for the CNS Exam: remember that GABA soothes the nervous system. Remember that progesterone promotes relaxation due to its impact on GABA.
Common Medications to Be Aware of:
Gabapentin (synthetic GABA)
Benzodiazepines (these psychiatric meds enhance the effect of GABA)
GABA-Transaminase inhibitors: (inhibit the breakdown of GABA, to increase circulating GABA)
Ex: valproic acid, vigabatrin, and phenylethylidenehydrazine, are GABA-T inhibitors used to treat epilepsy
Brexanolone (indirectly increases GABA) - for postpartum depression
📚Takeaway for the CNS Exam:
most medications are working to increase GABA through one of several mechanisms. More GABA = almost always the goal. (Except in a benzo overdose, where emergency meds are used to decrease GABA.)
Supplements:
GABA can be taken as a supplement, and has been shown to reduce anxiety, usually within 5-15 minutes of taking it. Sublingual or liposomal forms are recommended.
Historically, it was believed that oral GABA could not cross the blood brain barrier, but more recent evidence suggests it may cross the BBB in very small amounts, or cause a reduction of symptoms through some other way. TLDR: it is unclear if oral GABA can actually cross the blood-brain barrier, but it is clear that it has an impact on anxiety. (Source)
📚Takeaways for the CNS exam:
GABA can likely cross the BBB, but if this question is on the exam and it implies that it cannot cross the BBB, contest it!
The evidence is not super clear cut, so I would argue that we don’t have enough information - and we don’t know how up to date the CNS exam content is on this particular topic. (I was taught in school in 2017 ish that GABA did not cross the BBB, but that has since been very seriously debated.)
Food Sources:
We can consume GABA from food, primarily:
Cruciferous vegetables
Many legumes (soy, lupin, adzuki, peas)
Tomato
Spinach
Sweet potatoes
Mushrooms (especially shimeji mushrooms like white beech - bunshimeji and bunapi)
Whole grains (buckwheat, oat, wheat, barley, rice)
GABA Brown Rice (sprouted brown rice, which contains higher levels of GABA)
You can make GABA rice at home by soaking and sprouting yourself, and you can even buy special rice cookers that have a GABA rice setting to help simplify the soaking, sprouting, and cooking process.
📚Takeaway for the CNS exam: GABA is widely available in food and can be made in the body; dietary analysis is not likely to yield much information about a person’s GABA status.
We can also convert GABA from the excitatory neurotransmitter (and amino acid) glutamate. Sources of glutamate are usually foods high in umami (monosodium glutamate) such as tomato paste, dried fish or fish sauce, caviar, aged cheese, fermented soy products, mushrooms, aged meat, as well as spinach. (Source)
📚Takeaway for the CNS exam: Copper inhibits conversion of glutamate to GABA via the enzyme glutamate decarboxylase. Watch for copper excess and keep zinc and copper in balance.
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