Glutamate: The Master Neurotransmitter and Its Implications in Chronic Stress and Mood Disorders

Summary & key facts

This short review says glutamate is a key brain chemical that helps nerve cells talk, and it has big effects on memory, thinking, and mood. The paper explains how chronic stress can disturb glutamate and reduce the brain's ability to adapt. It reviews studies showing that some drugs that change glutamate can quickly lift severe depression, while simple things like exercise and mindfulness also change glutamate levels a little and may help mood and thinking. The author stresses that many details are still unknown and more research is needed.

Key facts:

• Glutamate is the brain's main excitatory chemical messenger. That means it helps turn on nerve cells and is central to learning, memory, and mood.
• The brain must keep glutamate at the right level. Too little can sap energy, and too much can damage or kill cells.
• Glutamate helps the brain change its wiring, a process called neuroplasticity. This includes strengthening connections for memory and weakening them when needed.
• Chronic stress changes glutamate differently in different brain areas. In the memory area called the hippocampus, stress can raise glutamate and shrink parts of nerve cells, which links to memory problems.
• In the thinking and attention area called the prefrontal cortex, chronic stress can lower glutamate and reduce connections, which may hurt attention and planning.
• Stress can also activate immune-like brain cells called microglia, which increase inflammation and may damage the brain's plasticity.
• A review of blood studies found higher glutamate levels in people with major depression compared with people without depression.
• Some drugs that affect glutamate act fast. Low-dose ketamine can ease depressive symptoms quickly, often within a few hours, and a single intravenous dose has reduced suicidal thoughts within a day in pooled trials.
• Other glutamate-targeting drugs have had mixed results. For example, a drug called rapastinel briefly looked promising but later failed to beat placebo in trials.
• Non-drug actions like vigorous exercise and mindfulness can modestly raise brain glutamate and the calming chemical GABA. One study found levels rose by about 5 percent and stayed up for at least 30 minutes after hard exercise.

Abstract

This brief review article makes the argument that glutamate is deserving of its newfound attention within the neuroscience literature and that many directions of important research have yet to be explored. Glutamate is an excitatory neurotransmitter with several types of receptors found throughout the central nervous system, and its metabolism is important to maintaining optimal levels within the extracellular space. As such, it is important to memory, cognition, and mood regulation. The mechanisms by which chronic stress affect the glutamatergic system and neuroplasticity are outlined. Several implications for potential pharmacologic and non-pharmacologic interventions are discussed.

Topics

Anesthesia and Neurotoxicity Research Neuroscience and Neuropharmacology Research Treatment of Major Depression

Categories

Cellular and Molecular Neuroscience Life Sciences Neuroscience

Tags

Affect (linguistics) Central nervous system Cognition Communication Dopamine Excitatory postsynaptic potential Glutamate receptor Glutamatergic Inhibitory postsynaptic potential Internal medicine Medicine Mood Neuroplasticity Neuroscience Neurotransmitter Neurotransmitter Agents Neurotransmitter systems Psychiatry Psychology Receptor

Substances

Ketamine

Conditions & symptoms

Anxiety Depression Anxiety or worry Difficulty focusing Lack of energy or motivation Sadness or low mood