Glutamate

BY Chutiya Chitboonthaweesuk, Phornnattha Kongsatitphan, Tanyarat Saelor

EDITED BY Pakpol Kunopasvorakul

Glutamate is a neurotransmitter, which are “chemical messengers” and their job is to send messages between nerve cells (neurons) in people’s brain. Glutamate is the most abundant excitatory neurotransmitter released by nerve cells in your brain. Neurons release glutamate in response to an experience or any kind of new information. Glutamate plays a major role in learning, especially through repetition or conditioning. With each repeated exposure, glutamate stimulates the same neurons, which reinforces the same neural pathways and helps you retain the information that have been exposed to. It also helps to encode memories in your brain, both short-term and long-term memory. Moreover, glutamate transmits pain across the nervous system to the brain and also stimulates taste receptors.

Potential Conditions and their Causes

For your brain to function properly, glutamate needs to be present in the right concentration in the right places at the right time. Excess glutamate in the brain is believed to cause the following conditions: 

• Brain injury

• Excessive activation of gland receptors might excite nerve cells to their death causing further brain injury.

• Alzheimer's disease

• Alzheimer’s disease is a progressive disease starting with mild memory loss and might possibly lead to loss of the ability to be responsive or carry on conversation with others. Glutamate is responsible for learning and memory. With unwanted excess amounts of glutamate, it could affect one’s memory.

• Parkinson's disease

• Parkinson’s disease is a progressive disorder that affects the nervous system and the parts of the body controlled by nerves. The loss of nigral dopaminergic neurons and the subsequent striatal depletion of dopamine in PD leads to glutamate overactivity which can damage nervous tissue.

• Huntington's disease

• Huntington’s disease is caused by NMDA receptors in cells that are over activated by glutamate. 

• Multiple sclerosis

• An excessive amount of glutamate overactivity its cellular receptors and induces cell death, causing a missing link between inflammatory and neurodegenerative processes evident in multiple sclerosis.

• Amyotrophic lateral sclerosis (ALS) 

• ALS can be caused by an increase in the releasing of glutamate or an impaired glutamate uptake. 

• Human immunodeficiency virus

• Human immunodeficiency virus or shortened as HIV is a virus in which attacks the body’s immune system. Glutamate plays a role in supporting HIV-1 replication, with higher concentrations of glutamate can lead to a higher change of the replication of the virus.

• Chronic pain and fatigue syndrome

• As glutamate is involved in central sensitization, which is associated with chronic pain, high levels of glutamate potentially contribute to the development or maintenance of central sensitization, causing chronic pain. Moreover, alterations in the levels of neurotransmitter systems, including glutamate, disrupt normal communication between neurons, which contribute to further pain and fatigue syndrome.

However, glutamate deficiency in the brain is also thought to be related to certain health conditions, including mainly mood disorders: 

• Major depressive disorder (MDD)

• Depressive disorder is associated with low glutamate levels in the brain or less sensitive glutamate receptors, meaning that even if the person receives more glutamate, the receptors would have trouble taking  it in.

• Schizophrenia

• For people with schizophrenia, glutamate receptors are not able to do their jobs.

• Glutamate formiminotransferase deficiency 

• It is a rare genetic disorder caused by low glutamate which results in mental and physical development delays.

Risk factors

Excess glutamate in one’s brain could happen from the following actions: 

• Having too little amount of GABA. Since GABA is formed through the process of the conversion of glutamate, with little amounts of GABA could elevate the glutamate levels. 

• Too much glutamate is released by nerve cells.

• High levels of glutamate can also be caused by too much glutamate that is directly released from glial cells. 

• Excess glutamine remains in the synapse which can lead to too many glutamate receptors being continuously activated and overexcited. 

• Nerve cell receptors have become overly sensitive to glutamine, meaning fewer levels of glutamate are needed to excite them leaving many leftover glutamate.

Glutamate deficiency can often be seen in relation to imbalance in other neurotransmitters, such as GABA as they work together to maintain the balance of the neurotransmitters’ excitatory and inhibitory effects. Glutamate can be turned into GABA by the enzyme glutamic acid decarboxylase (GAD), the process of glutamate conversion requires amino acids such as Taurine synthesis and vitamin B6. Hence, having low levels of Taurine and vitamin B6 could lead to having an imbalanced amount of glutamate.

Treatment

Excess level of glutamate treatment

1. Practice yoga and meditation

• Yoga and meditation practice stimulate GABA production, which has an effect to counterbalance the effect of excess glutamate.

1. Take a taurine supplement 

• Taurine acts similarly to GABA and blocks excitability in neurons. Taurine helps calm the nervous system down and prevent further damage from excess glutamate.

1. Dietary changes

• Some dietary factors can influence glutamate levels. For example, avoiding or reducing the intake of foods high in monosodium glutamate (MSG) may be beneficial. However, the relationship between dietary glutamate and brain glutamate levels is complex and varies from person to person.

Low levels of glutamate treatment

1. Exercise

• Around 10 - 15 minutes of exercise help increase glutamate levels, which also continue to rise for 15 - 20 minutes after exercise.

1. Drink coffee or other caffeinated beverages 

• Caffeine stimulates the brain to produce and release more glutamate.

1. Avoid drinking alcohol

• Alcohol slows the production of glutamate and the release of the neurotransmitter. 

1. Psychotherapy

• For conditions like depression or anxiety associated with low glutamate levels, psychotherapy or counseling may be beneficial. Cognitive-behavioral therapy (CBT) and other therapeutic approaches can address underlying psychological factors contributing to neurotransmitter imbalances.

These approaches, tailored to individual needs, can help maintain a healthy balance of glutamate, promoting overall well-being. Always consult with healthcare professionals before making significant lifestyle or supplement changes.

Works cited:

"Glutamate." Cleveland Clinic, https://my.clevelandclinic.org/health/articles/22839-glutamate 

"What Is Glutamate?" Verywell Health, https://www.verywellhealth.com/what-is-glutamate-5188294 

"11 Medical Conditions Associated with Glutamate Imbalance." Rupa Health, 

https://www.rupahealth.com/post/11-medical-conditions-associated-with-glutamate-imbalance#:~:text=Since%20GABA%20and%20Glutamate%20have,total%20amount%20in%20your%20brain.